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WO2024227919A1 - Procédé de réduction du taux de conversion alimentaire chez un animal d'élevage - Google Patents

Procédé de réduction du taux de conversion alimentaire chez un animal d'élevage Download PDF

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Publication number
WO2024227919A1
WO2024227919A1 PCT/EP2024/062257 EP2024062257W WO2024227919A1 WO 2024227919 A1 WO2024227919 A1 WO 2024227919A1 EP 2024062257 W EP2024062257 W EP 2024062257W WO 2024227919 A1 WO2024227919 A1 WO 2024227919A1
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Prior art keywords
mmo
sialylated
animal
fucosylated
administered
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Inventor
Joeri Beauprez
Ut VAN NGUYEN
Annelies VERCAUTEREN
Mariska VAN DE VOSSE
Jordi LENSINK
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Inbiose NV
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Inbiose NV
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/10—Feeding-stuffs specially adapted for particular animals for ruminants
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/30—Feeding-stuffs specially adapted for particular animals for swines
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/60—Feeding-stuffs specially adapted for particular animals for weanlings

Definitions

  • the present invention relates to a method to reduce the feed conversion ratio (FCR) of a farmed animal.
  • FCR feed conversion ratio
  • Feed for a farmed animal such as cattle, pigs and poultry, constitutes more than 60% of the total farm expenses.
  • increasing the feed efficiency has a strong influence on financial returns for farmers.
  • a fucosylated mammalian milk oligosaccharide (MMO) and/or a sialylated MMO can decrease the feed conversion ratio (FCR) of a farmed animal.
  • FCR feed conversion ratio
  • a fucosylated MMO and a sialylated MMO results in an unexpected and strong reduction of the FCR of a farmed animal.
  • Said fucosylated MMO and said sialylated MMO are not associated with adverse effects and are safe to use in farmed animals.
  • the first aspect of the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering (i) a fucosylated mammalian milk oligosaccharide, (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • FCR feed conversion ratio
  • the second aspect of the invention provides the use of (i) a fucosylated mammalian milk oligosaccharide, (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide to reduce the FCR of a farmed animal.
  • the third aspect of the invention provides a method to increase the body weight of a farmed animal, wherein said method comprises the step of administering a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide a fucosylated mammalian milk oligosaccharide
  • a fucosylated mammalian milk oligosaccharide a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide; and wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide
  • the invention provides a method of feeding a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide; and wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide
  • the inventors have surprisingly found that a method according to the invention significantly reduces the FCR of a farmed animal, even when fed ad libitum.
  • feed conversion ratio is the ratio between the feed intake of a farmed animal in a given period divided by its weight gain calculated over the same period.
  • FCR is the inverse of "feed efficiency” (i.e. 1/FCR).
  • the expression “reduce the feed conversion ratio” can be interchangeably used with “increase the feed efficiency”.
  • a farmed animal has a lower FCR (and hence a higher feed efficiency) if the animal produces either a greater body mass with the same feed intake or the same body mass with less feed intake.
  • the body weight of a farmed animal can be readily assessed by an appropriate and dedicated scale, depending on the nature of the farmed animal. As assessing the weight of a farmed animal is imperative for animal performance, tracking estimated profits and calculating feed efficiency, all commercial farms have agricultural scales readily available and in use. Examples for large animals (e.g. cattle, horse, sheep) include platform/floor scales and pen-type scales (single animal scales). For smaller animals (e.g. calves, lambs, goats) farm bar scales are suitable. For poultry, bench scales (weighing a single bird), floor/platform scales and hanging scales (weighing a group of birds) are available.
  • large animals e.g. cattle, horse, sheep
  • pen-type scales single animal scales
  • For smaller animals e.g. calves, lambs, goats farm bar scales are suitable.
  • bench scales weighing a single bird
  • floor/platform scales and hanging scales weighing a group of birds
  • the feed intake of a farmed animal can also be readily assessed by the skilled person.
  • the animal is individually housed.
  • a group of animals is housed together.
  • each animal can be individually identified so that the disappearance of feed can be directly linked to the correct animal.
  • Systems for assessing the feed intake of a farmed animal are readily available: for example cattle (Bloch et al, 2021, Animal 15(7); Calan gate; GrowSafe Feed Intake and Behavioural Measurement System), pigs (Maselyne et al, 2015, Physiol. Behav. 138: p.
  • any known method to assess FCR can be suitably used. While not a prerequisite, it is preferred that the body weight and feed intake of the farmed animal is assessed using the same methods on the first day and last day of said period.
  • said FCR is calculated over a given period, wherein said period is 2 weeks, more preferably 3 weeks, even more preferably 4 weeks, even more preferably 5 weeks, even more preferably 6 weeks, even more preferably 8 weeks, even more preferably 10 weeks, most preferably 12 weeks.
  • said FCR is calculated over a period which corresponds with 25.0%, preferably 50.0%, more preferably 75.0, most preferably 100.0%, of the total period wherein the oligosaccharide(s) according to the invention is/are administered to the farmed animal (it is in this context referred to the Section "Method to reduce FCR").
  • a farmed animal receives a fucosylated MMO according to the invention for a period of 12 weeks
  • the FCR is preferably calculated over a period of 3 weeks (i.e. 25.0%), more preferably 6 weeks (i.e. 50.0%), even more preferably 9 weeks (i.e. 75%) and most preferably 12 weeks (i.e. 100.0%).
  • the method according to the invention reduces the FCR of a farmed animal with at least 1.0 %, 2.0 %, 3.0 %, 4.0 %, 5.0 %, 6.0 %, 7.0 %, 8.0 %, 9.0 % or 10.0 %, preferably relative to said FCR of said animal prior to administration of i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention.
  • said FCR reduces with at least 2.0 %, more preferably at least 2.5 %, even more preferably at least 3.0 %, even more preferably at least 3.5 %, even more preferably at least 4.0 %, even more preferably at least 4.5 %, even more preferably at least 5.0 %, most preferably at least 7.0 %.
  • the term "reduces the FCR” can be replaced with "increases the feeding efficiency" and vice versa.
  • a farmed animal has a FCR of 2.30 just before the onset of administering i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention, and the FCR on the last day of administration is 2.17 (for example after 12 weeks), than it can be concluded that the method according to the invention has reduced the FCR of said farmed animal with 5.7 % after a treatment lasting 12 weeks.
  • the method according to the invention reduces the FCR of a farmed animal with at least 1.0 %, 2.0 %, 3.0 %, 4.0 %, 5.0 %, 6.0 %, 7.0 %, 8.0 %, 9.0 % or 10.0 %, preferably relative to the FCR of a control farmed animal that did not receive the administration of i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention.
  • said FCR reduces with at least 2.0 %, more preferably at least 2.5 %, even more preferably at least 3.0 %, even more preferably at least 3.5 %, even more preferably at least 4.0 %, even more preferably at least 4.5 %, even more preferably at least 5.0 %, most preferably at least 7.0 %.
  • said FCR is calculated over a period which corresponds with:
  • - if subject is a pig 3 weeks, preferably 4 weeks, more preferably 5 weeks, even more preferably 6 weeks, even more preferably 8 weeks, even more preferably 10 weeks, most preferably 12 weeks;
  • - if subject is a goat 6 weeks, preferably 8 weeks, more preferably 10 weeks, most preferably 12 weeks;
  • - if subject is a horse 6 weeks, preferably 8 weeks, more preferably 10 weeks, most preferably 12 weeks;
  • - if subject is a camelid 6 weeks, preferably 8 weeks, more preferably 10 weeks, most preferably 12 weeks;
  • subject is a rabbit: 6 weeks, preferably 8 weeks, more preferably 10 weeks, most preferably 12 weeks;
  • - if subject is a fish or a crustacean 1 week, preferably 2 weeks, more preferably 3 weeks, even more preferably 4 weeks, even more preferably 5 weeks, even more preferably 6 weeks, even more preferably 8 weeks, even more preferably 10 weeks, most preferably 12 weeks;
  • subject is poultry: 6 weeks, preferably 8 weeks, more preferably 10 weeks, most preferably 12 weeks.
  • the reduction of the feed conversion ratio in a farmed animal by the method according to the invention is independent from the presence/absence and/or severity of diarrhea in said farmed animal. In other words, a reduction of diarrhea in the farmed animal is not a prerequisite to obtain a reduction of the feed conversion ratio by a method according to the invention.
  • each embodiment disclosed in the context wherein the subject is a horse is also disclosed for a subject being a donkey, a mule or a hinny.
  • said method is to reduce the feed conversion ratio of a farmed animal.
  • a "farmed animal” refers to an animal that is reared in an agricultural setting in order to produce various commodities such as food (meat, organs, eggs, dairy products) and/or hair or wool.
  • said farmed animal is an animal that is reared in an agricultural setting in order to produce food, in particular meat.
  • a farmed animal is preferably selected from the list consisting of bovine, pig, sheep, goat, horse, donkey, mule, hinny, camelid (preferably llama or alpaca), rabbit, fish, crustacean and poultry; more preferably selected from the list consisting of bovine, pig, sheep, goat, horse, camelid (preferably llama or alpaca), rabbit, fish, crustacean and poultry; more preferably selected from the list consisting of bovine, pig, sheep, goat, horse, camelid (preferably llama or alpaca), rabbit, fish and poultry; even more preferably selected from the list consisting of bovine, pig, sheep, goat, horse, camelid (preferably llama or alpaca) and poultry; even more preferably selected from the list consisting of bovine, pig, sheep, goat, camelid (preferably llama or alpaca) and poultry; even more preferably selected from the list consisting of bovine, pig, sheep, goat, camelid (preferably llama or alpac
  • a farmed animal is preferably selected from the list consisting of bovine and pig, most preferably said farmed animal is a bovine.
  • the term "poultry” refers to birds bred by humans for their eggs, meat and/or feathers.
  • said poultry preferably is a chicken, a quail, a turkey, a duck, a pigeon and a goose, more preferably a chicken, a quail or a turkey, more preferably chicken or a quail, most preferably a chicken.
  • the term “chicken” is preferably replaced with broiler.
  • said animal is a multigastric animal, preferably a ruminant or camelid, more preferably a ruminant.
  • said camelid is a llama or an alpaca, more preferably said camelid is an alpaca.
  • said ruminant is selected from the list consisting of bovine, sheep and goat, more preferably said ruminant is bovine.
  • said animal is a monogastric animal, preferably selected from the list consisting of pig, horse, rabbit, fish and poultry, more preferably selected from the list consisting of pig, horse, rabbit and poultry, even more preferably selected from the list consisting of pig, horse and poultry, even more preferably pig or horse, most preferably pig.
  • the terms "subject” and “animal” can be preferably replaced with "subject in the need thereof” and "animal in the need thereof", respectively.
  • said animal according to the invention is a non-adult animal.
  • said animal according to the invention is a young animal. Throughout the application and claims, unless specifically stated otherwise, a "non-adult animal" can be preferably replaced with "juvenile animal” or "young animal”.
  • a non-adult bovine is a calf; a non-adult pig is a piglet; a non-adult sheep is a lamb; a non-adult goat is a kid; a non-adult horse is a foal; a non-adult llama is a cria; a non-adult alpaca is a cria; a non-adult rabbit is a kitten or a kit; a non-adult fish is a fry (young fish which is capable of feeding himselfj/fingerling (young fish which is capable of feeding himself and has developed scales and working fins, i.e. transition to a juvenile fish is complete), preferably a fingerling; a non-adult poultry/chicken is a chick.
  • said animal according to the invention is a preweaned animal.
  • said animal according to the invention is an animal that is weaned.
  • weaning refers to the process of withdrawing the access of a young animal to milk and to gradually accustom the young animal to the adult diet.
  • said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide e.g., a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • a “fucosylated mammalian milk oligosaccharide (MMO)” refers to a MMO that comprises a fucose.
  • said fucosylated MMO according to the invention contains only one fucose, i.e. said MMO consists of two or more monosaccharides and only one of said monosaccharides is a fucose.
  • a “sialylated mammalian milk oligosaccharide” refers to a MMO that comprises a sialic acid, preferably a N-acetylneuraminic acid (i.e. Neu5Ac).
  • said sialylated MMO according to the invention contains only one sialic acid (preferably only one Neu5Ac), i.e. said MMO consists of two or more monosaccharides and only one of said monosaccharides is a sialic acid (preferably a Neu5Ac).
  • mammalian milk oligosaccharides comprise oligosaccharides present in milk found in any phase during lactation including colostrum milk from humans (i.e. human milk oligosaccharides or HMOs) and mammals including but not limited to cows (Bos Taurus), sheep (Ovis aries), goats (Capra aegagrus hircus), bactrian camels (Camelus bactrianus), horses (Eguus ferus caballus), pigs (Sus scropha), dogs (Canis lupus familiaris), ezo brown bears (Ursus arctos yesoensis), polar bear (Ursus maritimus), Japanese black bears (Ursus thibetanus japonicus), striped skunks (Mephitis mephitis), hooded seals (Cystophora cristata), Asian elephants (Elephas
  • cows Bos Taurus
  • sheep
  • milk oligosaccharides comprise N-acetyllactosamine (Gal-pi,4-GlcNAc) or lacto-N-biose (Gal-pi,3-GlcNAc) at the reducing end (Urashima et al, 2011; Wrigglesworth et al, 2020, PLoS ONE 15(12); Urashima et al, 2013, Biosci. Biotechnol. Biochem 77(3): p. 455-466; Wei et al, 2018, Sci. Rep. 8:4688).
  • N-acetyllactosamine Gal-pi,4-GlcNAc
  • lacto-N-biose Gal-pi,3-GlcNAc
  • Examples hereof are 3-FLN (Gal- pi,4-(Fuc-al,3-)GlcNAc; also known as Lewis x antigen), 3'-SLN (Neu5Ac-a2,3-Gal-pi,4-GlcNAc), 6'-SLN (Neu5Ac-a2,6-Gal-pi,4-GlcNAc) (Urashima et al, 2011; Wrigglesworth et al, 2020; Wei et al, 2018). Further, milk saccharides comprise milk glycosaminoglycans (GAGs; Coppa et al, 2013; Rai et al, 2021, Int. J. Biol.
  • Antigens of the human ABO blood group system such as the A determinant (GalNAc-alphal,3(Fuc-alphal,2)-Gal), B determinant (Gal-alphal,3(Fuc-alphal,2)-Gal) and H-determinant (Fuc-alphal,2-Gal) have been shown to be present in saccharides of the milk of mammals (e.g. A tetrasaccharide in a lion and leopard; Wrigglesworth et al, 2020).
  • MMO mammalian milk oligosaccharide
  • HMO human milk oligosaccharide
  • oligosaccharide preferably refers to a saccharide containing 2 up to and including 20 monosaccharides, i.e. the degree of polymerization (DP) is 2-20, more preferably refers to a saccharide containing 3 up to and including 20 monosaccharides, i.e. the degree of polymerization (DP) is 3-20.
  • the term “oligosaccharide” preferably refers to a saccharide consisting of 2-20, more preferably 3-20, monosaccharide units which are linked to each other via glycosidic bonds in a linear or in a branched structure.
  • the linkage (i.e. glycosidic linkage), between two sugar units, i.e. two monosaccharides, can be expressed, for example, as 1,4, l->4, or (1-4), which are used interchangeably herein.
  • an oligosaccharide as described herein consists of 3-8, even more preferably 3-7, even more preferably 3-6, most preferably 3-5, monosaccharides.
  • x-y refers to a range from and including x to and including y.
  • 3-5 monosaccharides means that 3, 4 or 5 monosaccharides are present.
  • the method according to the invention comprises the step of administering to said farmed animal a fucosylated mammalian milk oligosaccharide (MMO).
  • MMO fucosylated mammalian milk oligosaccharide
  • said fucosylated MMO is a neutral oligosaccharide.
  • a "neutral" oligosaccharide as used herein and as generally understood in the state of the art is an oligosaccharide that has no negative charge originating from a carboxylic acid group.
  • said fucosylated MMO consists of 3-8, more preferably 3-7, even more preferably 3-6, most preferably 3-5, monosaccharides.
  • said fucosylated MMO comprises a fucose that is linked to a monosaccharide in an alpha-1,2-, alpha-1,3- or alpha-1, 4-linkage, preferably an alpha-1,2- or an alpha-1, 3-linkage, more preferably an alpha-1, 2-linkage, and wherein said monosaccharide is preferably selected from glucose, N-acetylglucosamine and galactose, more preferably said monosaccharide is glucose or galactose, even more preferably said monosaccharide is galactose.
  • fucose is linked to a monosaccharide refers to the situation wherein the fucose is bound to a monosaccharide through a glycosidic bond and wherein said fucose and monosaccharide are part of the oligosaccharide of the invention (which can comprise additional monosaccharide(s) than said fucose and said monosaccharide).
