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WO2017043963A1 - Ensemble d'éléments visant à stimuler la santé du microbiote après une naissance non naturelle - Google Patents

Ensemble d'éléments visant à stimuler la santé du microbiote après une naissance non naturelle Download PDF

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Publication number
WO2017043963A1
WO2017043963A1 PCT/NL2015/050633 NL2015050633W WO2017043963A1 WO 2017043963 A1 WO2017043963 A1 WO 2017043963A1 NL 2015050633 W NL2015050633 W NL 2015050633W WO 2017043963 A1 WO2017043963 A1 WO 2017043963A1
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Prior art keywords
infant
composition
section
kit
oligosaccharide
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Nutricia NV
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Nutricia NV
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/51—Bifidobacterium

Definitions

  • the present invention pertains to a kit of parts for improving or stimulating the healthy gut microbiota and/or reducing the risk of developing health risks and/or prevention of disorders in infants delivered via caesarean section (C-section), wherein the kit of parts comprises composition(s) to be administered to the pregnant or lactating mother of the infant and/or to the infant directly.
  • C-section caesarean section
  • EPl 940250 has clarified there is a complete lack of any detectable amounts of Bifidobacterium species in the gut of C-section infants compared to the presence of significant amounts of at least three different Bifidobacterium species of the group of B. longum, B. breve, B. infantis, B. catenulatum, B. pseudocatenulatum, B. adolescentis, B. animalis, B. gallicum, B. lactis and B. bifidum observed in infants born by natural birth.
  • Infants delivered via C-section have an intestinal microbiota which is different from the intestinal microbiota of infants born via the vaginal route. This is once more confirmed further below in Figure 1 in the experimental part.
  • infants born via C-section have a reduced rate of intestinal colonisation by Bifidobacteria and have a less diverse Bifidobacterium intestinal microbiota with regards to species than infants born via the vaginal route, particularly lacking Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum.
  • the intestinal microbiota of infants delivered via C-section have a high content of (undesirable) Enter ob acted aceae such as Klebsiella, and Escherichia coli, from birth.
  • kits of parts for improving or stimulating the health of gut microbiota and/or reducing health risks and/or prevention of disorders in infants delivered via C-section
  • the kit of parts comprises composition(s) to be administered to a pregnant woman carrying an infant to be born via C-section, to a lactating women providing human milk to an infant born via C-section and/or directly to the infant born via C-section
  • said kit of parts comprises one or more compositions(s) comprising a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp.
  • the kit of parts comprises one or more, preferably at least two, more preferably at least three of the following:
  • each composition comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • the invention also concerns a method for (a) improving or stimulating the health of gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via C-section, said method involving providing a kit of parts according to the invention and administrating each of the one or more composition(s) to a pregnant woman carrying an infant to be born via C-section, to a lactating women providing human milk to an infant born via C-section and/or to an infant born via C-section.
  • the invention also concerns the use of one or more composition(s) for the manufacture of a kit of parts for (a) improving or stimulating the health of gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via C- section, wherein each of the one or more composition(s) comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp.
  • each of the one or more composition(s) is administered to a pregnant woman carrying an infant to be born via C- section, to a lactating women providing human milk to an infant born via C-section and/or to an infant born via C-section.
  • the invention also concerns a kit of parts according to the invention for use in(a) improving or stimulating the health of gut microbiota and/or (b) reducing health risks and/or (c) prevention of disorders in infants delivered via C-section, wherein each of the one or more composition(s) is administered to a pregnant woman carrying an infant to be born via C-section, to a lactating women providing human milk to an infant born via C-section and/or to an infant born via C-section.
  • the first composition is administered to the pregnant mother when the infant is anticipated to be delivered by C-section.
  • the first composition is administered during the third trimester, more suitably during the second trimester and the third trimester, most suitably during the first trimester, second trimester and third trimester.
  • the first composition is administered at least one day prior to delivery, more suitably at least two days prior to delivery, even more suitably at least three days prior to delivery, most suitably at least one week prior to delivery.
  • the first composition may be administered before, during or after the pregnant woman is prescribed or given antibiotic therapy in anticipation of C-section delivery.
  • the first composition may suitably be administered at a time of the day different from the time of day when antibiotic therapy is administered.
  • the invention also pertains to the use of a composition for improving or stimulating the health of gut microbiota and/or reducing health risks and/or prevention of disorders in infants delivered via C-section, said composition being characterized as the first composition (i.e. composition (i)) herein.
