WO2025207472A1 - Pet food compositions - Google Patents

Abstract

Disclosed herein are methods of treating, preventing, or alleviating periodontal disease of a companion animal, the method comprising administering to a companion animal in need thereof a composition comprising an effective amount of D-ribose. Also disclosed herein are compositions comprising D-ribose and methods of making the same.

Description

PET FOOD COMPOSITIONS

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority from U.S. Provisional Patent Application No. 63/569,996, filed 26 March 2024, the contents of which are hereby incorporated herein by reference in their entirety.

BACKGROUND

[0002] Many animals, including domestic companion animals, e.g., canine and feline companion animals, accumulate dental plaque and calculus (tartar). These accumulations can lead to the animal's affliction with periodontal disease. Many pets suffer from gingivitis, which, in turn, can progress to periodontitis that may eventually lead to even more serious systemic diseases and conditions. Animals afflicted with these dental conditions can also be generally afflicted with halitosis and stomatitis. It is estimated that over 70% of dogs have some degree of gingival or periodontal disease.

[0003] Dental plaque is formed as a result of the bacterial colonization of teeth and comprises a layer of bacteria on the erupted surfaces of teeth and in the gingival crevice. More specifically, dental plaque is a biofilm, usually a pale yellow film that develops naturally on the teeth. Like any biofilm, dental plaque is formed by colonizing bacteria that attach themselves to a smooth surface, such as the surface of a tooth. Plaque comprising specific bacterial species can lead to the development of dental caries and periodontal disease.

[0004] Dental calculus, or tartar, is a recurring calcified deposit on the surfaces of the teeth of many animals, including humans, primates, and domesticated dogs and cats. It is generally recognized that dental calculus develops in a sequential process that involves the accumulation of dental plaque and the subsequent calcification of the plaque by saliva, which contains high concentrations of calcium and phosphate. Thus, dental calculus or tartar is a form of hardened dental plaque resulting from the continual accumulation of minerals from saliva on plaque that has developed on the teeth. The rough surface of calculus provides an ideal medium for further plaque formation, in somewhat autocatalytic manner that, if uninterrupted, can threaten gingival health.

[0005] Brushing and flossing can remove the plaque from which tartar forms. Once tartar has been formed, however, it is generally too hard and firmly attached to be removed with a toothbrush. The accumulation of plaque and its sequential solidification or calcification as dental calculus or tartar eventually causes the gingiva to become irritated and inflamed, i.e., the condition referred to as gingivitis. Gingivitis in turn can progress and develop into periodontitis, which is characterized by a loss of the connective tissue fibers that attach the gums to the teeth and bone that surrounds the tooth. Calculus (tartar) is detrimental to gingival health because it serves as a substrate for increased plaque formation and retention.

[0006] Because dental plaque is a combination of bacteria, bacterial by-products that form a glycoprotein matrix, and salivary precipitates that bind to the tooth surface, and because the microorganisms making up dental plaque are recognized as the etiological agents responsible for the development of tartai' and the subsequent inflammation of the oral soft tissues, it is well accepted that measures that inhibit the growth of such microorganisms will inhibit the progression to calculus accumulation, gingivitis, and ultimately to periodontitis.

[0007] Pets are more susceptible to the formation of plaque and calculus than animals in the wild. This is due to the nature of the foods that pets eat. In the wild, many animals eat foods that mechanically abrade plaque and calculus from the teeth. In contrast, pets are usually fed pet foods that generally provide better nutritional value, but do not in general subject the teeth to abrasive forces sufficient to clean the teeth.

[0008] Maintenance of optimal dental health for pets depends on regular professional cleaning of the accumulations both above and below the gum line, as well as adequate home care. Mechanical cleansing of the tooth surfaces through tooth brushing or pet food compositions that when chewed by pets, cause a mechanical, abrasive cleaning of the pets’ teeth are effective means of controlling the buildup of plaque and calculus in both humans and pets. However, most pet owners are reluctant or unable to provide the routine brushing necessary to maintain good oral health in their pets.