  • said fucosylated mammalian milk oligosaccharide comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, preferably said fucosylated oligosaccharide comprises lactose or LacNAc at is reducing end, more preferably said fucosyalted oligosaccharide comprises lactose at its reducing end.
  • a fucosylated MMO comprising lactose at its reducing end is preferably selected form the list consisting of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3-FL), difucosyllactose (diFL), lacto-N-fucopentaose I (LNFP I), blood group A antigen hexaose type 1 (GalNAc-LNFP I), blood group B antigen hexaose type 1 (Gal-LNFP I), lacto-N-fucopentaose II (LNFP 11), lacto-N-fucopentaose III (LNFP III), lacto-N-fucopentaose V (LNFP V), lacto-N-difucohexaose I (LNDFH I), lacto-N-difucohexaose II (LNDFH II), lewis b-lewis
  • a fucosylated MMO comprising lacto-N-biose (LNB) at its reducing end is preferably selected form the list consisting of 2'-fucosyllacto-N-biose (2'FLNB), 4-fucosyllacto-N-biose (4FLNB) and difucosyllacto-N-biose (diFLNB), more preferably wherein said fucosylated mammalian milk oligosaccharide is 2'FLNB or diFLNB, most preferably wherein said fucosylated mammalian milk oligosaccharide is 2'FLNB.
  • 2'FLNB 2'-fucosyllacto-N-biose
  • 4FLNB 4-fucosyllacto-N-biose
  • diFLNB difucosyllacto-N-biose
  • a fucosylated MMO comprising N-acetyllactosamine (LacNac) at its reducing end is preferably selected form the list consisting of 2'-fucosyl-N-acetyllactosamine (2'FlacNAc), difucosyl-N-acetyllactosamine (diFLacNAc) and 3-fucosyl-N-acetyllactosamine (3FlacNAc), more preferably wherein said fucosylated mammalian milk oligosaccharide is 2'FlacNAc or diFLacNAc, most preferably wherein said fucosylated mammalian milk oligosaccharide is 2'FlacNAc.
  • said fucosylated MMO according to the invention is selected from a list consisting of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3-FL), difucosyllactose (diFL), 2'-fucosyl-N- acetyllactosamine (2'FlacNAc), difucosyl-N-acetyllactosamine (diFLacNAc), 3-fucosyl-N-acetyllactosamine (3FlacNAc), 2'-fucosyllacto-N-biose (2'FLNB), 4-fucosyllacto-N-biose (4FLNB), difucosyllacto-N-biose (diFLNB), lacto-N-fucopentaose I (LNFP I), blood group A antigen hexaose type 1 (GalNAc-LNFP I), blood group B antigen hexa
  • said fucosylated MMO according to the invention is selected from the list consisting of 2'FL, diFL, LNFP I, GalNAc-LNFP I, Gal-LNFP I, LNDFH I, lewis b-lewis x, DFLNH (a), TFLNH, LNnFP I, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from the list consisting of 2'FL, diFL, LNFP I, LNnFP I, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from the list consisting of 2'FL, diFL, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from the list consisting of 2'FL, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from the list consisting of 2'FL, 2'FLNB
  • the method according to the invention does not exclude the administration of one or more additional mammalian milk oligosaccharides, albeit it is not a prerequisite to achieve a reduction of the feed conversion ratio of a farmed animal.
  • the method according to the invention comprises the administration of a fucosylated MMO as described herein and one or more sialylated MMO's, more preferably a fucosylated MMO as described herein and two or more sialylated MMO's, even more preferably a fucosylated MMO as described herein and two sialylated MMO's, as depicted further herein.
  • said fucosylated MMO is the sole MMO administered to said farmed animal according to the method of the invention.
  • a fucosylated MMO refers to at least one fucosylated MMO, preferably to one fucosylated MMO (i.e. no further fucosylated MMO's).
  • the method according to the invention comprises the step of administering to said farmed animal a sialylated mammalian milk oligosaccharide (MMO), preferably two or more sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's are administered; preferably administered as a mixture), more preferably two sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO as described herein; preferably administered as a mixture).
  • MMO sialylated mammalian milk oligosaccharide
  • the expression "more preferably two sialylated MMO's" in this context of the invention means that no additional sialylated MMO's are administered to the subject. It was surprisingly found in the present invention, that administering a sialylated MMO, in particular the combination of 3'-sialyllactose (3'SL) and 6'- sialylalactose (6'SL), preferably no additional sialylated MMO's are administered, to a farmed animal results in a strong decrease of the feed conversion ratio of said animal, albeit to a lesser extent than administering a fucosylated MMO as described earlier herein.
  • the method according to the invention comprises the step of administering to a farmed animal:
  • a sialylated MMO preferably two or more sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's), more preferably two sialylated MMO(s) (i.e. a first sialylated MMO and a second sialylated MMO); or
  • a fucosylated MMO and a sialylated MMO preferably a fucosylated MMO and two or more sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's), more preferably a fucosylated MMO and two sialylated MMO(s) (i.e. a first sialylated MMO and a second sialylated MMO).
  • said fucosylated MMO is as described earlier herein.
  • administering a sialylated MMO in a method according to the invention further comprises administering a second sialylated MMO (preferably no further sialylated MMOs).
  • said sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2,3-, alpha-2,6- or alpha-2, 8- linkage, preferably an alpha-2,3- or an alpha-2, 6-linkage, and wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine, even more preferably said monosaccharide is galactose.
  • a sialic acid preferably a Neu5Ac
  • sialic acid is linked to a monosaccharide
  • sialic acid refers to the situation wherein the sialic acid is bound to a monosaccharide through a glycosidic bond and wherein said sialic acid and monosaccharide are part of the oligosaccharide of the invention (which can comprise additional monosaccharide(s) than said sialic acid and said monosaccharide).
  • said sialylated MMO consists of 3-8, more preferably 3-7, even more preferably 3-6, most preferably 3-5, monosaccharides.
  • said sialylated MMO comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, preferably said sialylated MMO comprises lactose or LacNAc at is reducing end, most preferably said sialylated MMO comprises lactose at its reducing end.
  • LNB lacto-N-biose
  • LacNAc N-acetyllactosamine
  • a sialylated MMO comprising lactose at its reducing end is preferably selected from the list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6-disialyllactose, 6,6'-disialyllactose, 8,3-disialyllactose, 3'S- 2' FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c and LST d; more preferably selected from the list consisting of 3'SL, 6'SL, 3,6-disialyllactose, 6,6'-disialyllactose, 8,3-disialyllactose, LST a, LST b, LST c and LST d; even more preferably selected from the list consisting of 3'SL, 6'SL, L
  • a sialylated MMO comprising lacto-N-biose (LNB) at its reducing end is preferably selected form the list consisting of 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB) and monofucosylmonosialyllacto-N-octaose (sialyl Lewis a); more preferably said sialylated MMO is 3'SLNB or 6'SLNB.
  • a sialylated MMO comprising N-acetyllactosamine (LacNac) at its reducing end is preferably selected form the list consisting of 3'-sialyllactosamine (3'SLacNAc), 6'-sialyllactosamine (6'SLacNAc) and sialyl Lewis x; more preferably said sialylated MMO is 3'SLacNAc or 6'SLacNAc.
  • said sialylated MMO according to the invention is selected from a list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6-disialyllactose, 6,6'-disialyllactose, 8,3- disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), sialyl Lewis a, 3'-sialyllactosamine (3'SLacNAc), 6'- sialyllactosamine (6'SLacNAc) and sialyl Lewis x.
  • sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x. Even more preferably said sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'SLNB, 6'SLNB, 3'SLacNAc and 6'SLacNAc. Most preferably said sialylated MMO is 3'-sialyllactose (3'SL) or 6'-sialyllactose (6'SL).
  • said first sialylated MMO according to the invention is selected from a list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6- disialyl lactose, 6,6'-disialyllactose, 8,3-disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), sialyl Lewis a, 3'-sialyllactosamine (3'SLacNAc), 6'-sialyllactosamine (6'SLacNAc) and sialyl Lewis x.
  • said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x. Even more preferably said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'SLNB, 6'SLNB, 3'SLacNAc and 6'SLacNAc.
  • first sialylated MMO is 3'-sialyllactose (3'SL) or 6'-sialyllactose (6'SL), most preferably said first sialylated MMO is 3'SL.
  • said second sialylated MMO according to the invention is selected from a list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6- disialyl lactose, 6,6'-disialyllactose, 8,3-disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), monofucosylmonosialyllacto-N- octaose (sialyl Lewis a), 3'-sialyllactosamine (3'SLacNAc), 6'--
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'SLNB, 6'SLNB, 3'SLacNAc and 6'SLacNAc. Even more preferably said second sialylated MMO is 6'-sialyllactose (6'SL) or 3'-sialyllactose (3'SL), most preferably said second sialylated MMO is 6'SL.
  • the method according to the invention does not exclude the administration of one or more additional mammalian milk oligosaccharides, albeit it is not a prerequisite to achieve a reduction of the feed conversion ratio of a farmed animal.
  • the method according to the invention comprises the administration of one or more sialylated, preferably two or more sialylated, more preferably two sialylated, MMO's as described herein and a fucosylated MMO as depicted herein.
  • said sialylated MMO('s) is/are the sole MMO('s) administered to said farmed animal according to the method of the invention.
  • a sialylated MMO refers to one or more sialylated MMO's, preferably to two or more sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's), more preferably to two sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO and no further sialylated MMO's).
  • the method according to the invention comprises the step of administering to said farmed animal a fucosylated mammalian milk oligosaccharide (MMO) and a sialylated mammalian milk oligosaccharide (MMO), preferably a fucosylated MMO and two or more sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's are administered), more preferably a fucosylated MMO and two sialylated MMO's (i.e. a first sialylated MMO and a second sialylated MMO).
  • MMO fucosylated mammalian milk oligosaccharide
  • MMO sialylated mammalian milk oligosaccharide
  • the expression "more preferably two sialylated MMO's" in this context of the invention means that no additional sialylated MMO's are administered to the subject. It is preferred that the administered MMO's are administered as a mixture, more preferably as part of a composition, even more preferably as part of a composition according to Section "Composition".
  • the method according to the invention comprises administering a fucosylated MMO, a first sialylated MMO and a second sialylated MMO (preferably no further sialylated MMO's are administered).
  • said fucosylated MMO is as described earlier herein.
  • said first sialylated MMO is as said sialylated MMO as described earlier herein.
  • said second sialylated MMO is as said sialylated MMO as described earlier herein.
  • said first sialylated MMO is selected from the list consisting of 3'-sialyllactose (3'SL), 6'- sialyllactose (6'SL), 3,6-disialyllactose, 6,6'-disialyllactose, 8,3-disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), sialyl Lewis a, 3'-sialyllactosamine (3'SLacNAc), 6'-sialyllactosamine (6'SLacNAc) and sialyl Lewis x.
  • said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'S-2'FL, 6'S-2'FL, 3'S- 3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x. Even more preferably said first sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'SLNB, 6'SLNB, 3'SLacNAc and 6'SLacNAc. Even more preferably said first sialylated MMO is 3'-sialyllactose (3'SL) or 6'- sialyllactose (6'SL), most preferably said first sialylated MMO is 3'SL.
  • said second sialylated MMO is selected from the list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6-disialyllactose, 6,6'-disialyllactose, 8,3-disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3- FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'-sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), sialyl Lewis a, 3'-sialyllactosamine (3'SLacNAc), 6'-sialyllactosamine (6'SLacNAc) and sialyl Lewis x.
  • 3'-sialyllactose 6
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, LST a, LST b, LST c, LST d, 3'SLNB, 6'SLNB, sialyl Lewis a, 3'SLacNAc, 6'SLacNAc and sialyl Lewis x.
  • said second sialylated MMO is selected from the list consisting of 3'SL, 6'SL, 3'SLNB, 6'SLNB, 3'SLacNAc and 6'SLacNAc. Even more preferably said second sialylated MMO is 6'-sialyllactose (6'SL) or 3'-sialyllactose (3'SL), most preferably said second sialylated MMO is 6'SL.
  • said first sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2, 3-linkage, wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine.
  • said first sialylated MMO is preferably selected from the list consisting of 3'- sialyllactose (3'SL), 3'-sialyl-2'-fucosyllactose (3'S-2'FL), 3'-sialyl-3'-fucosyllactose (3'S-3'FL), LST a, LST d, 3'-sialyl-N-acetyllactosamine (3'SLacNAc), 3'-sialyl-3-fucosyllactose and 3'-sialyllacto-N-biose (3'SLNB), more preferably selected from the list consisting of 3'-sialyllactose (3'SL), LST a, LST d, 3'-sialyl-N- acetyllactosamine (3'SLacNAc) and 3'-sialyllacto-N-biose (3'SLNB), even more preferably selected
  • said second sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2, 6-linkage, wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine.
  • said second sialylated MMO is preferably selected from the list consisting of 6'-sialyllactose (6'SL), 6' -sialyl-2' -fucosyllactose (6'S-2'FL), 6' -sialyl-3' -fucosyllactose (6'S- 3'FL), Neu5Ac-a2,6-[GlcNAc-bl,3]Gal-bl,4-Glc, LST b, LST c, 6'-sialyl-N-acetyllactosamine (6'SLacNAc) and 6'-sialyllacto-N-biose (6'SLNB), more preferably selected from the list consisting of 6'-sialyllactose (6'SL), LST b, LST c, 6'-sialyl-N-acetyllactosamine (6'SLacNAc) and 6'-ssi
  • the method according to the invention does not exclude the administration of one or more additional mammalian milk oligosaccharides, albeit it is not a prerequisite to achieve a high reduction of the feed conversion ratio of a farmed animal.
  • the method according to the invention comprises the administration of a fucosylated MMO and a sialylated MMO as described herein. It is more preferred that the method according to the invention comprises the administration of a fucosylated MMO, a first sialylated MMO and a second sialylated MMO (preferably no additional sialylated MMO's are administered) as described herein.
  • said fucosylated MMO, said first sialylated MMO and said second sialylated MMO are the sole MMOs administered to said farmed animal according to the method of the invention.
  • Aforementioned fucosylated mammalian milk oligosaccharides are commercially available and/or the production/purification of these oligosaccharides has been described and hence allows the skilled person to produce/obtain any of said fucosylated oligosaccharides accordingly.
  • each reference is incorporated by reference:
  • sialylated mammalian milk oligosaccharides are commercially available and/or the production/purification of these oligosaccharides has been described and hence allows the skilled person to produce/obtain any of said sialylated oligosaccharides accordingly.
  • each reference is incorporated by reference:
  • 3'S-3-FL Biosynth / Cymit Quimica (3D-OSO1065)
  • Sialyl lewis a Carbosynth (OS00745)
  • said fucosylated MMO and/or said sialylated MMO, preferably said fucosylated MMO and said sialylated MMO, according to the invention has/have been isolated from a microbial cultivation or fermentation, cell culture, enzymatic reaction or chemical reaction.
  • said fucosylated MMO and/or said sialylated MMO, preferably said fucosylated MMO and said sialylated MMO, of the invention has/have been isolated by e.g. chromatography or filtration technology from a natural source such as a human or animal milk, preferably animal milk.
  • a solution can for example be obtained by a method comprising the steps of: (a) cultivating at least one cell as defined herein, preferably a single cell, that is capable to produce said fucosylated MMO, and/or said sialylated MMO, preferably said fucosylated MMO and said sialylated MMO, in a suitable cultivation medium to form a cultivation broth, preferably wherein said cell is metabolically engineered for the production of said fucosylated MMO and/or said sialylated MMO, preferably said fucosylated MMO and said sialylated MMO, and
  • clarifying the cultivation broth refers to the removal of suspended particulates and contaminants, particularly cells, cell components, insoluble metabolites and debris produced by culturing the cell according to the invention. Clarification is preferably one or more of centrifugation, flocculation, decantation and/or filtration.
  • removing salts and/or medium components form said clarified cultivation broth refers to removing substantially all the proteins, as well as peptides, amino acids, RNA and DNA and any endotoxins and glycolipids from said clarified cultivation broth, preferably after it has been.
  • proteins and related impurities can be removed from said saccharide in a conventional manner.
  • proteins, salts, by-products, colour, endotoxins and other related impurities are removed from said oligosaccharide by ultrafiltration, nanofiltration, two-phase partitioning, reverse osmosis, microfiltration, activated charcoal or carbon treatment, treatment with non-ionic surfactants, enzymatic digestion, tangential flow high-performance filtration, tangential flow ultrafiltration, electrophoresis (e.g. using slab-polyacrylamide or sodium dodecyl sulphate-polyacrylamide gel electrophoresis (PAGE)), affinity chromatography (using affinity ligands including e.g.