  • the first composition is administered to the pregnant women expecting to deliver the infant by C-section.
  • the second composition is administered to the infant delivered via C-section starting at least in the first sixteen weeks after birth, preferably at least within twelve weeks after birth, even more preferably at least within eight weeks after birth, most preferably at least within four weeks after birth.
  • the second composition is administered to the infant delivered via C-section starting at least in the first two weeks after birth, preferably at least in the first week after birth, more preferably at least within 5 days after birth, even more preferably at least within 3 days after birth, most preferably at least within 2 days after birth.
  • the optional fourth composition intended for C-section infant and which may be in a different administration form and/or as a subsequent form, i.e. a form for use after the second composition.
  • the third composition is administered to the breast-feeding mother starting at least in the first sixteen weeks after birth, preferably at least within twelve weeks after birth, even more preferably at least within eight weeks after birth, most preferably at least within four weeks after birth.
  • the composition is administered to the breast-feeding mother starting at least in the first two weeks after birth, at least in the first week after birth, preferably at least within 5 days after birth, even more preferably at least within 3 days after birth, most preferably at least within 2 days after birth. It is of utmost importance to improve and/or accelerate developing the appropriate bifidobacteria population and Bifidobacterium species diversity in the gastrointestinal tract of C-section delivered infants.
  • the consequences of improving the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species according to the invention are a reduced risk of occurrence or development of allergy, preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section. Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species may also result in a reduced risk of infections, including gastrointestinal infections, and reducing the occurrence and/or severity of infections including gastrointestinal infections.
  • Figure 1 shows a comparison of the reference group and the control group in terms of total Bifidobacteria levels over the time period from day 3-5 until week 22, demonstrating that C- section infants (without any supplemented intervention directly or to the pregnant / breastfeeding mother) experience delayed colonisation of Bifidobacteria compared to vaginally delivered and breast-fed infants.
  • Figure 2 shows the same graph from Figure 1 with the addition of the results from the prebiotic group and the synbiotic group. In these results, it can be observed that levels of bifidobacteria in the synbiotic group were achieved that resemble those observed from the reference group of infants.
  • Figure 3 shows the percentage of bifidobacteria in each group relative to total bacteria at day 3-5, demonstrating that the effect of the synbiotic group generally described in Figure 2 could be observed from very early days of life.
  • a caesarean section is a surgical procedure where an infant is delivered through an incision made in the mother's abdominal wall, and then through the wall of the uterus.
  • the infant delivered via C-section may be either term or preterm human infant, where a "preterm infant” is a human infant born before 37 weeks of gestation and a "term infant” is a human born at 37 weeks or later of gestation.
  • the kit of parts according to the invention comprises one or more composition(s) to be administered to a pregnant woman carrying an infant to be born via C-section, to a lactating women providing human milk to an infant born via C-section and/or directly to the infant born via C-section, and wherein said kit of parts comprises one or more compositions(s) comprising a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infant
  • the kit of parts comprises one or more, preferably at least two, more preferably at least three of the following:
  • each composition comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • the kit of parts comprises one or more, preferably at least two, more preferably at least three of the following:
  • a fourth composition for administration to the C-section infant wherein the infant is 3 days - 6 months of age, preferably 5 days - 1 month of age, via direct administration to the infant,
  • each composition comprises a therapeutically effective amount of at least one probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • probiotic Bifidobacterium species selected from the group consisting of Bifidobacterium breve, Bifidobacterium longum subsp. longum, Bifidobacterium longum subsp. infantis and Bifidobacterium bifidum, and optionally a therapeutically effective amount of at least one non-digestible prebiotic oligosaccharide.
  • compositions comprised in the kit of parts are conveniently individually packaged, where appropriate comprising unit dose forms.
  • the optimal packaging form depends on the form taken by a specific composition.
  • the individually packaged compositions are preferably physically interconnected, such as by a single holder-packaging or single wrapper, enabling the kit to be recognised as a single unit.
  • the holder-packaging is a carton box.
  • the nutritional compositions of the kit of parts are unified by that each of the individually packaged nutritional compositions contains labelling or indicia, said labelling or indicia specifying the other nutritional compositions of the kit, or alternatively, the said labelling on the individually packed nutritional compositions making reference to the present method described hereinbelow.
  • the kit comprises (i) and at least one of (ii) and (iii). In one embodiment, the kit comprises (i), (ii) and optionally (iv). In one embodiment, the kit comprises (i) and (iii). In one embodiment, the kit comprises (i), (ii), (iii) and optionally (iv). Composition (iv) is conveniently only present in case composition (ii) is present, and is different in composition or administration form from composition (ii). In one embodiment, the kit comprises at least (ii) and (iv).
  • compositions that are comprised in the kit of parts according to the invention are:
  • a first composition being a pregnancy product (supplement for pregnant women), a second composition being a booster (e.g. small volume format) and a fourth composition being an infant formula or stick sachet for addition to human milk, infant formula or combination thereof;
  • a first composition being a pregnancy product and a second composition being stick sachet for addition to human milk, infant formula or combination thereof;
  • compositions in the present kit of parts may be the same or all compositions in the kit of parts may be different, in terms of form, dosage, volume, additional ingredients, and any other variation possible.
  • each composition is formulated in a form that is optimal for the subject to which the composition is to be administered.
  • the first composition is a composition, such as a nutritional supplement, that is especially beneficial for pregnant women, and which preferably comprises further components that are known in the art to be beneficial in this respect.
  • the second composition is a composition, such as a complete nutrition or a nutritional supplement, that is especially beneficial for newly born infants, and which preferably comprises further components that are known in the art to be beneficial in this respect.
  • the third composition is a composition, such as a nutritional supplement, that is especially beneficial for lactating women, and which preferably comprises further components that are known in the art to be beneficial in this respect.
  • the fourth composition is a composition, such as a complete nutrition or a nutritional supplement, that is especially beneficial for newly born infants, and which preferably comprises further components that are known in the art to be beneficial in this respect. Preferred forms of the compositions will be described further below. It is preferred that the fourth composition is provided in another form as the second composition.
  • the kit of parts according to the invention comprises compositions comprising a probiotic Bifidobacterium species.
  • probiotic refers to a strain of bacteria which is perceived as probiotic bringing a health benefit to the targeted infants delivered via C-section.
  • Probiotic Bifidobacteria are known in the art. It should be noted that it is preferably neither the object nor the effect of the treatment of the invention to promote colonisation by the species of probiotic that is administered but rather to promote colonisation with other bifidobacteria species so as to achieve an early bifidogenic intestinal microbiota comparable with that found in healthy, breast-fed, vaginally-delivered infants.
  • the improvement or stimulation of a healthy gut microbiota concerns the promotion of the bifidobacterial colonization of gut of C-section infants, preferably the colonization of at least one Bifidobacterium species other than the one(s) present in the composition according to the invention is promoted.
  • the compositions comprised in the kit of part according to the invention comprise B. breve and the improvement or stimulation of a healthy gut microbiota concerns the promotion of the intestinal colonization of at least one Bifidobacterium species other than B. breve.
  • compositions of the present kit of parts preferably comprise at least one Bifidobacterium selected from the group consisting of B. breve, B. longum subsp. longum, B. longum subsp. infantis, B. bifidum and B. catenulatum, even more preferably at least one Bifidobacterium selected from the group consisting of B. breve and B. longum subsp. longum, most preferably at least B. breve.
  • the composition comprises at least two different Bifidobacterium species, preferably including at least one, more preferably two of the above list, more preferably B. breve and B. longum.
  • the compositions comprise at least three, most preferably at least four different Bifidobacterium species.
  • the composition comprises a maximum of one or two Bifidobacterium species.
  • the probiotic species in the compositions of the kit consists of one or two, preferably one of the above Bifidobacterium species, and the probiotics in the compositions preferably consists of B. breve and B. longum subsp. longum, most preferably consists of B. breve.
  • compositions of the present kit of parts further comprise a Lactobacillus selected from the group consisting of L. casei, L. reuteri, L paracasei, L. rhamnosus, L. acidophilus, L. johnsonii, L. lactis, L. salivarius, L. crispatus, L. gasseri, L. zeae, L. fermentum and L. plantarum, more preferably L. casei, L. paracasei, L. rhamnosus, L. johnsonii, L. acidophilus, L. fermentum and most preferably L. paracasei.
  • a Lactobacillus selected from the group consisting of L. casei, L. reuteri, L paracasei, L. rhamnosus, L. acidophilus, L. johnsonii, L. lactis, L. salivarius, L. crispatus, L. gasseri, L. zeae, L. fermentum and L. plantarum, more
  • the probiotic(s) is(are) present in the compositions of the kit of parts in a therapeutically effective amount or "amount effective for treating" in the context of the invention.