  • DEAE-Sepharose poly-L-lysine and polymyxin-B, endotoxin-selective adsorber matrices
  • ion exchange chromatography such as but not limited to cation exchange, anion exchange, mixed bed ion exchange, inside-out ligand attachment
  • hydrophobic interaction chromatography and/or gel filtration i.e., size exclusion chromatography
  • chromatography particularly by chromatography, more particularly by ion exchange chromatography or hydrophobic interaction chromatography or ligand exchange chromatography.
  • oligosaccharide With the exception of size exclusion chromatography, proteins and related impurities are retained by a chromatography medium or a selected membrane, said oligosaccharide remains in the said oligosaccharide containing clarified cultivation broth. Further purification of said oligosaccharide may be accomplished, for example, by use of (activated) charcoal or carbon, nanofiltration, ultrafiltration, electrophoresis, enzymatic treatment or ion exchange to remove any remaining DNA, protein, LPS, endotoxins, or other impurity. Alcohols, such as ethanol, and aqueous alcohol mixtures can also be used. Another purification step is accomplished by crystallization, evaporation or precipitation of the product.
  • Powder is preferably obtained by spray drying, freeze drying, spray freeze-drying, crystallization, lyophilization, band or belt drying, drum or roller drying, and/or agitated thin film drying, preferably by spray drying, drum or roller drying, or agitated thin film drying, more preferably by spray drying or agitated thin film drying, most preferably by spray drying, of a solution containing said oligosaccharide(s).
  • said oligosaccharide(s) according to the invention constitutes > 70.0 %, preferably > 75.0 %, more preferably > 80.0, (w/w) of said powder.
  • said powder contains ⁇ 15 wt. %, preferably ⁇ 10 wt. %, more preferably ⁇ 9 wt. %, more preferably ⁇ 8 wt. %, more preferably ⁇ 7 wt. %, even more preferably ⁇ 5 wt. %, even more preferably ⁇ 4 wt. % of liquid, even more preferably ⁇ 3 wt. % of liquid, even more preferably ⁇ 2 wt. % of liquid, most preferably ⁇ 1 wt. %, preferably wherein said liquid is water.
  • said fucosylated MMO according to the invention has been produced, preferably in vitro and/or ex vivo, by a cell, preferably a single cell, wherein said cell is preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell and a protozoan cell.
  • said fucosylated oligosaccharide of the invention has been produced by an in vitro and/or ex vivo culture of cells, wherein said cells are preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell or a protozoan cell.
  • said sialylated MMO according to the invention has been produced, preferably in vitro and/or ex vivo, by a cell, preferably a single cell, wherein said cell is preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell and a protozoan cell.
  • said sialylated oligosaccharide of the invention has been produced by an in vitro and/or ex vivo culture of cells, wherein said cells are preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell or a protozoan cell.
  • said cell is a microorganism.
  • said microorganism is selected from a list consisting of a bacterium, a yeast and a fungus.
  • said cell is genetically engineered for the production of said fucosylated MMO and/or sialylated MMO according to the invention.
  • the latter bacterium preferably belongs to the phylum of the Proteobacteria or the phylum of the Firmicutes or the phylum of the Cyanobacteria or the phylum Deinococcus-Thermus, preferably belongs to the phylum of the Proteobacteria.
  • the latter bacterium belonging to the phylum Proteobacteria belongs preferably to the family Enterobacteriaceae, preferably to the species Escherichia coli.
  • the latter bacterium preferably relates to any strain belonging to the species Escherichia coli such as but not limited to Escherichia coli B, Escherichia coli C, Escherichia coli W, Escherichia coli K12, Escherichia coli Nissle. More specifically, the latter term relates to cultivated Escherichia coli strains - designated as E. coli K12 strains - which are well-adapted to the laboratory environment, and, unlike wild type strains, have lost their ability to thrive in the intestine. Well-known examples of the E.
  • coli K12 strains are K12 Wild type, W3110, MG1655, M182, MC1000, MC1060, MC1061, MC4100, JM101, NZN111 and AA200.
  • the present invention specifically relates to a mutated and/or transformed Escherichia coli strain as indicated above wherein said E. coli strain is a K12 strain. More specifically, the present invention relates to a mutated and/or transformed Escherichia coli strain as indicated above wherein said K12 strain is E. coli MG1655.
  • the latter bacterium belonging to the phylum Firmicutes belongs preferably to the Bacilli, preferably from the species Bacillus, such as Bacillus subtilis or, B.
  • amyloliquefaciens Bacterium belonging to the phylum Actinobacteria, preferably belonging to the family of the Corynebacteriaceae, with members Corynebacterium glutamicum or C. afermentans, or belonging to the family of the Streptomycetaceae with members Streptomyces griseus or S. fradiae.
  • the latter yeast preferably belongs to the phylum of the Ascomycota or the phylum of the Basidiomycota or the phylum of the Deuteromycota or the phylum of the Zygomycetes.
  • the latter yeast belongs preferably to the genus Saccharomyces (with members like e.g.
  • Pichia with members like e.g. Pichia pastoris, P. anomala, P. kluyveri
  • Komagataella Hansunella
  • Kluyveromyces with members like e.g. Kluyveromyces lactis, K. marxianus, K. thermotolerans
  • the latter yeast is preferably selected from Pichia pastoris, Yarrowia lipolitica, Saccharomyces cerevisiae and Kluyveromyces lactis.
  • the latter fungus belongs preferably to the genus Rhizopus, Dictyostelium, Penicillium, Mucor or Aspergillus.
  • Plant cells includes cells of flowering and nonflowering plants, as well as algal cells, for example Chlamydomonas, Chlorella, etc.
  • said plant cell is a tobacco, alfalfa, rice, cotton, rapeseed, tomato, corn, maize or soybean cell.
  • the latter animal cell is preferably derived from non-human mammals (e.g.
  • cattle, buffalo, pig, sheep, mouse, rat birds (e.g. chicken, duck, ostrich, turkey, pheasant), fish (e.g. swordfish, salmon, tuna, sea bass, trout, catfish), invertebrates (e.g. lobster, crab, shrimp, clams, oyster, mussel, sea urchin), reptiles (e.g. snake, alligator, turtle), amphibians (e.g. frogs) or insects (e.g. fly, nematode) or is a genetically modified cell line derived from human cells excluding embryonic stem cells. Both human and non-human mammalian cells are preferably chosen from the list comprising an epithelial cell like e.g.
  • a mammary epithelial cell a mammary epithelial cell, mammary myoepithelial cell, mammary progenitor cell, an embryonic kidney cell (e.g. HEK293 or HEK 293T cell), a fibroblast cell, a COS cell, a Chinese hamster ovary (CHO) cell, a murine myeloma cell like e.g. an N20, SP2/O or YB2/0 cell, an NIH-3T3 cell, a non-mammary adult stem cell or derivatives thereof such as described in WO21067641, preferably mesenchymal stem cell or derivates thereof as described in WO21067641.
  • an embryonic kidney cell e.g. HEK293 or HEK 293T cell
  • a fibroblast cell a COS cell
  • a Chinese hamster ovary (CHO) cell a murine myeloma cell like e.g. an N20
  • Said insect cell is preferably derived from Spodoptera frugiperda like e.g. Sf9 or Sf21 cells, Bombyx mori, Mamestra brassicae, Trichoplusia ni like e.g. BTI-TN-5B1-4 cells or Drosophila melanogaster like e.g. Drosophila S2 cells.
  • the latter protozoan cell preferably is a Leishmania tarentolae cell.
  • said fucosylated MMO of the invention has been produced, preferably in vitro and/or ex vivo, by a mammary epithelial cell, mammary myoepithelial cell and/or mammary progenitor cell, preferably wherein said cell is generated from nonmammary adult stem cells, more preferably wherein said cell is generated from mesenchymal stem cells.
  • said sialylated MMO of the invention has been produced, preferably in vitro and/or ex vivo, by a mammary epithelial cell, mammary myoepithelial cell and/or mammary progenitor cell, preferably wherein said cell is generated from nonmammary adult stem cells, more preferably wherein said cell is generated from mesenchymal stem cells.
  • WO2021/067641 and WO2021/242866 mimmary epithelial cells derived from non-mammary adult stem cells, preferably from mesenchymal stem cells
  • WO2021/142241 mimmary epithelial cells, mammary myoepithelial cells, mammary progenitor cells.
  • said fucosylated MMO of the invention has been produced, preferably in vitro and/or ex vivo, by a microorganism cell, preferably said microorganism is a bacterium, a yeast or a fungus, more preferably said microorganism is a bacterium or a yeast, even more preferably said microorganism is a bacterium, most preferably said microorganism is Escherichia coli.
  • said sialylated MMO of the invention has been produced, preferably in vitro and/or ex vivo, by a microorganism cell, preferably said microorganism is a bacterium, a yeast or a fungus, more preferably said microorganism is a bacterium or a yeast, even more preferably said microorganism is a bacterium, most preferably said microorganism is Escherichia coli.
  • two or more different cells produce the fucosylated MMO and/or sialylated MMO according to the invention. It is however preferred that a single cell produces said oligosaccharide(s), i.e. a single culture of said cell produces the oligosaccharide(s) of the invention.
  • said fucosylated MMO according to the invention is linked, preferably chemically linked, to a carrier for delivery of said MMO.
  • said sialylated MMO according to the invention is linked, preferably chemically linked, to a carrier for delivery of said MMO.
  • said first sialylated MMO according to the invention is linked, preferably chemically linked, to a carrier for delivery of said MMO.
  • said second sialylated MMO according to the invention is linked, preferably chemically linked, to a carrier for delivery of said MMO.
  • said carrier is a ceramide-based carrier or a polypeptide-based carrier, more preferably said carrier is a ceramide-based carrier.
  • said polypeptide-based carrier is epsilon-polylysine, alfa- polylysine, poly(aspartic acid), polyglutamic acid or polyornithine. These carriers are commercially available (e.g. Sigma-Aldrich, Carbosynth).
  • Said ceramide-based carrier is preferably selected from a list consisting of dl8:l/16:0, tl8:0-16:0, tl8:0-hl6:0, tl8:0-h22:0 and tl8:0-h24:0.
  • These ceramide carriers are commercially available and well-known to the skilled person and are for example described in W02010/037785 which is incorporated by reference.
  • dl8:l/16:0 is also known as C16 ceramide and N- palmitoylsphingosine and therefore interchangeable used herein.
  • tl8:0-16:0 is also known as C16 phytoceramide and N-hexadecanoyl phytosphingosine and therefore interchangeable used herein.
  • tl8:0- hl6:0, tl8:0-h22:0 and tl8:0-h24:0 are glycosylinositolphosphoceramides (GIPCs).
  • GIPCs glycosylinositolphosphoceramides
  • d and t refer to the hydroxylation state of the whole ceramide or long-chain base moiety (d is 2 groups, t is 3 groups), whereas "h” denotes a hydroxylation of the fatty acyl group.
  • Said fucosylated mammalian milk oligosaccharide and optionally any, preferably all, further mammalian milk oligosaccharides is preferably encapsulated (i.e. forming an encapsulate).
  • This is particularly advantageous to protect said oligosaccharide(s) from conditions relating to the manufacturing or storing of a composition as described in the Section "Composition", especially when said composition is a nutritional composition (it is referred to the Section "Composition").
  • Such conditions typically entail a high pressure (e.g. a pressure of above 10 bar during extrusion), a high temperature (e.g.
  • a temperature above 100°C during extrusion and baking a pH lower than 5, a pH higher than 8, and/or a high moisture content (e.g. wet extrusion).
  • other molecules within a composition, especially a nutritional composition such as proteins could chemically interact with said fucosylated MMO (and any other further MMO if present) especially under the harsh conditions during manufacturing of a nutritional composition.
  • said "fucosylated MMO” is preferably replaced with "encapsulated fucosylated MMO". If any further MMO is present than it is preferred that all MMO's present in the composition are encapsulated, preferably all MMO's are co-encapsulated.
  • sialylated mammalian milk oligosaccharide or said sialylated MMO's and optionally any, preferably all, further mammalian milk oligosaccharides is preferably encapsulated (i.e. forming an encapsulate).
  • composition is a nutritional composition (it is referred to the Section "Composition) which is manufactured by extrusion (dry or wet, preferably wet).
  • the encapsulate is of the core-shell type, i.e. carrier material forms a shell around the active agent (i.e. the MMO('s) according to the invention), preferably wherein the core has a median diameter (D(v,0.5)) of 125-250 pm, preferably 150-250 pm, more preferably 165-250 pm, most preferably 165-225 pm, and wherein said encapsulate has a median diameter (D(v,0.5)) which is 20-100 pm, preferably 20-75 pm, more preferably 35-75 pm, longer than said median diameter of the core.
  • the carrier material preferably comprises a hot melt material, more preferably an oil and/or a wax, even more preferably a hydrogenated oil and/or a wax, optionally further comprising starch, preferably wherein said starch constitutes less than 15% (w/w) of said carrier material, more preferably said starch constitutes less than 10% (w/w) of said carrier material.
  • Said oil is preferably selected from the list consisting of palm oil, sunflower oil, soybean oil, rapeseed oil, coconut oil, babassu oil, palm kernel oil, maize oil, sesame oil and cottonseed oil; more preferably said oil is selected from the list consisting of palm oil, sunflower oil, soybean oil and rapeseed oil; even more preferably said oil is palm oil, most preferably said oil is hydrogenated palm oil.
  • Said wax is preferably selected from the list consisting of Candelilla wax, Carnauba wax, beeswax, rice bran wax, paraffin wax, jojoba wax, microcrystalline wax and japan wax; more preferably said wax is Candelilla wax or Carnauba wax; most preferably said wax is Candelilla wax.
  • the fucosylated MMO or all MMO's present in the encapsulate constitute 5- 50% (w/w), preferably 10-40 % (w/w), more preferably 20-40% (w/w), even more preferably 20-35% (w/w), of the total weight of the encapsulate.
  • said method reduces the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated MMO, (ii) a sialylated MMO, or (iii) a fucosylated MMO and a sialylated MMO as described herein (it is referred to the Section "Oligosaccharide").
  • FCR feed conversion ratio
  • fucosylated MMO and a sialylated MMO according to the invention are administered to said farmed animal, said fucosylated MMO and said sialylated MMO are preferably administered on the same day, more preferably administered simultaneously.
  • Simultaneous administration can be achieved by providing said fucosylated MMO and said sialylated MMO in the same composition (said composition is preferably as described in the Section "Composition"). Further, it is a preferred embodiment that the amount of said sialylated MMO administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5- 15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of all sialylated MMOs administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower than the amount of said sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 15.0, more preferably 1.5 to 15.0, even more preferably 2.5 to 15.0, even more preferably 5.0 to 15.0, even more preferably 5.0 to 12.5, most preferably 5.0 to 10.0, times lower than the amount of said sialylated MMO.
  • the amount of said fucosylated MMO administered to said animal is lower than the amount of all sialylated MMO's administered to said animal, preferably said amount of said fucosylated MMO is 1.1 to 15.0, more preferably 1.5 to 15.0, even more preferably 2.5 to 15.0, even more preferably 5.0 to 15.0, even more preferably 5.0 to 12.5, most preferably 5.0 to 10.0, times lower than the amount of all sialylated MMOs administered to said animal.
  • first sialylated MMO and a second sialylated MMO according to the invention are administered to said farmed animal
  • said first sialylated MMO and said second sialylated MMO are preferably administered on the same day, more preferably administered simultaneously.
  • the ratio between the amount of said first sialylated MMO administered to said animal and the amount of said second sialylated MMO administered to said animal is similar to this ratio as found in the mother's milk of the same species.
  • a "similar" ratio preferably refers to a ratio which is identical or falls in the range of ratio +/- 20% of said ratio, preferably ratio +/- 10% of said ratio.
  • said ratio is preferably 1.1 to 6.0, more preferably 1.1 to 5.0, even more preferably 1.25 to 4.0, even more preferably 1.25 to 3.0, even more preferably 1.5 to 3.0, most preferably 1.5 to 2.5.
  • said ratio is preferably 1.1 to 15.0, more preferably 1.1 to 12.5, even more preferably 1.1 to 10.0, even more preferably 1.5 to 10.0, even more preferably 2.5 to 10, even more preferably 5.0 to 10.0, even more preferably 7.5 to 10.0, most preferably 8.0 to 10.0.
  • said ratio is preferably 7.5-40.0, more preferably 7.5-35.0, even more preferably 10.0-35.0, even more preferably 15.0-35.0, even more preferably 20.0-35.0, most preferably 25.0-35.0.
  • said ratio is preferably 0.25-5.0, more preferably 0.25-3.0, even more preferably 0.25-2.0, even more preferably 0.25-1.5, most preferably 0.5-1.5.
  • the amount of said first sialylated MMO administered to said animal is higher than the amount of said second sialylated MMO, preferably said amount of said first sialylated MMO is 1.1 to 40.0, more preferably 1.1 to 35.0, most preferably 1.5 to 35.0, times the amount of said second sialylated MMO administered to said animal.