  • the optimal content of probiotics aill vary depending on the form of the composition and the target group, but in general terms it is preferred that the probiotic is included in an amount of
  • compositions according to the invention are in the form of a supplement to be added to a nutritional product or to be ingested as such, the content of the probiotics therein may be somewhat higher, such as 10 4 to 10 16 cfu/g, suitably 10 7 to 10 13 cfu/g, more suitably 10 10 to 10 12 cfu/g, based on dry weight of the supplement.
  • Non-digestible prebiotic oligosaccharides may be somewhat higher, such as 10 4 to 10 16 cfu/g, suitably 10 7 to 10 13 cfu/g, more suitably 10 10 to 10 12 cfu/g, based on dry weight of the supplement.
  • compositions of the present kit of parts comprises at least one non-digestible prebiotic oligosaccharide.
  • oligosaccharide refers to saccharides with an average degree of polymerization (DP) of 2 to 250, preferably an average DP 2 to 100, more preferably 2 to 60.
  • the term "prebiotic” refers to one or more non- digestible oligosaccharides.
  • the non-digestible oligosaccharide is water- soluble (according to the method disclosed in L. Prosky et al, J. Assoc. Anal. Chem. 71 : 1017- 1023, 1988).
  • Non-digestible oligosaccharides are not digested in the intestine by the action of digestive enzymes present in the upper digestive tract (small intestine and stomach) of the C- section infant but instead are fermented by the intestinal microbiota of said infant, thus conferring benefits upon the host wellbeing and health.
  • the growth of at least bifidobacteria and preferably also Lactobacilli is stimulated.
  • An increased content of bifidobacteria and/or lactobacilli stimulate the formation of a healthy intestinal microbiota..
  • Suitable non-digestible oligosaccharides are selected from the group consisting of fructo- oligosaccharide, non-digestible dextrin, galacto-oligosaccharide, xylo-oligosaccharide, arabino-oligosaccharide, arabinogalactooligosaccharide, gluco-oligosaccharide, glucomannooligosaccharide, galactomanno-oligosaccharide, mannanoligosaccharide, chito- oligosaccharide, uronic acid oligosaccharide, sialyl-oligosaccharide and fuco-oligosaccharide.
  • the non-digestible oligosaccharides comprise those obtainable from human milk.
  • the present non-digestible oligosaccharide is preferably selected from the group consisting of galacto-oligosaccharides and fructo-oligosaccharides (including fructo-polysaccharides such as inulin). Preferably at least 50 wt.% of the present non-digestible oligosaccharides have an average degree of polymerisation of 2 to 60.
  • the non-digestible oligosaccharide comprises galacto-oligosaccharides, in particular ⁇ -galacto-oligosaccharides.
  • the galacto-oligosaccharides are preferably [galactose] n -glucose; wherein n is an integer between 1 and 60, i.e.
  • n 2, 3,4,5, 6,...., 59, 60; preferably n is 2, 3, 4, 5, 6, 7, 8, 9 and/or 10, a good example being tram'-galacto-oligosaccharides.
  • the galacto-oligosaccharides preferably comprise saccharides with an average DP of 2 to 10 (scGOS).
  • (Trans)galactooligosaccharide is for example available under the trade name Vivinal®GOS (Borculo Domo Ingredients, Zwolle, Netherlands), Bimuno (Clasado), Cup-oligo (Nissin Sugar) and 01igomate55 (Yakult).
  • Fructo-oligosaccharides may be inulin hydrolysate products having an average DP within the aforementioned (sub-)ranges.
  • Such fructo-oligosaccharide products are for instance short-chain fructooligosacharides (scFOS) commercially available such as the product sold under the trade mark Beneo® P95 or Raftilose P95 (Orafti).
  • scFOS short-chain fructooligosacharides
  • Beneo® P95 or Raftilose P95 (Orafti) A particular type of long-chain fructo-oligosaccharide (lcFOS) is inulin, such as Raftilin FIP.
  • compositions of the present kit of parts comprise at least galacto-oligosaccharides and fructo-oligosaccharides oligosaccharides and/or fructopolysaccharides, preferably scGOS and lcFOS (preferably having an average DP > 15), suitably in a weight ratio 5: 1 - 20: 1, even more suitably 7: 1 - 15: 1, even more suitably 8: 1 - 10 : 1 , most suitably about 9: 1.