  • the amount of said first sialylated MMO administered to said animal is higher than the amount of said second sialylated MMO, preferably said amount of said first sialylated MMO is 1.1 to 6.0, more preferably 1.1 to 5.0, even more preferably 1.25 to 4.0, even more preferably 1.25-3.0, even more preferably 1.5 to 3.0, most preferably 1.5-2.5, times higher than the amount of said second sialylated MMO.
  • a fucosylated MMO and a first sialylated MMO according to the invention are administered to said farmed animal, said fucosylated MMO and said first sialylated MMO are preferably administered on the same day, more preferably administered simultaneously.
  • the amount of said first sialylated MMO administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower than the amount of said first sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 10.0, preferably 1.5-7.5, more preferably 2.5-7.5, most preferably 4.0-7.0, times lower than the amount of said first sialylated MMO.
  • a fucosylated MMO, a first sialylated MMO and a second sialylated MMO according to the invention are administered to said farmed animal, said fucosylated MMO, said first sialylated MMO and said second sialylated MMO are preferably administered on the same day, more preferably administered simultaneously.
  • the ratio between the amount of said first sialylated MMO administered to said animal and the amount of said second sialylated MMO administered to said animal is similar to this ratio as found in the mother's milk of the same species as described earlier herein. More preferably, the amount of said first sialylated MMO administered to said animal is higher than the amount of said second sialylated MMO, preferably said amount of said first sialylated MMO is 1.1 to 40.0, more preferably 1.1 to 35.0, most preferably 1.5 to 35.0, times higher than the amount of said second sialylated MMO.
  • the amount of said first sialylated MMO administered to said animal is higher than the amount of said second sialylated MMO, preferably said amount of said first sialylated MMO is 1.1 to 6.0, more preferably 1.1 to 5.0, even more preferably 1.25 to 4.0, even more preferably 1.25-3.0, even more preferably 1.5 to 3.0, most preferably 1.5-2.5, times higher than the amount of said second sialylated MMO.
  • the amount of said first sialylated MMO administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower than the amount of said first sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 10.0, preferably 1.5-7.5, more preferably 2.5-7.5, most preferably 4.0-7.0, times lower than the amount of said first sialylated MMO.
  • the amount of said second sialylated MMO administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower than the amount of said second sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 10.0, preferably 1.5-7.5, more preferably 1.5-5.0, most preferably 2.5-5.0, times lower than the amount of said second sialylated MMO.
  • the total amount of both first sialylated MMO and second sialylated MMO is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower than the total amount of both first sialylated MMO and second sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 15.0, preferably 1.5 to 15.0, more preferably 2.5 to 15.0, even more preferably 5.0 to 15.0, even more preferably 5.0 to 12.5, most preferably 5.0 to 10.0, times lower than the total amount of both first sialylated MMO and second sialylated MMO.
  • the amount of all sialylated MMOs that are administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated administered to said animal.
  • the amount of said fucosylated MMO administered to said animal is lower, preferably 1.1 to 15.0 times lower, more preferably 1.5 to 15.0 times lower, even more preferably 2.5 to 15.0 times lower, even more preferably 5.0 to 15.0 times lower, even more preferably 5.0 to 12.5 times lower, most preferably 5.0 to 10.0 times lower, than the amount of all sialylated MMOs administered to said animal.
  • said method according to the invention comprises administering an effective amount of said fucosylated MMO (it is referred to the Section "Oligosaccharide”) according to the invention to said farmed animal (it is referred to the Section "Subject”).
  • an "effective amount” as used throughout the application and claims is the amount of said oligosaccharide which is required to confer a reduction in the FCR of the farmed animal as described in the present application. Effective amounts vary, as recognized by those skilled in the art, depending on the subject among other known factors.
  • said fucosylated MMO is administered to said animal at least once, preferably at least twice, between birth (0 weeks) and 5 weeks of age, preferably between birth and 4 weeks of age, more preferably between birth and 3 weeks of age.
  • said fucosylated MMO is administered at a daily dose of 0.0001-15.0 g, preferably 0.0001-10.0 g, more preferably 0.0001-5.0 g, even more preferably 0.0001-2.0 g, even more preferably 0.0001-1.0 g, even more preferably 0.0005-1.0 g, most preferably 0.0010-1.0 g.
  • said fucosylated MMO is administered at a daily dose of 0.001-15.0 g, preferably 0.001-10.0 g, more preferably 0.001-5.0 g, even more preferably 0.001-2.0 g, even more preferably 0.001-1.0 g, even more preferably 0.005-1.0 g, most preferably 0.010-1.0 g. Even more preferably, said fucosylated MMO is administered at a daily dose of 0.01-15.0 g, preferably 0.01-10.0 g, more preferably 0.01-5.0 g, even more preferably 0.01-2.0 g, even more preferably 0.01-1.0 g, even more preferably 0.015-1.0 g, most preferably 0.02-1.0 g.
  • an amount of an oligosaccharide according to the invention expressed in a number of grams or milligrams per daily dose as used herein means that the amount of the oligosaccharide is such that when administering the daily dosage to a subject, the subject will be administered with the number of grams or milligrams of the oligosaccharide.
  • the daily dosage is for example 50 mg
  • the subject receives in total 50 mg per day. This may be in one or more portions. So, if the daily dosage is 50 mg divided over 2 portions, then a single serving consists of 25 mg, a daily serving consists of 2 of such single servings.
  • said fucosylated MMO is administered at a daily dose of 0.01-150.0 mg, preferably 0.01-125.0 mg, more preferably 0.01-100.0 mg, even more preferably 0.05-100.0 mg, even more preferably 0.1-100.0 mg, most preferably 0.1-80.0 mg, per kg bodyweight of said animal.
  • said fucosylated MMO is administered at a daily dose of 0.01- 1.0 g, preferably 0.01-0.75 g, more preferably 0.01-0.65 g, even more preferably 0.01-0.60 g, even more preferably 0.01-0.50 g, even more preferably 0.015-0.50 g, even more preferably 0.015-0.40 g, even more preferably 0.015-0.30 g, even more preferably 0.015-0.20 g, most preferably 0.015-0.10 g.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said fucosylated MMO is administered at a daily dose of 0.1-50.0 mg, preferably 0.1-30.0 mg, more preferably 0.1-25.0 mg, even more preferably 0.1-20.0 mg, even more preferably 0.1-15.0 mg, even more preferably 0.1-10.0 mg, even more preferably 0.25-10.0 mg, most preferably 0.5-10.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said fucosylated MMO is administered at a daily dose of 0.01-5.0 g, preferably 0.1-2.5 g, more preferably 0.1-1.5 g, even more preferably 0.1-1.2 g, even more preferably 0.2-1.2 g, even more preferably 0.3-1.2 g, even more preferably 0.4-1.2 g, most preferably 0.5- 1.2 g.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said fucosylated MMO is administered at a daily dose of 0.1-150.0 mg, preferably 0.1-125.0 mg, more preferably 1.0-125.0 mg, even more preferably 5.0-125.0 mg, even more preferably 5.0-100.0 mg, even more preferably 5.0-80.0 mg, most preferably 10.0-80.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said fucosylated MMO is administered at a daily dose of 0.0001-1.0 g, preferably 0.0001-0.50 g, more preferably 0.0001-0.10 g, even more preferably 0.0001- 0.075 g, even more preferably 0.0001-0.050 g, even more preferably 0.0002-0.050 g, even more preferably 0.0005-0.050 g, most preferably 0.0005-0.025 g.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said fucosylated MMO is administered at a daily dose of 0.1-70.0 mg, preferably 0.1-60.0 mg, more preferably 0.1-50.0 mg, even more preferably 0.5-50.0 mg, even more preferably 1.0-50.0 mg, even more preferably 2.5-50.0 mg, even more preferably 5.0-50.0 mg, even more preferably 10.0-50.0 mg, most preferably 10.0-40.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said fucosylated MMO is administered to said animal for at least
  • 1 week preferably at least 2 weeks, more preferably at least 3 weeks, even more preferably at least 4 weeks, most preferably at least 6 weeks.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal for ⁇ 32 weeks, preferably ⁇ 28 weeks, more preferably ⁇ 24 weeks, even more preferably ⁇ 20 weeks, even more preferably ⁇ 16 weeks, most preferably ⁇ 12 weeks.
  • said fucosylated MMO is administered to said animal for 1-30, preferably 2-30, more preferably 3-30, even more preferably 4-30, even more preferably 5-30, even more preferably 6-30, even more preferably 6-24, even more preferably 6-18, most preferably 6-12, consecutive weeks.
  • said fucosylated MMO is administered to said farmed animal for:
  • 1-36 preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a sheep: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a goat 1-18, preferably 1-16, more preferably 1-14, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6- 12, consecutive weeks;
  • 1-36 preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a camelid 1-14, preferably 1-12, more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a rabbit 1-12, preferably 2-12, more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a turkey 1-18, preferably 1-16, more preferably 1-14, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6- 12, consecutive weeks.
  • said fucosylated MMO according to the invention is administered at least once a week (i.e. at least one daily dosage is administered in a week), more preferably at least once every 3 days, even more preferably at least once every 2 days, most preferably at least once daily (i.e. a daily dosage is administered every day).
  • said fucosylated MMO is administered to said animal until the age of slaughtering.
  • said method according to the invention comprises administering an effective amount of said sialylated MMO (it is referred to the Section "Oligosaccharide”) according to the invention to said farmed animal (it is referred to the Section "Subject").
  • said method according to the invention comprises administering an effective amount of said first sialylated MMO (it is referred to the Section "Oligosaccharide”) according to the invention to said farmed animal (it is referred to the Section "Subject").
  • said method according to the invention comprises administering an effective amount of said first sialylated MMO and an effective amount of said second sialylated MMO (it is referred to the Section "Oligosaccharide") according to the invention to said farmed animal (it is referred to the Section "Subject").
  • sialylated MMO refers to "sialylated MMO", “first sialylated MMO” and “second sialylated MMO” as described in the application and claims (i.e. according to the invention), unless specifically stated otherwise.
  • sialylated MMO/first sialylated MMO/second sialylated MMO i.e.
  • sialylated MMO or first sialylated MMO or second sialylated MMO is indicated accordingly and each of said embodiments is hence considered to be explicitly disclosed in the context of "a sialylated MMO", “a first sialylated MMO” and “a second sialylated MMO” separately and in combination with each other, unless specifically stated otherwise.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal at least once, preferably at least twice, between birth (0 weeks) and 5 weeks of age, preferably between birth and 4 weeks of age, more preferably between birth and 3 weeks of age.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered at a daily dose of 0.0001-15.0 g, preferably 0.0001-10.0 g, more preferably 0.0001-5.0 g, even more preferably 0.0001-2.0 g, even more preferably 0.0001-1.0 g, even more preferably 0.0005-1.0 g, most preferably 0.0010-1.0 g.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered at a daily dose of 0.001-15.0 g, preferably 0.001-10.0 g, more preferably 0.001-5.0 g, even more preferably 0.001-2.0 g, even more preferably 0.001-1.0 g, even more preferably 0.005-1.0 g, most preferably 0.010-1.0 g.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered at a daily dose of 0.01-15.0 g, preferably 0.01-10.0 g, more preferably 0.01-5.0 g, even more preferably 0.01-2.0 g, even more preferably 0.01-1.0 g, even more preferably 0.015-1.0 g, most preferably 0.02-1.0 g.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered at a daily dose of 0.01-150.0 mg, preferably 0.01-125.0 mg, more preferably 0.01-100.0 mg, even more preferably 0.05-100.0 mg, even more preferably 0.1-100.0 mg, most preferably 0.1-80.0 mg, per kg bodyweight of said animal.
  • said sialylated MMO/first sialylated MMO is administered at a daily dose of 0.01-1.0 g, preferably 0.01-0.75 g, more preferably 0.025-0.75 g, even more preferably 0.05- 0.75 g, most preferably 0.05-0.50 g.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said sialylated MMO/first sialylated MMO is administered at a daily dose of 0.1-100.0 mg, preferably 0.1-75.0 mg, more preferably 0.5-75.0 mg, even more preferably 1.0-75.0 mg, even more preferably 2.5-75.0 mg, most preferably 2.5-50.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said sialylated MMO/first sialylated MMO is administered at a daily dose of 0.01-5.0 g, preferably 0.1-2.5 g, more preferably 0.1-2.0 g, even more preferably 0.1-1.5 g, even more preferably 0.2-1.5 g, even more preferably 0.3-1.5 g, even more preferably 0.4-1.5 g, most preferably 0.5-1.5 g.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said sialylated MMO/first sialylated MM is administered at a daily dose of 0.1-150.0 mg, preferably 0.5-150.0 mg, more preferably 1.0-150.0 mg, even more preferably 1.0-125.0 mg, even more preferably 2.5-125.0 mg, even more preferably 5.0- 125.0 mg, even more preferably 10.0-125.0 mg, even more preferably 25.0-125.0 mg, even more preferably 50.0-125.0 mg, most preferably 75.0-125.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said sialylated MMO/first sialylated MMO is administered at a daily dose of 0.0001-1.0 g, preferably 0.0001-0.50 g, more preferably 0.0001-0.10 g, even more preferably 0.0001-0.075 g, even more preferably 0.0001-0.050 g, even more preferably 0.0002-0.050 g, even more preferably 0.0005-0.050 g, most preferably 0.0005-0.025 g.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said sialylated MMO/first sialylated MMO is administered at a daily dose of 0.1-70.0 mg, preferably 0.1-60.0 mg, more preferably 0.1-50.0 mg, even more preferably 0.5-50.0 mg, even more preferably 1.0-50.0 mg, even more preferably 2.5-50.0 mg, even more preferably 5.0-50.0 mg, even more preferably 10.0-50.0 mg, most preferably 10.0-40.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said second sialylated MMO is administered at a daily dose of 0.01-1.0 g, preferably 0.01-0.75 g, more preferably 0.025-0.75 g, even more preferably 0.025-0.50 g, most preferably 0.025-0.25 g.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said second sialylated MMO is administered at a daily dose of 0.1-100.0 mg, preferably 0.1-75.0 mg, more preferably 0.25-75.0 mg, even more preferably 0.5-75.0 mg, even more preferably 1.0-75.0 mg, even more preferably 1.0-50.0 mg, most preferably 1.0-25.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said second sialylated MMO is administered at a daily dose of 0.01-5.0 g, preferably 0.1-2.5 g, more preferably 0.1-2.0 g, even more preferably 0.1-1.5 g, even more preferably 0.1-1.2 g, even more preferably 0.15-1.2 g, even more preferably 0.2-1.2 g, most preferably 0.25-1.2 g.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep or a goat, more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said second sialylated MMO is administered at a daily dose of 0.1-150.0 mg, preferably 1.0-150.0 mg, more preferably 1.0-125.0 mg, even more preferably 2.5-125.0 mg, even more preferably 5.0-125.0 mg, even more preferably 10.0-125.0 mg, even more preferably 25.0-125.0 mg, even more preferably 25.0-100.0 mg, most preferably 25.0-80.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said second sialylated MMO is administered at a daily dose of 0.0001-1.0 g, preferably 0.0001-0.50 g, more preferably 0.0001-0.10 g, even more preferably 0.0001-0.075 g, even more preferably 0.0001-0.050 g, even more preferably 0.0002-0.050 g, even more preferably 0.0002-0.030 g, most preferably 0.0002-0.020 g.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said second sialylated MMO is administered at a daily dose of 0.1-70.0 mg, preferably 0.1-60.0 mg, more preferably 0.1-50.0 mg, even more preferably 0.5-50.0 mg, even more preferably 1.0-50.0 mg, even more preferably 2.5-50.0 mg, even more preferably 5.0-50.0 mg, even more preferably 5.0-40.0 mg, most preferably 5.0-30.0 mg, per kg bodyweight of said animal.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal for at least 1 week, preferably at least 2 weeks, more preferably at least 3 weeks, even more preferably at least 4 weeks, most preferably at least 6 weeks.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal for ⁇ 32 weeks, preferably ⁇ 28 weeks, more preferably ⁇ 24 weeks, even more preferably ⁇ 20 weeks, even more preferably ⁇ 16 weeks, most preferably ⁇ 12 weeks.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal for 1-30, preferably 2-30, more preferably 3-30, even more preferably 4-30, even more preferably 5-30, even more preferably 6-30, even more preferably 6-24, even more preferably 6-18, most preferably 6-12, consecutive weeks.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said farmed animal for:
  • 1-36 preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a sheep: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a goat 1-18, preferably 1-16, more preferably 1-14, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6- 12, consecutive weeks;
  • 1-36 preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a camelid 1-14, preferably 1-12, more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a rabbit 1-12, preferably 2-12, more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks;
  • - if subject is a turkey 1-18, preferably 1-16, more preferably 1-14, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6- 12, consecutive weeks.
  • said sialylated MMO/first sialylated MMO/second sialylated MMO according to the invention is administered at least once a week (i.e. at least one daily dosage is administered in a week), more preferably at least once every 3 days, even more preferably at least once every 2 days, most preferably at least once daily (i.e. a daily dosage is administered every day).
  • said sialylated MMO/first sialylated MMO/second sialylated MMO is administered to said animal until the age of slaughtering.
  • a fucosylated MMO according to the invention and a sialylated MMO preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO
  • sialylated MMO is administered from the start, and preferably for at least 15.0%, more preferably for at least 20.0%, even more preferably for at least 25.0%, even more preferably for at least 40.0%, most preferably for at least 50.0% of the total period wherein the MMOs according to the invention are administered to the farmed animal (it is in this context referred to the Sections "Method to reduce FCR").
  • Said fucosylated MMO according to the invention is preferably administered to said farmed animal after at least 0%, preferably at least 10%, more preferably at least 25%, even more preferably at least 30%, most preferably at least 50%, of the total period wherein MMOs are administered to said farmed animal has passed.
  • a fucosylated MMO according to the invention and a sialylated MMO preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO
  • a fucosylated MMO according to the invention and a sialylated MMO preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO
  • FCR feed conversion ratio
  • a sialylated MMO (preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO) according to the invention primarily contributes to a decrease in FCR (likewise an increase in the average daily gain as disclosed in the third aspect of the invention) in a farmed animal from the start of the feeding regimen (i.e. the total period wherein the MMOs according to the invention are administered to the farmed animal; it is also referred to the Sections "Method to reduce FCR") until ⁇ 75.0%, preferably ⁇ 50.0% of the feeding regimen has passed.
  • a fucosylated MMO according to the inventors primarily contributes to a decrease in FCR (likewise in an increase in the average daily gain as disclosed in the third aspect of the invention) in a farmed animal not earlier than after 20.0%, preferably 25.0%, more preferably 50.0%, of the feeding regimen (i.e. the total period wherein the MMOs according to the invention are administered to the farmed animal) has passed.
  • a feeding regimen with a fucosylated MMO according to the invention and a sialylated MMO preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO
  • stage 1 administering a sialylated MMO (preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO) according to the invention and optionally administering a fucosylated MMO according to the invention, preferably administering a sialylated MMO (preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO
  • different stages refer to stages being different in the MMO's administered to the subject. If in the first stage a sialylated MMO according to the invention is administered then the second stage has to be either the administration of a fucosylated MMO according to the invention or the administration of a fucosylated MMO according to the invention and a sialylated MMO according to the invention. If in the first stage a sialylated MMO according to the invention and a fucosylated MMO according to the invention are administered to the subject, then the second stage has to be either the administration of a fucosylated MMO according to the invention or the administration of a sialylated MMO according to the invention.
  • stage 1 proceeds stage 2 and stage 1 is the start of the total period wherein the MMO(s) according to the invention are administered to the farmed animal (it is also referred to the Sections "Method to reduce FCR").
  • said stage 1 constitutes at least 15.0%, preferably at least 20.0%, more preferably at least 25.0%, even more preferably at least 30.0%, even more preferably at least 35.0%, even more preferably at least 40.0%, even more preferably at least 45.0%, most preferably at least 50.0 %, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • said stage 1 constitutes ⁇ 80.0%, preferably ⁇ 75.0%, more preferably ⁇ 70.0%, even more preferably ⁇ 65.0 %, even more preferably ⁇ 60.0%, even more preferably ⁇ 55.0 %, most preferably ⁇ 50.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 1 constitutes 15.0-80.0%, preferably 15.0-75.0%, more preferably 20.0-75.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR"). If said farmed animal is a rearing calf, than it is particularly preferred that stage 1 constitutes 35.0-75.0%, more preferably 40.0-75.0%, most preferably 50.0-75.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 1 constitutes 15.0-50.0%, more preferably 15.0-40.0%, most preferably 15.0-30.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 1 constitutes at least 2 weeks, preferably at least 3 weeks, more preferably at least 4 weeks, even more preferably at least 5 weeks, most preferably at least 6 weeks.
  • said stage 1 constitutes ⁇ 10 weeks, preferably ⁇ 9 weeks, more preferably ⁇ 8 weeks, even more preferably ⁇ 7 weeks, most preferably ⁇ 6 weeks.
  • said stage 1 constitutes 2-10 weeks, preferably 2-8 weeks, more preferably 4-8 weeks, even more preferably 4-6 weeks, most preferably 6 weeks.
  • said stage 2 constitutes at least 20.0%, preferably at least 25.0%, more preferably at least 30.0%, even more preferably at least 35.0%, even more preferably at least 40.0%, even more preferably at least 45.0%, most preferably at least 50.0 %, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • said stage 2 constitutes ⁇ 85.0%, preferably ⁇ 80.0%, more preferably ⁇ 75.0%, even more preferably ⁇ 70.0 %, even more preferably ⁇ 65.0%, even more preferably ⁇ 60.0 %, even more preferably ⁇ 55.0%, most preferably ⁇ 50.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 2 constitutes 20.0-85.0%, preferably 25.0-85.0%, more preferably 25.0- 80.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 1 constitutes 25.0-65.0%, more preferably 25.0-60.0%, most preferably 25.0-50.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 1 constitutes 50.0-85.0%, more preferably 60.0-85.0%, most preferably 70.0-85.0%, of the of the total period wherein the MMO(s) according to the invention are administered to the farmed animal as described in the present application (it is also referred to the Sections "Method to reduce FCR").
  • stage 2 constitutes at least 2 weeks, preferably at least 3 weeks, more preferably at least 4 weeks, even more preferably at least 5 weeks, most preferably at least 6 weeks.
  • said stage 1 constitutes ⁇ 22 weeks, preferably ⁇ 20 weeks. If said farmed animal is a rearing calf, than it is particularly preferred that stage 2 constitutes 2-6 weeks, preferably 2-5 weeks, more preferably 3-5 weeks, even more preferably 3-4 weeks, most preferably 3 weeks. If said farmed animal is a veal calf, than it is particularly preferred that stage 2 constitutes 6-22 weeks, preferably 8-22 weeks, more preferably 12-22 weeks, even more preferably 12- 20 weeks, most preferably 20 weeks.
  • 2'FL were administered after 50% of the total period wherein MMO('s) were administered has passed, i.e. the administration of the fucosylated MMO started after 6 weeks (and not earlier), (v) the fucosylated MMO (i.e. 2'FL) was administered to the end of the total period, i.e. administered to the end of week 12, and (vi) the fucosylated MMO (i.e. 2'FL) was administered for 50% of the total period wherein MMO('s) are administered, i.e. 6 weeks.
  • administration of 2'FL can be at least once a week, preferably at least once every 3 days, more preferably at least once every 2 days, most preferably at least once daily.
  • administration of 3'SL and 6'SL can be at least once a week, preferably at least once every 3 days, more preferably at least once every 2 days, most preferably at least once daily.
  • 3'SL and 6'SL were administered after 50% of the total period wherein MMO('s) were administered has passed, i.e. the administration of the sialylated MMO started after 6 weeks (and not earlier), (v) the sialylated MMO (i.e. 3'SL and 6'SL) were administered to the end of the total period, i.e. administered to the end of week 12, and (vi) the sialylated MMO (i.e. 3'SL and 6'SL) were administered for 50% of the total period wherein MMO('s) are administered, i.e. 6 weeks.
  • administration of 2'FL can be at least once a week, preferably at least once every 3 days, more preferably at least once every 2 days, most preferably at least once daily.
  • administration of 3'SL and 6'SL can be at least once a week, preferably at least once every 3 days, more preferably at least once every 2 days, most preferably at least once daily.
  • composition general
  • said method reduces the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated MMO, (ii) a sialylated MMO, or (iii) a fucosylated MMO and a sialylated MMO as described herein.
  • FCR feed conversion ratio
  • said fucosylated MMO (it is referred to the Section "Oligosaccharide”) is part of a composition, preferably a composition as described in the present Section "Composition”.
  • said sialylated MMO (it is referred to the Section "Oligosaccharide”) is part of a composition, preferably a composition as described in the present Section "Composition”.
  • said first sialylated MMO (it is referred to the Section "Oligosaccharide”) is part of a composition, preferably a composition as described in the present Section "Composition”.
  • said first sialylated MMO and said second sialylated MMO are part of a composition, preferably a composition as described in the present Section "Composition”.
  • each MMO according to the invention that is administered to said farmed animal in a method according to the invention are preferably part of the same composition, preferably a composition as described in the present Section "Composition”.
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide; wherein said (i), (ii) and/or (iii) are part of a composition, preferably a composition as described in the present Section "Composition" and preferably are part of the same composition.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or iii) a fucosylated mammalian milk oligosaccharide and a sialylated
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering a composition, preferably a composition as described in the present Section "Composition", to said farmed animal, wherein said composition comprises (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • Said “farmed animal” is as described in the Section "Subject”.
  • Said “method to reduce FCR” is as described in the Sections "Method to reduce FCR”.
  • Said "fucosylated MMO”, “sialylated MMO” and “fucosylated MMO and a sialylated MMO” are as described in the Section "Oligosaccharide”.
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide; wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal and wherein said (i), (ii) and/or (iii) are part of a composition, preferably a composition as described in the present Section "Composition" and preferably are part of the same composition.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosy
  • the invention provides a method to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said method comprises the step of administering a composition, preferably a composition as described in the present Section "Composition", to said farmed animal, wherein said composition comprises (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide, and wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosylated mammalian milk oligosaccharide and a sialylated mamma
  • Said “farmed animal” is as described in the Section "Subject”.
  • Said “method to reduce FCR” is as described in the Sections "Method to reduce FCR”.
  • Said "fucosylated MMO”, “sialylated MMO” and “fucosylated MMO and a sialylated MMO” are as described in the Section "Oligosaccharide”.
  • the invention provides a method of feeding a farmed animal, wherein said method comprises the step of administering to said farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide; wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal and wherein said (i), (ii) and/or (iii) are part of a composition, preferably a composition as described in the present Section "Composition" and preferably are part of the same composition.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosylated mammalian milk oli
  • the invention provides a method of feeding a farmed animal, wherein said method comprises the step of administering a composition, preferably a composition as described in the present Section "Composition", to said farmed animal, wherein said composition comprises (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide, and wherein said (i), (ii) or (iii) reduces the FCR of said farmed animal.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide
  • Said “farmed animal” is as described in the Section "Subject”.
  • Said “method to reduce FCR” is as described in the Sections "Method to reduce FCR”.
  • Said "fucosylated MMO”, “sialylated MMO” and “fucosylated MMO and a sialylated MMO” are as described in the Section "Oligosaccharide”.
  • said composition according to the invention is not mother's milk.
  • said composition according to the invention is a synthetic composition.
  • a "synthetic composition” or a “synthetic nutritional composition” refers to a composition which is artificially prepared and preferably refers to a composition comprising at least one component that is produced ex vivo, either chemically and/or biologically, e.g. by means of chemical reaction, enzymatic reaction or recombinantly, or purified by humans. It is preferred that a synthetic composition of the invention is not identical with a naturally occurring composition.
  • said fucosylated MMO and/or said sialylated MMO, preferably all MMO's according to the invention, as described herein has been isolated from a microbial cultivation or fermentation, cell culture, enzymatic reaction or chemical reaction. Or has been isolated from a natural source (it is referred to the Section "Oligosaccharide”). It is more preferred that said fucosylated MMO and/or said sialylated MMO, preferably all MMO's according to the invention, as described herein has been produced in vitro and/or ex vivo by a cell (it is referred to the Section "Oligosaccharide").
  • said composition according to the invention further comprises a microbial strain which does not use, preferably is not able to use, said fucosylated MMO and/or said sialylated MMO, preferably is not able to use any of the MMO's according to the invention, as a carbon source.
  • said composition according to the invention does not comprise a microbial strain.
  • a microbial strain is Bifidobacterium, Lactobacillus and Saccharomyces boulardii.
  • said composition according to the invention is a pharmaceutical composition, optionally further comprising a pharmaceutically acceptable carrier, filler, preservative, solubilizer, diluent, excipient, salt, adjuvant and/or solvent.
  • said composition is a nutritional composition, optionally further comprising a feed ingredient and/or a food ingredient, wherein said feed/food ingredient is preferably chosen from the list consisting of: a lipid, preferably one or more selected from the list consisting of an oil, fat, ester, monoglyceride, diglyceride, triglyceride and free fatty acid; a vitamin, preferably one or more selected from the list consisting of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E and vitamin H, or a derivate thereof; an amino acid compound; a trace element; a mineral, preferably one or more selected from the list consisting of calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, selenium and chloride; an antioxidant; a prebiotic agent, preferably one or more selected from the list consisting of GOS (galactooligosaccharide), FOS (fructo-oligosaccharide),
  • any source of protein may be used so long as it is suitable for nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition.
  • suitable proteins (and sources thereof) suitable for use in the nutritional composition according to the invention include, but are not limited to, intact, hydrolyzed, or partially hydrolyzed protein, which may be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn, wheat), vegetable (e.g., soy, pea, potato, bean), and combinations thereof.
  • milk e.g., casein, whey
  • animal e.g., meat, fish
  • cereal e.g., rice, corn, wheat
  • vegetable e.g., soy, pea, potato, bean
  • the protein may also include a mixture of amino acids (often described as free amino acids) known for use in nutritional products or a combination of such amino acids with the intact, hydrolyzed, or partially hydrolyzed proteins described herein.
  • the amino acids may be naturally occurring or synthetic amino acids.
  • suitable protein (or sources thereof) used in a nutritional composition according to the invention include, but are not limited to, whole cow's milk, partially or completely defatted milk, milk protein concentrates, milk protein isolates, nonfat dry milk, condensed skim milk, whey protein concentrates, whey protein isolates, acid caseins, sodium caseinates, calcium caseinates, potassium caseinates, legume protein, soy protein concentrates, soy protein isolates, pea protein concentrates, pea protein isolates, pea protein isolates, collagen proteins, potato proteins, rice proteins, wheat proteins, canola proteins, quinoa, insect proteins, earthworm proteins, fungal (e.g., mushroom) proteins, hydrolyzed yeast, gelatin, bovine colostrum, human colostrum, glycol macropeptides, mycoproteins, proteins expressed by microorganisms (e.g., bacteria and algae), and combinations thereof.
  • suitable protein or sources thereof used in a nutritional composition according to the invention.
  • a nutritional composition according to the invention may include any individual source of protein or combination of the various sources of protein listed above.
  • the proteins for use herein can also include, or be entirely or partially replaced by, free amino acids known for use in nutritional products, non-limiting examples of which include L-tryptophan, L-glutamine, L-tyrosine, L-methionine, L-cysteine, taurine, L- arginine, L-carnitine, and combinations thereof.
  • the carbohydrate or source of carbohydrate suitable for use in a nutritional composition according to the invention may be simple, complex, or variations or combinations thereof.
  • the carbohydrate may include any carbohydrate or carbohydrate source that is suitable for use nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition.
  • Non-limiting examples of carbohydrates suitable for use in the nutritional composition according to the invention are not limited to, polydextrose, maltodextrin; hydrolyzed or modified starch or cornstarch; glucose polymers; corn syrup; corn syrup solids; sucrose; glucose; fructose; lactose; high fructose corn syrup; honey; sugar alcohols (e.g., maltitol, erythritol, sorbitol); isomaltulose; sucromalt; pullulan; potato starch; and other slowly-digested carbohydrates; dietary fibers including, but not limited to, fructooligosaccharides (FOS), galactooligosaccharides (GOS), oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan
  • the fat or source of fat suitable for use in a nutritional composition according to the invention may be derived from various sources including, but not limited to, plants, animals, and combinations thereof.
  • the fat may include any fat or fat source that is suitable for use in a nutritional composition according to the invention and is otherwise compatible with any other selected ingredients or features in the nutritional composition.
  • Non-limiting examples of suitable fat (or sources thereof) for use in a nutritional composition according to the invention include coconut oil, fractionated coconut oil, soy oil, high oleic soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, medium chain triglyceride oil (MCT oil), high gamma linolenic (GLA) safflower oil, sunflower oil, high oleic sunflower oil, palm oil, palm kernel oil, palm olein, canola oil, high oleic canola oil, marine oils, fish oils, algal oils, borage oil, cottonseed oil, fungal oils, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), conjugated linoleic acid (CLA), alpha-linolenic acid, rice bran oil, wheat bran oil, interesterified oils, transesterified oils, structured lipids
  • the fats used in a nutritional composition for formulating infant formulas and paediatric formulas provide fatty acids needed both as an energy source and for the healthy development of the infant, toddler, or child.
  • These fats typically comprise triglycerides, although the fats may also comprise diglycerides, monoglycerides, and free fatty acids.