  • compositions of the present kit of parts suitably comprise 0.05 to 20 wt% of said non-digestible oligosaccharides, more suitably 0.5 to 15 wt%, even more suitably 1 to 10 wt%, most suitably 2 to 10 wt%, based on dry weight of the compositions of the kit.
  • compositions of the present kit of parts may further comprise long chain polyunsaturated fatty acids (LC-PUFA).
  • LC-PUFA are fatty acids wherein the acyl chain has a length of 20 to 24 carbon atoms (preferably 20 or 22 carbon atoms) and wherein the acyl chain comprises at least two unsaturated bonds between said carbon atoms in the acyl chain.
  • the present compositions comprises at least one LC-PUFA selected from the group consisting of eicosapentaenoic acid (EPA, 20:5 n3), docosahexaenoic acid (DHA, 22:6 n3), arachidonic acid (ARA, 20:4 n6) and docosapentaenoic acid (DP A, 22:5 n3), comprising at least DHA.
  • LC-PUFA further have anti-inflammatory effects and promote the adhesion of lactic acid producing bacteria to mucosal surfaces, thereby stimulating the development of a healthy microbiota, which are further advantages for use in C-section delivered infants.
  • the LC- PUFA may be provided as free fatty acids, in triglyceride form, in diglyceride form, in monoglyceride form, in phospholipid form, or as a mixture of one of more of the above.
  • the present compositions preferably comprises at least one of ARA and DHA in phospholipid form.
  • compositions in the present kit of parts are enterally administered, and the term "enteral” is intended to refer to the delivery directly into the gastrointestinal tract of the infant (e.g., orally or via a tube, catheter or stoma), but it also encompasses rectal or anal administration.
  • enterally is intended to refer to the delivery directly into the gastrointestinal tract of the infant (e.g., orally or via a tube, catheter or stoma), but it also encompasses rectal or anal administration.
  • the compositions are intended for oral administration.
  • compositions in the present kit of parts may be in any form known in the art, such as in solid form, in semi-solid form or in liquid form.
  • the compositions are a nutritional composition or a nutritional supplement, preferably in the form of a powder, capsule or tablet.
  • the compositions comprise the probiotic in freeze-dried form, which is especially suitable when the compositions are in powder, capsule or tablet form.
  • the compositions, when in powder, capsule or tablet form, especially when in powder form are contained within a container, preferably a stick or stickpack or a sachet.
  • the second or fourth composition to be administered to the C-section infant may be in the form of complete nutrition.
  • the second or fourth composition may comprise an infant formula, preferably in powder form suited to be reconstituted with water.
  • the second or fourth composition is an infant formula.
  • An infant formula for use according to the present invention may contain a protein source in an amount of not more than 2.0 g/lOOkcal, preferably 1.8 to 2.0 g/lOOkcal.
  • the protein preferably provides 5 to 15% of the total calories.
  • the composition comprises protein that provides 6 to 12% of the total calories. More preferably protein is present in the infant formula below 9% based on calories.
  • the source of the protein should be selected in such a way that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured.
  • the infant formula comprises casein and whey protein.
  • the protein source is preferably based on acid whey or sweet whey, whey protein isolate or mixtures thereof and may include alpha-lactalbumin and alpha-lactoglobulin. More preferably, the protein source is based on acid whey or sweet whey from which caseino- glyco-macropeptide (CGMP) has been removed.
  • the infant formula comprises casein, preferably it comprises at least 3 wt.% casein based on dry weight.
  • the casein is intact and/or non-hydrolyzed.
  • protein includes peptides and free amino acids.
  • the protein source may be based on acid whey or sweet whey or mixtures thereof and may include alpha-lactalbumin and beta- lactoglobulin in whatever proportions are desired.
  • the proteins may be intact or hydrolysed or a mixture of intact and hydrolysed proteins.
  • the infant formula may contain a carbohydrate source. Any carbohydrate source conventionally found in infant formulae such as lactose, saccharose, maltodextrin, starch and mixtures thereof may be used although the preferred source of carbohydrates is lactose.
  • the carbohydrate sources contribute between 35 and 65% of the total energy of the formula.
  • the infant formula may also contain a source of lipids.
  • the lipid source may be any lipid or fat which is suitable for use in infant formulas.
  • the infant formula contains at least one, suitably at least two lipid sources selected from the group consisting of rape seed oil (such as colza oil, low erucic acid rape seed oil and canola oil), high oleic sunflower oil, high oleic safflower oil, olive oil, marine oils, microbial oils, coconut oil, palm kernel oil and milk fat.
  • the lipid component of the infant formula suitably provides 2.9 to 6.0 g, more suitably 4 to 6 g per 100 kcal of the composition.
  • the infant formula When in liquid form, the infant formula suitably comprises 2.1 to 6.5 g lipid per 100 ml, more suitably 3.0 to 4.0 g per 100 ml. Based on dry weight the infant formula suitably comprises 12.5 to 40 wt% lipid, more suitably 19 to 30 wt%.
  • the fat source preferably has a ratio of n-6 to n-3 fatty acids of about 5: 1 to about 15: 1; for example about 8: 1 to about 10: 1.
  • the infant formula may also contain all vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts. Minimum requirements have been established for certain vitamins and minerals.
  • Examples of minerals, vitamins and other nutrients optionally present in the infant formula include vitamin A, vitamin Bl, vitamin B2, vitamin B6, vitamin B 12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form.
  • the infant formula may optionally contain other substances which may have a beneficial effect such as lactoferrin, nucleotides, nucleosides, and the like.
  • the second or fourth compositions of the kit of parts of the invention are not in the form of complete nutrition.
  • the second compositions may be intended to be administered to the infant directly and in addition to breast-milk or infant formula ingested by the infant.
  • Such compositions are typically of small size, e.g. 0.5 - 5 ml or 0.5 - 5 g, and may be referred to as supplement or fortifier.
  • the invention thus pertains to a method for the manufacture of a nutritional product for infants born via caesarean section comprising admixing: (a) human breast milk, infant formula or a mixture thereof; and (b) the second composition according to the invention.
  • the invention concerns a method for providing nutrition to an infant, said method comprising the admixing of (a) and (b) to manufacture a nutritional product as defined above and administering the nutritional product thus obtained to an infant born via caesarean section, preferably in the aforementioned short time frames after birth.
  • compositions may also be administered to the infant with a syringe, pipette or tube, thus especially useful for C-section infants in hospital settings.
  • the composition is preferably administered in liquid form having a volume between 0.5 to 5 ml.
  • the compositions may be provided in the form of unit dose form, which refers to individual single-use packages.
  • the composition may be present in a container containing one single or more unit dose(s).
  • the second composition is intended to be added to another product before ingestion by the infant.
  • the present composition is accompanied with instructions to add the composition to a nutritional product before ingestion.
  • the nutritional product to which the present composition is to be added may be any suitable nutritional product fro C-section infants, such as breast-milk or infant formula.
  • composition of the present kit of parts is rectally or anally administered to the mother and/or infant, preferably in the form of a suppository, pill or tablet.
  • a suppository, pill or tablet Any base components commonly used for suppositories can be used as a base component of the suppository of the present invention, including oils and fats, waxes, and the like of animal, vegetable or mineral origins. They may be partially or totally synthesised materials.
  • the kit of parts of the present invention is for improving or stimulating the healthy gut microbiota and/or reducing the risk of developing health risks and/or prevention of disorders in infants delivered via C-section.
  • the invention pertains to a method for
  • kits of parts according to the invention comprising at least two, preferably at least three of the following:
  • the embodiments (b) and (c) involve risks and disorders associated with the impaired gut microbiota balance, particularly the lack of bifidobacteria microbiota, of C-section delivery infants at the onset of life.
  • the treatment is targeted at the infant delivered via C-section at least in the first two weeks after birth, preferably within the first week after birth, more preferably at least within 5 days after birth, even more preferably at least within 3 days after birth, most preferably at least within 2 days after birth. It shows from Figures 2 and 3 that the impact is most dramatic in the early onset.
  • Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species results in a reduced risk of occurrence of allergy, preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section.
  • allergy preferably food allergy, eczema (e.g. atopic dermatitis), asthma, allergic rhinitis and/or allergic conjunctivitis in infants delivered by C-section.
  • Improvement of the gastrointestinal Bifidobacterium population in terms of numbers and diversity of species may also result in a reduced risk of infections, including gastrointestinal infections, and including reducing the occurrence and/or severity of infections, such as infections due to reduction of intestinal concentrations of pathogens particularly Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus haemolyticus, Streptococcus, Clostridium difficile, Bacilus subtilis, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, Proteus, Aeromonas and Escherichia coli.