  • Fatty acids provided by the fats in the nutritional composition include, but are not limited to, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alphalinolenic acid, ARA, EPA, and DHA.
  • the nutritional composition can include any individual source of fat or combination of the various sources of fat listed above.
  • the fat is a mixture of vegetable fat and milk fat such as obtained from milk from a mammal like cow, sheep, goat, mare, or camel. More preferably, wherein the milk fat is bovine milk fat. Mixtures of different types of fat are preferred because they help to provide different fatty acids and better resemble the type of linkage between the glycerol moiety and the fatty acid moiety in the fat, when compared to human mother's milk.
  • the weight ratio between the oligosaccharide according to the invention and said prebiotic(s) is in the range of from 0.5:10 to 10:0.5.
  • said pharmaceutical or nutritional composition according to the invention comprises one or more probiotics for its beneficial effect on the subject's gut microbiome.
  • probiotics include Bifidobacterium, Lactobacillus and Saccharomyces boulardii.
  • said nutritional composition is a synthetic nutritional composition.
  • said nutritional composition is selected from a list consisting of a milk replacer, creep feed, prestarter diet, starter diet, pre-weaning feed, weaning feed and post-weaning feed, preferably selected form the list consisting of a milk replacer, starter diet, creep feed and post-weaning feed, more preferably said nutritional composition is a milk replacer or starter diet, most preferably a milk replacer.
  • the term "creep feed” refers to a nutritional composition which is used to supplement a pre-weaned animal with a solid diet while said animal is suckling.
  • a piglet receives creep feed to ease the transition from sow's milk to solid pig starter feed.
  • the creep feed stimulates the digestive system of the piglet to produce e.g. amylase which digests carbohydrates in dry feed. If a pig is better able to digest dry feed, he can start eating quickly post-weaning for better performance.
  • milk replacer refers to a nutritional composition which serves as a substitute for mother's milk.
  • a milk replacer comprises milk proteins, fat, carbohydrates, vitamins and minerals.
  • a milk replacer comprises 10 drywt. % to 28 drywt. % of at least one protein, 13 drywt. % to 28 drywt. % (preferably 20 drywt. % to 25 drywt. %) of at least one fat and lactose at ⁇ 55 drywt. %. More preferably, a milk replacer comprises 18 drywt. % to 24 drywt. % of at least one protein, 15 drywt. % to 28 drywt. % (preferably 20 drywt.
  • drywt. % refers to the ratio between the weight of the recited component (e.g. 2'FL) and the dry weight of the milk replacer (w/v %).
  • a milk replacer is preferably a calf milk replacer.
  • the inventors have surprisingly found that administering (i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention is sufficient to obtain an effective decrease of the FCR of a farmed animal as described herein. Administering other (oligo)saccharides is not required to obtain said FCR reduction.
  • composition can include additional (oligo)saccharides
  • the present invention relates to the fact that only (i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention is required for achieving an efficient reduction of the feed conversion ratio as described herein.
  • composition according to the invention does not comprise lacto-N-tetraose (LNT).
  • method according to the invention does not comprise the administration of lacto-N-tetraose (LNT).
  • said composition according to the invention does not comprise lacto-N-neotetraose (LNnT).
  • said method according to the invention does not comprise the administration of lacto-N-neotetraose (LNnT).
  • composition according to the invention does not comprise N-acetyllactosamine.
  • method according to the invention does not comprise the administration of N-acetyllactosamine.
  • said composition according to the invention does not comprise an oligosaccharide containing N-acetyllactosamine, preferably does not comprise a saccharide containing N-acetyllactosamine.
  • said method according to the invention does not comprise the administration of an oligosaccharide containing N- acetyllactosamine, preferably does not comprise the administration of a saccharide containing N- acetyllactosamine.
  • said composition according to the invention does not comprise a neutral non-fucosylated MMO.
  • said composition according to the invention does not comprise a fructo-oligosaccharide (FOS).
  • said method according to the invention does not comprise the administration of a fructo-oligosaccharide (FOS).
  • said composition according to the invention does not comprise a galactose-oligosaccharide (GOS). Likewise, it is a preferred embodiment that said method according to the invention does not comprise the administration of a galactose-oligosaccharide (GOS). In an additional and/or alternative preferred embodiment, said composition according to the invention does not comprise an isomaltooligosaccharide. Likewise, it is a preferred embodiment that said method according to the invention does not comprise the administration of isomaltooligosaccharide.
  • said composition according to the invention comprises only (i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention (it is referred to the Section "Oligosaccharide”).
  • said method according to the invention only comprises the administration of (i) a fucosylated MMO, (ii) a sialylated MMO or (iii) a fucosylated MMO and a sialylated MMO according to the invention (it is referred to the Section "Oligosaccharide").
  • said composition according to the invention does not comprise a neutral non-fucosylated MMO.
  • composition fucosylated MMO
  • said fucosylated mammalian milk oligosaccharide is present at 0.001- 1.000 wt. %, preferably 0.001-0.750 wt. %, more preferably 0.001-0.500 wt. %, even more preferably 0.001-0.400 wt. %, even more preferably 0.005-0.400 wt. %, even more preferably 0.005-0.300 wt. %, even more preferably 0.005-0.250 wt. %, most preferably 0.005-0.100 wt. %, of the total weight of the composition.
  • MMO fucosylated mammalian milk oligosaccharide
  • wt. % means weight by weight (i.e. w/w). If the composition is for example a solid composition, then 1.0 wt. % means 1.0 g fucosylated MMO per 100.0 gram of the solid composition. If the composition is for example a liquid composition, then 1.0 wt. % means 1.0 g fucosylated MMO per 100.0 gram of the liquid composition.
  • said fucosylated mammalian milk oligosaccharide is present at 0.001-1.000 drywt. %, preferably 0.001-0.750 drywt. %, more preferably 0.001-0.500 drywt. %, even more preferably 0.001- 0.400 drywt. %, even more preferably 0.005-0.400 drywt. %, even more preferably 0.005-0.300 drywt. %, even more preferably 0.005-0.250 drywt. %, most preferably 0.005-0.100 drywt. %.”
  • MMO fucosylated mammalian milk oligosaccharide
  • a milk replacer e.g. calf milk replacer
  • a liquid milk replacer comprises 10.0-30.0 % (VJ/V), more preferably 12.0-28.0 % (VJ/V), milk replacer powder.
  • VJ/V % VJ/V
  • the milk replacer powder is constituted in water to obtain said liquid milk replacer.
  • % VJ/V refers to the weight of the dissolved substance in gram (e.g. milk replacer powder) per 100 milliliters of the final solution (e.g. liquid milk replacer).
  • a liquid calf milk replacer comprises 10.0-20.0 % (VJ/V), more preferably 12.0-20.0 % (VJ/V), even more preferably 12.0-18.0 % (VJ/V), even more preferably 14.0-18.0 % (VJ/V), most preferably 15.0 % (VJ/V), calf milk replacer powder. It is preferred that the calf milk replacer powder is constituted in water to obtain said liquid calf milk replacer.
  • a liquid milk replacer comprises 10.0-30.0 % (VJ/V), more preferably 15.0-30.0 % (VJ/V), even more preferably 20.0-30.0 % (VJ/V), even more preferably 22.0-28.0 % (VJ/V), most preferably 25.0 % (VJ/V), milk replacer powder. It is preferred that the milk replacer powder is constituted in water to obtain said liquid calf milk replacer.
  • said fucosylated MMO is present at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.001-0.020 wt. %, even more preferably 0.001-0.010 wt. %, even more preferably 0.002-0.010 wt. %, even more preferably 0.003- 0.010 wt. %, even more preferably 0.003-0.0075 wt. %, most preferably 0.003-0.006 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said fucosylated MMO is present at 0.010-1.000 wt. %, preferably 0.010-0.750 wt. %, more preferably 0.010-0.500 wt. %, even more preferably 0.010-0.400 wt. %, even more preferably 0.050-0.400 wt. %, even more preferably 0.100-0.400 wt. %, most preferably 0.100-0.300 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said fucosylated MMO is present at 0.001-2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.025-1.000 wt. %, even more preferably 0.025-0.750 wt. %, even more preferably 0.025-0.500 wt. %, even more preferably 0.025-0.250 wt. %, even more preferably 0.025-0.100 wt. %, most preferably 0.025-0.075 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said fucosylated MMO according to the invention is provided as a powder in said composition according to the invention.
  • said powder is as defined earlier in the present Section "Oligosaccharide”. ion: MMO
  • said sialylated mammalian milk oligosaccharide (MMO) is present at 0.001- 1.000 wt. %, preferably 0.001-0.750 wt. %, more preferably 0.001-0.500 wt. %, even more preferably 0.001-0.400 wt. %, even more preferably 0.005-0.400 wt. %, even more preferably 0.005-0.300 wt. %, even more preferably 0.005-0.250 wt. %, most preferably 0.005-0.100 wt. %, of the total weight of the composition.
  • MMO sialylated mammalian milk oligosaccharide
  • said sialylated MMO is present at 0.001-0.250 wt. %, preferably 0.001- 0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.005-0.100 wt. %, even more preferably 0.005-0.075 wt. %, even more preferably 0.005-0.050 wt. %, even more preferably 0.005-0.040 wt. %, most preferably 0.010-0.040 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said sialylated MMO is present at 0.010-1.000 wt. %, preferably 0.010-0.750 wt. %, even more preferably 0.010-0.750 wt. %, even more preferably 0.010-0.500 wt. %, even more preferably 0.025-0.500 wt. %, most preferably 0.050-0.500 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said sialylated MMO is present at 0.001-2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.025-1.000 wt. %, even more preferably 0.025-0.750 wt. %, even more preferably 0.025-0.500 wt. %, even more preferably 0.025-0.500 wt. %, even more preferably 0.025-0.400 wt. %, most preferably 0.050-0.400 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said sialylated MMO according to the invention is provided as a powder in said composition according to the invention.
  • said powder is as defined earlier in the present Section "Composition”.
  • said sialylated mammalian milk oligosaccharide (MMO) is present at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.001-0.050 wt. %, even more preferably 0.005-0.050 wt. %, even more preferably 0.010- 0.050 wt. %, even more preferably 0.015-0.050 wt. %, most preferably 0.015-0.035 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said sialylated MMO is present at 0.010-1.000 wt. %, preferably 0.050-0.750 wt. %, even more preferably 0.050-0.750 wt. %, even more preferably 0.050-0.500 wt. %, most preferably 0.100-0.500 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said sialylated MMO is present at 0.001-2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.010-0.500 wt. %, even more preferably 0.015-0.500 wt. %, most preferably 0.015-0.350 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • sialylated MMO's i.e. a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's are administered
  • sialylated MMO's i.e. a first sialylated MMO and a second sialylated MMO are administered
  • said first sialylated mammalian milk oligosaccharide (MMO) is present at 0.001-1.000 wt. %, preferably 0.001-0.750 wt. %, more preferably 0.001-0.500 wt. %, even more preferably 0.001-0.400 wt. %, even more preferably 0.005-0.400 wt. %, even more preferably 0.005-0.300 wt. %, even more preferably 0.005-0.250 wt. %, most preferably 0.005-0.100 wt. %, of the total weight of the composition.
  • MMO sialylated mammalian milk oligosaccharide
  • said first sialylated MMO is present at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.001-0.050 wt. %, even more preferably 0.005-0.050 wt. %, even more preferably 0.010-0.050 wt. %, even more preferably 0.015- 0.050 wt. %, most preferably 0.015-0.035 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said first sialylated MMO is present at 0.010-1.000 wt. %, preferably 0.050-0.750 wt. %, even more preferably 0.050-0.750 wt. %, even more preferably 0.050-0.500 wt. %, most preferably 0.100-0.500 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said first sialylated MMO is present at 0.001-2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.010-0.500 wt. %, even more preferably 0.015-0.500 wt. %, most preferably 0.015-0.350 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said first sialylated MMO according to the invention is provided as a powder in said composition according to the invention.
  • said powder is as defined earlier in the present Section "Composition”.
  • said second sialylated mammalian milk oligosaccharide (MMO) is present at 0.001-1.000 wt. %, preferably 0.001-0.750 wt. %, more preferably 0.001-0.500 wt. %, even more preferably 0.001-0.400 wt. %, even more preferably 0.005-0.400 wt. %, even more preferably 0.005-0.300 wt. %, even more preferably 0.005-0.250 wt. %, most preferably 0.005-0.100 wt. %, of the total weight of the composition.
  • MMO sialylated mammalian milk oligosaccharide
  • said second sialylated MMO is present at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.001-0.075 wt. %, even more preferably 0.001-0.050 wt. %, even more preferably 0.005-0.050 wt. %, even more preferably 0.010- 0.050 wt. %, even more preferably 0.010-0.030 wt. %, most preferably 0.010-0.020 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, most preferably wherein said animal is a calf.
  • said second sialylated MMO is present at 0.010-1.000 wt. %, preferably 0.025-0.750 wt. %, even more preferably 0.050-0.750 wt. %, even more preferably 0.050- 0.500 wt. %, most preferably 0.050-0.250 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • said second sialylated MMO is present at 0.001-2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.010-0.750 wt. %, even more preferably 0.010-0.500 wt. %, even more preferably 0.010-0.300 wt. %, most preferably 0.010-0.200 wt. %, of the total weight of the composition.
  • This embodiment is for example particularly preferred if said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • said second sialylated MMO according to the invention is provided as a powder in said composition according to the invention.
  • said powder is as defined earlier in the present Section "Composition”.
  • the ratio between the amount of said first sialylated MMO in said composition and the amount of said second sialylated MMO in said composition is similar to this ratio as found in the mother's milk of the same species (as described earlier herein). More preferably, the amount of said first sialylated MMO in said composition is higher than the amount of said second sialylated MMO, more preferably said amount of said first sialylated MMO is 1.1 to 40.0, more preferably 1.1 to 35.0, most preferably 1.5 to 35.0, times higher than the amount of said second sialylated oligosaccharide in said composition.
  • the amount of said first sialylated MMO in said composition is 1.1 to 6.0, more preferably 1.1 to 5.0, even more preferably 1.25-4.0, even more preferably 1.25-3.0, even more preferably 1.5-3.0, most preferably 1.5-2.5, times higher than the amount of said second sialylated oligosaccharide in said composition.
  • a fucosylated MMO and a sialylated MMO according to the invention are administered to said farmed animal.
  • the amount of said sialylated MMO in said composition is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5- 15.0, times the amount of said fucosylated MMO in said composition.
  • the amount of said fucosylated MMO in said composition is lower than the amount of said first sialylated MMO, preferably said amount of said fucosylated MMO is 1.1 to 15.0, more preferably 1.5 to 15.0, even more preferably 2.5 to 15.0, even more preferably 5.0 to 15.0, even more preferably 5.0 to 12.5, most preferably 5.0 to 10.0, times lower than the amount of said sialylated MMO in said composition.
  • a fucosylated MMO, a first sialylated MMO and a second sialylated MMO are administered to said farmed animal.
  • the amount of said first sialylated MMO in said composition is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO in said composition.
  • the amount of said second sialylated MMO in said composition is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5- 15.0, times the amount of said fucosylated MMO in said composition.
  • the amount of said fucosylated MMO in said composition is lower than the amount of said first sialylated MMO, more preferably said amount of said fucosylated MMO is 1.1 to 10.0, preferably 1.5-7.5, more preferably 2.5-7.5, most preferably 4.0-7.0, times lower than the amount of said first sialylated MMO in said composition.
  • the amount of said fucosylated MMO in said composition is lower than the amount of said second sialylated MMO, more preferably said amount of said fucosylated MMO is 1.1 to 10.0, preferably 1.5-7.5, more preferably 1.5-5.0, most preferably 2.5-5.0, times lower than the amount of said second sialylated MMO in said composition.
  • the amount of said fucosylated MMO in said composition is lower than the amount of all sialylated MMOs in said composition, more preferably, said amount of said fucosylated MMO in said composition is 1.1 to 15.0, more preferably 1.5 to 15.0, even more preferably 2.5 to 15.0, even more preferably 5.0 to 15.0, even more preferably 5.0 to 12.5, most preferably 5.0 to 10.0, times lower than the amount of all sialylated MMOs in said composition.
  • the ratio between the amount of said first sialylated MMO in said composition and the amount of said second sialylated MMO in said composition is similar to this ratio as found in the mother's milk of the same species. More preferably, the amount of said first sialylated MMO in said composition is higher than the amount of said second sialylated MMO, more preferably said amount of said first sialylated MMO is 1.1 to 6.0, preferably 1.1 to 5.0, more preferably 1.25 to 4.0, even more preferably 1.25-3.0, even more preferably 1.5 to 3.0, most preferably 1.5-2.5, times higher than the amount of said second sialylated oligosaccharide in said composition.
  • the ratio between said fucosylated MMO and said sialylated MMO is preferably as described in the Section "Method for reducing FCR: general".
  • the ratio between said fucosylated MMO and said first sialylated MMO in said composition is preferably as described in the Section "Method for reducing FCR: general”.
  • the ratio between said fucosylated MMO and said second sialylated MMO in said composition is preferably as described in the Section "Method for reducing FCR: general".
  • the invention provides the use of (i) a fucosylated mammalian milk oligosaccharide, (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide to reduce the feed conversion ratio (FCR) of a farmed animal.
  • FCR feed conversion ratio
  • Said farmed animal is as disclosed in the Section "Subject" of the first aspect of the invention.
  • Said fucosylated MMO is as disclosed in the Sections "Oligosaccharide", “Method for reducing FCR: general” and “Method to reduce FCR: fucosylated MMO" of the first aspect of the invention.
  • Said fucosylated MMO is preferably present in a composition, it is referred to Sections "Composition: general” and 'Composition: fucosylated MMO" of the first aspect of the invention.
  • sialylated MMO is as disclosed in the Sections "Oligosaccharide", “Method for reducing FCR: general” and “Method to reduce FCR: sialylated MMO" of the first aspect of the invention.
  • Said sialylated MMO is preferably present in a composition, it is referred to Sections "Composition: general” and 'Composition: sialylated MMO" of the first aspect of the invention.
  • a particularly preferred embodiment of the second aspect of the invention is the use of a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide (preferably a first sialylated MMO and a second sialylated MMO, optionally further sialylated MMO's; more preferably a first sialylated MMO and a second sialylated MMO) to reduce the feed conversion ratio (FCR) of a farmed animal, wherein said fucosylated MMO and said sialylated MMO are administered to said farmed animal in two stages: stage 1: administering a sialylated MMO (preferably a first sialylated MMO and a second sialylated MMO).
  • the invention provides a method to increase the body weight of a farmed animal, wherein said method comprises the step of administering to said farmed animal a sialylated mammalian milk oligosaccharide (MMO) according to the invention and a fucosylated mammalian milk oligosaccharide (MMO) according to the invention, preferably wherein said sialylated MMO and said fucosylated MMO are administered to said farmed animal in a feeding regimen split in two stages as described in the first aspect of the invention.
  • said method increases the average daily gain of a farmed animal (i.e. calf fattening when said farmed animal is a calf).
  • the body weight of a farmed animal can be readily assessed by the skilled person as disclosed earlier herein.
  • the increase in body weight and increase of the average daily gain is preferably measured over a period as is disclosed for the reduction of FCR in the first aspect of the invention (it is particularly referred to the Sections "method to reduce FCR").
  • Said farmed animal is as disclosed in the Section "Subject" of the first aspect of the invention.
  • sialylated MMO is as disclosed in the Sections "Oligosaccharide", “Method for reducing FCR: general” and “Method to reduce FCR: sialylated MMO" of the first aspect of the invention.
  • Said sialylated MMO is preferably present in a composition, it is referred to Sections "Composition: general” and 'Composition: sialylated MMO" of the first aspect of the invention.
  • Said fucosylated MMO is as disclosed in the Sections "Oligosaccharide", “Method for reducing FCR: general” and “Method to reduce FCR: fucosylated MMO" of the first aspect of the invention.
  • Said fucosylated MMO is preferably present in a composition, it is referred to Sections "Composition: general” and 'Composition: fucosylated MMO" of the first aspect of the invention.
  • the method according to the invention increases the body weight (preferably average daily gain) of a farmed animal with at least 1.0 %, 2.0 %, 3.0 %, 4.0 %, 5.0 %, 6.0 %, 7.0 %, 8.0 %, 9.0 % or 10.0 %, preferably relative to said body weight (preferably average daily gain) of said animal prior to administration of said fucosylated MMO and said sialylated MMO according to the invention.
  • said body weight (preferably average daily gain) increases with at least 2.0 %, more preferably at least 2.5 %, even more preferably at least 3.0 %, even more preferably at least 3.5 %, even more preferably at least 4.0 %, even more preferably at least 4.5 %, even more preferably at least 5.0 %, most preferably at least 7.0 %.
  • the method according to the invention increases the body weight (preferably average daily gain) of a farmed animal with at least 1.0 %, 2.0 %, 3.0 %, 4.0 %, 5.0 %, 6.0 %, 7.0 %, 8.0 %, 9.0 % or 10.0 %, preferably relative to said body weight (preferably average daily gain) of said animal prior to administration of said fucosylated MMO and said sialylated MMO according to the invention.
  • the present invention preferably relates to the following specific embodiments: 1.
  • a method to reduce the feed conversion ratio (FCR) of a farmed animal comprising the step of administering to a farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO), (ii) a sialylated mammalian milk oligosaccharide, or (iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • MMO fucosylated mammalian milk oligosaccharide
  • sialylated mammalian milk oligosaccharide or iii) a fucosylated mammalian milk oligosaccharide and a sialylated mammalian milk oligosaccharide.
  • said fucosylated MMO comprises a fucose that is linked to a monosaccharide in an alpha-1,2-, alpha-1,3- or alpha-1, 4-linkage, preferably an alpha-1,2- or an alpha-1, 3-linkage, more preferably an alpha-1, 2-linkage, and wherein said monosaccharide is preferably selected from glucose, N-acetylglucosamine and galactose, more preferably said monosaccharide is glucose or galactose, even more preferably said monosaccharide is galactose.
  • said fucosylated MMO comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, preferably said fucosylated MMO comprises lactose or LacNAc at is reducing end, more preferably said fucosylated MMO comprises lactose at its reducing end.
  • a method according to any one of embodiments 1 to 9, wherein said fucosylated MMO is selected from the list consisting of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3-FL), difucosyllactose (diFL), 2'- fucosyl-N-acetyllactosamine (2'FlacNAc), difucosyl-N-acetyllactosamine (diFLacNAc), 3-fucosyl-N- acetyllactosamine (3FlacNAc), 2'-fucosyllacto-N-biose (2'FLNB), 4-fucosyllacto-N-biose (4FLNB), difucosyllacto-N-biose (diFLNB), lacto-N-fucopentaose I (LNFP I), blood group A antigen hexaose type 1 (GalNAc-LNFP I), blood group B antigen he
  • a method wherein said fucosylated MMO is administered to said animal for: if subject is bovine: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks; if subject is a pig: 1-18, preferably 1-16, more preferably 1-14, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6- 12, consecutive weeks; if subject is a sheep: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 2-12, even more preferably 3-12, even more preferably 4-12, most preferably 6-12, consecutive weeks; if subject is a goat: 1
  • % of the total weight of the composition, preferably wherein said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • a method according to embodiment 30 or 31, wherein said fucosylated MMO is present at 0.001- 2.500 wt. %, preferably 0.001-1.000 wt. %, more preferably 0.010-1.000 wt. %, even more preferably 0.025-1.000 wt.
  • sialylated MMO consists of 3- 8, preferably 3-7, more preferably 3-6, even more preferably 3-5, monosaccharides.
  • sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2,3-, alpha-2,6- or alpha-2, 8-linkage, preferably an alpha-2,3- or an alpha-2, 6-linkage, and wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine, even more preferably said monosaccharide is galactose.
  • a sialic acid preferably a Neu5Ac
  • sialylated MMO comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, lactose or LacNAc at is reducing end, most preferably said sialylated MMO comprises lactose at its reducing end.
  • LNB lacto-N-biose
  • LacNAc N-acetyllactosamine
  • sialylated MMO is selected from the list consisting of 3'-sialyllactose (3'SL), 6'-sialyllactose (6'SL), 3,6-disialyllactose, 6,6'- disialyllactose, 8,3-disialyllactose, 3'S-2'FL, 6'S-2'FL, 3'S-3-FL, 6'S-3-FL, LST a, LST b, LST c, LST d, 3'- sialyllacto-N-biose (3'SLNB), 6'-sialyllacto-N-biose (6'SLNB), sialyl Lewis a, 3'-sialyllactosamine (3'SlacNAc), 6'-sialyllactosamine (6'SlacNAc) and sialyl Lewis x; preferably said sialyl
  • sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2, 3-linkage, wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine.
  • sialylated MMO is selected from the list consisting of 3'-sialyllactose (3'SL), 3'-sialyl-2'-fucosyllactose (3'S-2'FL), 3' -sialyl-3' - fucosyllactose (3'S-3'FL), LST a, LST d, 3'-sialyl-N-acetyllactosamine (3'SlacNAc), 3'-sialyl-3- fucosyllactose and 3'-sialyllacto-N-biose (3'SLNB), preferably selected from the list consisting of 3'- sialyllactose (3'SL), LST a, LST d, 3'-sialyl-N-acetyllactosamine (3'SlacNAc) and 3'-sialyllacto-N-biose (3'SL).
  • sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2, 6-linkage, wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine.
  • sialylated MMO is selected from the list consisting of 6'-sialyllactose (6'SL), 6' -sialyl-2' -fucosyllactose (6'S-2'FL), 6'-sialyl- 3'-fucosyllactose (6'S-3'FL), Neu5Ac-a2,6-[GlcNAc-bl,3]Gal-bl,4-Glc, LST b, LST c, 6'-sialyl-N- acetyllactosamine (6'SlacNAc) and 6'-sialyllacto-N-biose (6'SLNB), preferably selected from the list consisting of 6'-sialyllactose (6'SL), LST b, LST c, 6'-sialyl-N-acetyllactosamine (6'S), preferably selected from the list consisting of 6'-sialyllact
  • sialylated MMO is linked to a carrier for delivery of said sialylated MMO, preferably wherein said carrier is a ceramide-based carrier or a polypeptide-based carrier, more preferably wherein said carrier is a ceramide-based carrier.
  • sialylated MMO is administered at a daily dose of 0.01-1.0 g, preferably 0.01-0.75 g, more preferably 0.025-0.75 g, even more preferably 0.05-0.75 g, most preferably 0.05-0.50 g, preferably wherein said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, even more preferably wherein said animal is a calf.
  • sialylated MMO is administered at a daily dose of 0.1-100.0 mg, preferably 0.1-75.0 mg, more preferably 0.5-75.0 mg, even more preferably 1.0-75.0 mg, even more preferably 2.5-75.0 mg, most preferably 2.5-50.0 mg, per kg bodyweight of said animal, preferably wherein said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, even more preferably wherein said animal is a calf.
  • sialylated MMO is administered at a daily dose of 0.1-70.0 mg, preferably 0.1-60.0 mg, more preferably 0.1-50.0 mg, even more preferably 0.5-50.0 mg, even more preferably 1.0-50.0 mg, even more preferably 2.5-50.0 mg, even more preferably 5.0-50.0 mg, even more preferably 10.0-50.0 mg, most preferably 10.0- 40.0 mg, per kg bodyweight of said animal, preferably wherein said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • % of the total weight of the composition, preferably wherein said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • % even more preferably 0.025-0.750 wt. %, even more preferably 0.025-0.500 wt. %, even more preferably 0.025-0.500 wt. %, even more preferably 0.025-0.400 wt. %, most preferably 0.050- 0.400 wt. %, of the total weight of the composition, preferably wherein said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • % more preferably 0.001-0.100 wt. %, even more preferably 0.001- 0.050 wt. %, even more preferably 0.005-0.050 wt. %, even more preferably 0.010-0.050 wt. %, even more preferably 0.015-0.050 wt. %, most preferably 0.015-0.035 wt. %, of the total weight of the composition, preferably wherein said animal is a bovine or a horse, more preferably wherein said animal is a calf or a foal, even more preferably wherein said animal is a calf.
  • % of the total weight of the composition, preferably wherein said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet.
  • composition preferably wherein said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling.
  • a method according to any one of embodiments 1 to 69, wherein said fucosylated MMO and said sialylated MMO are administered to said animal and wherein the amount of said sialylated MMO administered to said animal is 0.1-30.0, preferably 0.1-25.0, more preferably 0.1-20.0, even more preferably 0.1-15.0, even more preferably 0.2-15.0, even more preferably 0.3-15.0, even more preferably 0.4-15.0, most preferably 0.5-15.0, times the amount of said fucosylated MMO administered to said animal.
  • administering a sialylated MMO further comprises administering a second sialylated MMO.
  • a method according to embodiment 76, wherein said second sialylated MMO consists of 3-8, preferably 3-7, more preferably 3-6, even more preferably 3-5, monosaccharides.
  • a sialic acid preferably a Neu5Ac
  • LNB lacto-N-biose
  • LacNAc N-acetyllactosamine
  • said second sialylated MMO comprises a sialic acid, preferably a Neu5Ac, that is linked to a monosaccharide in an alpha-2, 6- linkage, wherein said monosaccharide is preferably selected from galactose, N-acetylglucosamine and Neu5Ac, more preferably said monosaccharide is galactose or N-acetylglucosamine.
  • a method according to any one of embodiments 76 to 101, wherein said first sialylated MMO and said second sialylated MMO are administered to said animal and wherein the amount of said first sialylated MMO administered to said animal is higher than the amount of said second sialylated MMO, preferably said amount of said first sialylated MMO is 1.1 to 40.0, more preferably 1.1 to 35.0, most preferably 1.5 to 35.0, times the amount of said second sialylated MMO administered to said animal.
  • a method according to any one of embodiments 76 to 101, wherein said first sialylated MMO and said second sialylated MMO are administered to said animal and wherein the amount of said first sialylated MMO administered to said animal is higherthan the amount of said second sialylated MMO administered to said animal, preferably said amount of said first sialylated MMO administered to said animal is 1.1 to 6.0, more preferably 1.1 to 5.0, even more preferably 1.25 to 4.0, even more preferably 1.25-3.0, even more preferably 1.5 to 3.0, most preferably 1.5-2.5, times higher than the amount of said second sialylated MMO administered to said animal.
  • % of the total weight of the composition, preferably wherein said animal is a pig, a sheep, a goat or a camelid (preferably llama or alpaca), more preferably wherein said animal is a piglet, a lamb, a kid or a cria, even more preferably wherein said animal is a piglet, a lamb or a kid, most preferably wherein said animal is a piglet. .
  • % even more preferably 0.010-0.500 wt. %, even more preferably 0.010- 0.300 wt. %, most preferably 0.010-0.200 wt. %, of the total weight of the composition, preferably wherein said animal is a fish or a crustacean, more preferably a fish, even more preferably a fry or a fingerling, even more preferably a fingerling. .
  • a method according to any one of embodiments 30-34, 62-69, 72, 73, 106-110 and 113 to 124, wherein said composition is a nutritional composition, optionally further comprising a feed ingredient, wherein said feed ingredient is preferably chosen from the list consisting of: a lipid, preferably one or more selected from the list consisting of an oil, fat, ester, monoglyceride, diglyceride, triglyceride and free fatty acid; a vitamin, preferably one or more selected from the list consisting of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E and vitamin H, or a derivate thereof; an amino acid compound; a trace element; a mineral, preferably one or more selected from the list consisting of calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, selenium and chloride; an antioxidant; a prebiotic agent, preferably one or more selected from the list consisting of GOS (galactooligo
  • a method according to embodiment 125 wherein said nutritional composition is selected from the list consisting of a milk replacer, creep feed, prestarter diet, starter diet, pre-weaning feed, weaning feed and post-weaning feed, preferably selected form the list consisting of a milk replacer, starter diet, creep feed and post-weaning feed, more preferably said nutritional composition is a milk replacer or starter diet, most preferably a milk replacer.
  • a method to reduce the feed conversion ratio (FCR) of a farmed animal comprising the step of administering to a farmed animal: (i) a fucosylated mammalian milk oligosaccharide (MMO) and a sialylated mammalian milk oligosaccharide (MMO), (ii) a fucosylated mammalian milk oligosaccharide (MMO) or (iii) a sialylated mammalian milk oligosaccharide (MMO).
  • MMO fucosylated mammalian milk oligosaccharide
  • MMO sialylated mammalian milk oligosaccharide
  • sialylated MMO comprises a sialic acid, preferably a N- acetylneuraminic acid (Neu5Ac), that is linked to a monosaccharide in an alpha-2,3- or an alpha-2, 6- linkage, and wherein said monosaccharide is galactose or N-acetylglucosamine.
  • sialic acid preferably a N- acetylneuraminic acid (Neu5Ac)
  • sialylated MMO is 3'-sialyllactose (3'SL) or 6'-sialyllactose (6'SL).
  • said fucosylated MMO and said sialylated MMO are administered to said farmed animal in two different stages: stage 1: administering said sialylated MMO and optionally administering said fucosylated MMO; and stage 2: administering said fucosylated MMO, preferably without administering said sialylated MMO.
  • sialylated MMO is a first sialylated MMO and a second sialylated MMO and optionally a further sialylated MMO.
  • said first sialylated MMO comprises a sialic acid, preferably a N-acetylneuraminic acid (Neu5Ac), that is linked to a monosaccharide in an alpha-2, 3-linkage, and wherein said monosaccharide is galactose or N- acetylglucosamine.