  • pathogens particularly Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus haemolyticus, Streptococcus, Clostridium difficile, Bacilus subtilis, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acineto
  • C-section has also been associated with increased risks of developing allergies and obesity later in life, and the improvements in terms of swift microbiota restoration achieved by the invention thus also relate to reducing the risks of developing allergies and obesity later in life, meaning at an age exceeding the age at which the infant receives the composition, suitably exceeding the age by at least 12 months, more suitably by 24 months, by 36 months, by 5 years, most suitably by 8 years.
  • "later in life” means at toddler age, childhood age, adolescence age, or adult age.
  • 'scGOS' are short- chain galactooligosaccharides (Vivinal-GOSTM; Borculo Domo Ingredients, Netherlands; Degree of Polymerisation [DP] 2 - 8), 'lcFOS' are long-chain fructooligosaccharides (Raftiline HPTM, Orafti, Tienen, Belgium; average DP 22 - 25).
  • Figure 1 shows a comparison of the reference group and the control group in terms of total Bifidobacteria levels over the time period from day 3-5 until week 22, demonstrating that C- section infants (without any supplemented intervention directly or to the pregnant / breastfeeding mother) experience delayed colonisation of bifidobacteria compared to vaginally delivered and breast-fed infants.
  • Figure 2 shows the same graph from Figure 1 with the addition of the results from the prebiotic group and the synbiotic group. In these results, it can be observed that levels of bifidobacteria in the synbiotic group were achieved that resemble those observed from the reference group of infants.
  • Figure 3 shows the percentage of bifidobacteria in each group relative to total bacteria at Day 3-5, demonstrating that the effect of the synbiotic group generally described in Figure 2 could be observed from very early days of life.
  • kits are accompanied from instructions directed to the treatment of C-section delivery infants.
  • Kit 1 comprises:
  • a first composition being a pregnancy product (supplement for pregnant women);
  • a second composition being a booster (volume of 5 ml) for C-section delivery infant
  • a fourth composition being an infant formula
  • Kit 2 comprises:
  • a first composition being a pregnancy product (supplement for pregnant women);
  • a second composition being a booster (volume of 5 ml) for C-section delivery infant
  • a fourth composition being a stick sachet for addition to human milk, infant formula or combination thereof.
  • Kit 3 comprises:
  • a first composition being a pregnancy product (supplement for pregnant women);
  • Kit 4 comprises:
  • a first composition being a pregnancy product (supplement for pregnant women); and (ii) a second composition being stick sachet for addition to human milk, infant formula or combination thereof.
  • Kit 5 comprises:
  • a first composition being a pregnancy product (supplement for pregnant women); and (iii) a third composition being a lactation product (supplement for lactating women).
  • compositions in these exemplary kits of part comprise B. breve and a mixture of galaco- oligosaccharides and fructo-oligosaccharides.

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  • Health & Medical Sciences (AREA)
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  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention se rapporte à un ensemble d'éléments comprenant une ou plusieurs compositions destinées à être administrées à (i) une femme enceinte portant un bébé devant naître par césarienne, (ii) une femme allaitante nourrissant de lait humain un nourrisson né par césarienne et/ou (iii) un nourrisson né par césarienne, et dans lequel chacune de ladite ou desdites compositions comprend une quantité thérapeutiquement efficace d'au moins un probiotique du genre Bifidobacterium, choisi dans le groupe constitué de Bifidobacterium breve, Bifidobacterium longum, sous-espèce longum, Bifidobacterium longum, sous-espèce infantis et Bifidobacterium bifidum.
PCT/NL2015/050633 2015-09-11 2015-09-11 Ensemble d'éléments visant à stimuler la santé du microbiote après une naissance non naturelle Ceased WO2017043963A1 (fr)

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WO2019002612A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles métaboliques
WO2019002609A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles métaboliques
WO2019002607A1 (fr) * 2017-06-30 2019-01-03 N.V. Nutricia Composition symbiotique pour la prévention de troubles
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CN114276961A (zh) * 2021-12-30 2022-04-05 光明乳业股份有限公司 一种长双歧杆菌婴儿亚种ccfm1192菌株、发酵剂及其制备方法与应用

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