  • a sialic acid preferably a N-acetylneuraminic acid (Neu5Ac)
  • said second sialylated MMO comprises a sialic acid, preferably a N- acetylneuraminic acid (Neu5Ac), that is linked to a monosaccharide in an alpha-2, 6-linkage, and wherein said monosaccharide is galactose or N-acetylglucosamine.
  • a sialic acid preferably a N- acetylneuraminic acid (Neu5Ac)
  • a method to increase the body weight of a farmed animal comprising the step of administering to said farmed animal a sialylated MMO and a fucosylated MMO.
  • stage 1 administering said sialylated MMO and said fucosylated MMO
  • stage 2 administering said fucosylated MMO without administering said sialylated MMO.
  • the verbs "to comprise”, “to have” and “to contain”, and their conjugations are used in their non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded.
  • the verb "to consist essentially of” means that e.g. a composition as defined herein may comprise additional component(s) than the ones specifically identified, said additional component(s) not altering the unique characteristic of the invention.
  • the verbs "to comprise”, “to have” and “to contain”, and their conjugations may be preferably replaced by "to consist” (and its conjugations) or “to consist essentially of” (and its conjugations) and vice versa.
  • indefinite article “a” or “an” does not exclude the possibility that more than one of the element is present, unless the context clearly requires that there be one and only one of the elements.
  • the indefinite article “a” or “an” thus usually means “at least one”.
  • the word “about” or “approximately” or “around” when used in association with a numerical value preferably means that the value may be the given value (of 10) more or less 10%, preferably 5%, more preferably 1% of the value.
  • LNT II LNT-II
  • LN3 lacto-N-triose II
  • lacto-N-triose II lacto-N-triose
  • lacto-N-triose lacto-N-triose
  • GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNT lacto-N-tetraose
  • lacto-/V-tetraose lacto-/V-tetraose
  • Gal-pi,3-GlcNAc-pi,3-Gal-pi,4Glc are used interchangeably.
  • LNnT lacto-N-neotetraose
  • lacto-/V-neotetraose lacto-/V-neotetraose
  • Gaipi-4GlcNAcpi- 3Gaipi-4Glc are used interchangeably.
  • LNFP-I lacto-N-fucopentaose I
  • LNFP I lacto-N-fucopentaose I
  • LNF I OH type I determinant "LNF I”, “LNF1”, “LNF 1”, “Blood group H antigen pentaose type 1”
  • Fuc-al,2-Gal-pi,3-GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • GalNAc-LNFP-l blood group A antigen hexaose type I
  • GalNAc-al,3-(Fuc-al,2)-Gal- pi,3-GlcNAc- pi,3-Gal-pi,4-Glc are used interchangeably.
  • Gal-LNFP-I blood group B antigen hexaose type I
  • Gal-al,3-(Fuc-al,2)-Gal-pi,3- GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNFP-II lacto-N-fucopentaose II
  • Gal-pi,3-(Fuc-al,4)-GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNFP-III lacto-N-fucopentaose III
  • Gal-pi,4-(Fuc-al,3)-GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNFP-V lacto-N-fucopentaose V
  • Gal-pi,3-GlcNAc-pi,3-Gal-pi,4-(Fuc-al,3)-Glc are used interchangeably.
  • LNDFH I Lacto-N-difucohexaose I
  • LNDFH-I LNDFH I
  • LNDFH I Lacto-N-difucohexaose I
  • LNDFH-I LNDFH I
  • LNDFH I LNDFH I
  • LNDFH I LNDFH I
  • LNDFH I LNDFH I
  • LNDFH I lactose
  • Lewis-b hexasaccharide LNDFH I
  • Fuc-al,2-Gal-pi,3-[Fuc-al,4]-GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNDFH II Lacto-N-difucohexaose II
  • LDFH II Lacto-N-difucohexaose II
  • LDFH II Lacto-N-difucohexaose II
  • LDFH II Lacto-N-difucohexaose II
  • LDFH II Lacto-N-difucohexaose II
  • LDFH II LDFH II
  • Fuc-al,4-(Gal-pi,3)- GlcNAc-pi,3-Gal-pi,4-(Fuc-al,3)-Glc are used interchangeably.
  • lewis b-lewis x and "Fucal,4-[Fuc-al,2-Gaipi,3]-GlcNAc-pi,3-Gal-pi,4-[Fuc-al,3]-Glc are used interchangeably.
  • MFLNH III "monofucosyllacto-N-hexaose-lll” and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Gal- pi,3-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.
  • DFLNH (a) "difucosyllacto-N-hexaose (a)” and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,2- Gal-pi,3-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.
  • DFLNH "difucosyllacto-N-hexaose” and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,4-[Gal- pi,3]-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.
  • TFLNH "trifucosyllacto-N-hexaose” and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,4-[Fuc- al,2-Gal-pi,3]-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.
  • LNnFP I Lacto-N-neofucopentaose I
  • Fuc-al,2-Gal-pi,4-GlcNAc-pi,3-Gal-pi,4-Glc are used interchangeably.
  • LNFP-VI LNnFP V
  • lacto-N-neofucopentaose V lacto-N-neofucopentaose V
  • Gal-pi,4-GlcNAc-pi,3-Gal-pi,4-(Fuc- al,3)-Glc are used interchangeably.
  • LNnDFH Lacto-N-neoDiFucohexaose
  • Lewis x hexaose Gal-pi,4-(Fuc-al,3)-GlcNAc-pi,3- Gal-pi,4-(Fuc-al,3)-Glc
  • 2'-fucosyllacto-N-biose "2'FLNB” and "Fuc-al,2-Gal-pi,3-GlcNAc” are used interchangeably.
  • LSTa LS-Tetrasaccharide a
  • Sialyl-lacto-N-tetraose a sialyllacto-N-tetraose a
  • Neu5Ac-a2,3-Gal-bl,3-GlcNAc-bl,3-Gal-bl,4-Glc are used interchangeably.
  • LSTb LS-Tetrasaccharide b
  • Sialyl-lacto-N-tetraose b sialyllacto-N-tetraose b
  • Gal- bl,3-(Neu5Ac-a2,6)-GlcNAc-bl,3-Gal-bl,4-Glc are used interchangeably.
  • LSTc "LS-Tetrasaccharide c", "Sialyl-lacto-N-tetraose c", “sialyllacto-N-tetraose c”, “sialyllacto-N-neotetraose c" and "Neu5Ac-a2,6-Gal-bl,4-GlcNAc-bl,3-Gal-bl,4-Glc" are used interchangeably.
  • LSTd LS-Tetrasaccharide d
  • Sialyl-lacto-N-tetraose d sialyl-lacto-N-tetraose d
  • sialyllacto-N-tetraose d sialyllacto-N-neotetraose d
  • Neu5Ac-a2,3-Gal-bl,4-GlcNAc-bl,3-Gal-bl,4-Glc are used interchangeably.
  • 6'-sialyllacto-N-biose "6'SLNB” and "Neu5Ac-a2,6-Gal-bl,3-GlcNAc” are used interchangeably.
  • 6'-sialyllactosamine "6'SLacNAc” and "Neu5Ac-a2,6-Gal-bl,4-GlcNAc” are used interchangeably.
  • sialyl Lewis x , "sialyl Lex”, "5-acetylneuraminyl-(2-3)-galactosyl-(l-4)-(fucopyranosyl-(l-3))- N-acetylglucosamine” and "Neu5Ac-a2,3-Gal-pi,4-[Fuc-al,3-]GlcNAc" are used interchangeably.
  • the term “cultivation” refers to the culture medium wherein the cell is cultivated or fermented, the cell itself, and the saccharide(s) that is/are produced by the cell in whole broth, i.e. inside (intracellularly) as well as outside (extracellularly) of the cell.
  • the term "clarifying” refers to the act of treating an aqueous solution to remove suspended particulates and contaminants from the production process, like e.g. cells, cell components, insoluble metabolites and debris, that could interfere with the eventual purification of the oligosaccharide(s) of interest.
  • Such treatment can be carried out in a conventional manner by centrifugation, flocculation, flocculation with optional ultrasonic treatment, gravity filtration, microfiltration, foam separation or vacuum filtration (e.g., through a ceramic filter which can include a CeliteTM filter aid).
  • 2'-fucosyllactose (2'FL) was recombinantly produced in E. coli and purified as described in examples 10, 13 and 14 of WO 2022/034079, and subsequently spray dried as described in Example 21 of WO 2022/034079 to obtain 2"FL powder (purity 89.6 %).
  • 3'sialyllactose (3'SL) and 6'sialyllactose (6'SL) were recombinantly produced in E. coli and purified as described in WO 2022/034079 (Examples 11, 13 and 14; the E. coli strains are described in Example 3 of WO 2018/122225 for 6'SL and Example 7 of WO 2018/122225 for 3'SL wherein an alpha-2, 3- sialyltransferase from Pasteurella multocida, i.e.
  • the calf milk replacer was administered as a liquid to the calves (water was added to the CMR powder to obtain 150 gram CMR powder per liter liquid CMR).
  • Each group involved 100 calves, assigned into four rows (25 calves per row) of two compartment blocks. Each row contained five pens, where four to six calves were living in one pen.
  • calves received standard calf milk replacer (CMR) during a period of 9 weeks.
  • Group A only received the CMR, while the CMR supplied to groups B, C and D was supplemented with mammalian milk oligosaccharides as outlined in the Section "Animals”.
  • Calf starter (concentrates) and straw were introduced gradually from day 6 till the end of the experiment (12 weeks) while calves had access to corn silage at week 11 and 12. Feeds were provided ad libitum to calves twice a day in the morning and evening and were daily recorded based on rows (concentrates, straw, corn silage) or groups (CMR) consumption.
  • Stools were collected directly from recta of six calves in one selected pen upon rectal inducing at day 29 (W5) and day 57 (W9).
  • the fecal samples (approximately lg) were immediately snap frozen using isopropanol-dried ice bath for 1 min before they were transferred onto dried ice for transportation to a long-term storage at -80°C.
  • Total fecal DNA was extracted from 200 mg feces while total upper respiratory tract microbial DNA were extracted from 1 ml DNA shield reagent containing the nasal pharyngeal swab.
  • ZymoBiomicsTM DNA miniprep kit Zymo Research
  • a Fastprep® 24 device was used to extract and purify the microbial DNA as instructed by the manufacturer. Purified total DNA were eluted in 100 pl and were quickly checked for the concentration and quality using Nanodrop (Implen Nanophotometer®) before storage at -20°C.
  • Bovine reads were removed by mapping to the cow reference database Bos_taurus_UMD_3.1.1 using BMTagger (https://bioconda.github.io/recipes/bmtagger/README.html).
  • BMTagger https://bioconda.github.io/recipes/bmtagger/README.html.
  • Profiling of the taxonomic composition and the functional potential of microbial communities was done using Metaphlan (Beghini et al., 2021, Elife 10: e65088; https://huttenhower.sph.harvard.edu/humann/).
  • Microbiome data was normalized in cpm (counts per million).
  • the treatment effect of MMOs in the microbiome data was evaluated per timepoint with Maaslin2 (Mallick et al., 2021, PLoS Computational Biology 17(11): el009442) using AST transformation and adding compartment as fixed effect.
  • a score was calculated equal to -loglO(pvalue)*sign(coef). Spearman correlation was used to evaluate the relation between microbiome and FCR using the cor.test function in the stats package in R.
  • beneficial bacterial species were promoted in the microbiota of the MMO-treated calves.
  • potential pathogenic bacteria namely Atopobium deltae or Treponema succinifaciens
  • pro- inflammatory species namely Prevotella copri or Bacteroides coprophilus
  • Correlations between the abundance of the bacteria with the FCR at W6 and W12 showed negative association between beneficial bacteria and the FCR value, meaning the bacteria support feed efficiency of the calves (see Table 3).
  • the correlation between the potential pathogenic bacteria or the pro-inflammatory bacteria with the FCR value were positive, indicating worsening feed efficiency (see Table 3).
  • MMO supplementation might support gut health of the calves by promoting beneficial bacteria while inhibited potential pathogenic or pro-inflammatory bacteria so that the feed efficiency is improved.
  • the in vivo experiment was carried out at the commercial pig farm 'Degroote Luc' (Bissegem, Belgiuml).
  • the experimental design had two treatments:
  • T2 serves as control, i.e. a placebo (water) was drenched during the first 4 days of life, and subsequently a commercial milk replacer as a liquid and creep feed was offered until weaning, "T2", a 1% w/w solution of 2'FL (it is referred to Example 1) in water was drenched during the first 4 days of life, and subsequently a commercial milk replacer supplemented with 2'FL (warm water was added to 250 g of milk powder to reach 25.0 % (w/v)) and creep feed supplemented with 2'FL
  • piglets were tagged, weighed and ranked according to live weight. This was dO of the study. Then, the first drenching was given, i.e. the heaviest piglet in the pen receives Tl, the next piglet T2 and so forth, until 12 piglets of that litter were drenched. In the next litter, the order of treatment application was alternated. This practice was done in 16 litters, and drenching was repeated on dl, d2 and d3. At the d4, 128 piglets were allocated to 16 pens with 6 piglets each, in the nursery unit. Tl was applied in 8 pens, and T2 was offered in 8 remaining pens.
  • Piglets were allocated to pens according to litter of origin (from each of the 16 litters; 6 vital, normal to heavy weight piglets, body weight > 1.7 kg, were taken and half of the piglets were allocated to a pen from Tl - those receiving Tl in the first 3 days of life, and others to a pen from T2 - those receiving T2 in the first 3 days of life), and to body weight and sex. Piglets were offered the liquid milk replacer through a cup connected to a mixing-tubing system and had free access to milk at all times. Milk intake was accurately measured at pen level. From dl4 on, in addition, piglets were offered a creep feed (solid feed in feeder pan). Piglets were weighted at dO, d4, dl4 and d22 (day of weaning).
  • Total DNA were submitted to Eurofins (GATC, Germany) to perform 16S rRNA sequencing using their INVIEW microbiome high specificity package. Briefly, total DNA were first amplified the hyper-variable regions 16S and integrated the barcodes through PCR. The PCR products were purified, then ligated with adapter for library preparation. The sequencing was done using PacBio sequencing technology, guaranteed for 25000 reads, mean read length 15000 bp.
  • ADG average daily gain
  • ADFI average daily feed intake
  • SEM standard error of mean
  • DM dry matter.
  • Results - 2'FL promoted a consortium of beneficial bacteria in pig gut, which might influence feed efficiency
  • prausnitzii has been consistently reported as one of the main butyrate producers found in the intestine was promoted in piglets with a better weight gain (Cheng et al., 2019, Animal 13(3): p. 533-541). Lactobacillus mucosae has been shown to improve feed efficiency upon challenge with Lipopolysaccharide (LPS) (Li et al., 2021, J. Anim. Sci. 199(12): skab286; Chiang et al., 2015, Asian-Australas J. Anim. Sci 28(8): p. 1163-1170). Blautia are among beneficial bacteria found in pig' gut and other mammals's gut. B.
  • LPS Lipopolysaccharide
  • obeum (previously known as Ruminococcus obeum) is positively associated with feed efficiency (Bergamaschi et al., 2020, Microbiome 8(1): 110) in pigs.
  • feed efficiency Bergamaschi et al., 2020, Microbiome 8(1): 110.
  • Several studies indicate that the abundance of Prevotella spp. is inversely correlated with feed efficiency in pigs (Tan et al., 2017, Front. Microbiol. 8:1546; Quan et al., 2018, Sci. Rep. 8(1): 4536; Yang et al., 2017, Front. Microbiol. 8 :502).

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Abstract

La présente invention concerne un procédé pour réduire le taux de conversion alimentaire (FCR) d'un animal d'élevage, ledit procédé comprenant l'étape d'administration (i) d'un oligosaccharide fucosylé de lait de mammifère, (ii) d'un oligosaccharide sialylé de lait de mammifère, ou (iii) d'un oligosaccharide fucosylé de lait de mammifère et d'un oligosaccharide sialylé de lait de mammifère. L'invention concerne en outre l'utilisation (i) d'un oligosaccharide fucosylé de lait de mammifère, (ii) d'un oligosaccharide sialylé de lait de mammifère, ou (iii) d'un oligosaccharide fucosylé de lait de mammifère et d'un oligosaccharide sialylé de lait de mammifère pour réduire le FCR d'un animal d'élevage. L'invention concerne également un procédé pour augmenter le poids corporel d'un animal d'élevage, ledit procédé comprenant l'étape d'administration d'un oligosaccharide fucosylé de lait de mammifère et d'un oligosaccharide sialylé de lait de mammifère.
PCT/EP2024/062257 2023-05-04 2024-05-03 Procédé de réduction du taux de conversion alimentaire chez un animal d'élevage Pending WO2024227919A1 (fr)

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