[0009] Thus, a need exists for food products, compositions, solutions or methods that are useful for the effective control, reduction, or inhibition of formation of dental plaque and calculus in animals.

BRIEF SUMMARY

[0010] This summary is intended merely to introduce a simplified summary of some aspects of one or more implementations of the present disclosure. Further areas of applicability of the present disclosure will become apparent from the detailed description provided hereinafter. This summary is not an extensive overview, nor is it intended to identify key or critical elements of the present teachings, nor to delineate the scope of the disclosure. Rather, its purpose is merely to present one or more concepts in simplified form as a prelude to the detailed description below.

[0011] Aspects of the disclosure are directed to pet food compositions and methods of use thereof for reducing plaque and tartar accumulation and/or improving the oral health of pets. In accordance with one aspect, provided is a composition, such as a pet food composition, comprising D-ribose. [0012] According to certain aspects, provided is a method of treating, preventing, or alleviating periodontal disease of a companion animal, the method comprising administering to a companion animal in need thereof a composition (e.g., a pet food composition) comprising an effective amount of D-ribose. In certain embodiments, the D-ribose is present in the composition in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the composition. The method may include providing and/or feeding the canine a composition disclosed herein. In some instances, the method may include providing and/or feeding the canine the compositions for 1 or more days, preferably 5 or more days, preferably 7 or more days, preferably 10 or more days, preferably 14 or more days, preferably 30 or more days, or preferably 42 or more days.

[0013] According to certain embodiments, the periodontal disease of the companion animal is treated or alleviated by reducing the amount of at least one of tartar or plaque on the teeth of the companion animal as compared to before the composition was administered to the companion animal, and in certain embodiments, the methods disclosed herein reduce at least one of Fusobacterium nucleatum or Porphyromonas gingivalis present on the teeth of the companion animal as compared to before the composition was administered to the companion animal.

[0014] In various embodiments, the composition is a pet food composition and is in a form selected from a dry kibble, a wet loaf, dental chew, or a treat, preferably a dry kibble, and in certain embodiments, the D-ribose is in a coating enrobing the dry kibble. In various embodiments, the composition is in the form of a dentifrice, such as a paste, gel, mouthwash, dental rinse, or tablet, for oral care, e.g., a toothpaste composition.

[0015] According to certain embodiments, the pet food composition further comprises at least one mechanical component for cleaning teeth, e.g., a transverse, fibrous striated matrix.

[0016] Also disclosed herein is a composition (e.g., a pet food composition) for treating, preventing, or alleviating periodontal disease of a companion animal, the composition comprising an effective amount of D-ribose. Optionally, the composition is a pet food composition and is in the form of a kibble comprising a coating comprising the D-ribose, or alternatively the composition is a dentifrice and is in the form of a paste, gel, or tablet (c.g., a toothpaste composition). In certain embodiments, the composition is free of any additional sugars. In certain embodiments, the composition is a pet food composition comprising a coating, and the coating further comprises at least one palatant.

[0017] Further disclosed herein is a method for reducing the accumulation of tartar comprising administering to a companion animal a composition as disclosed herein. In another embodiment, disclosed herein is method for reducing the accumulation of plaque comprising administering to a companion animal a composition as disclosed herein. In yet another embodiment, there is provided a method for reducing an amount of Fusobacterium nucleatum and/or Porphyromonas gingivalis in an oral cavity comprising administering to a companion animal a composition as disclosed herein.

[0018] In accordance with a further aspect, disclosed herein is a method of making a pet food composition for treating, preventing, or alleviating the symptoms of periodontal disease, the method comprising: (a) mixing wet and dry ingredients to form a dough; (b) extruding the dough to form an extruded kibble; (c) drying the extruded kibble; and (d) enrobing the dried kibble with a topical liquid and/or dry ingredients, wherein D-ribose is applied to the kibble at step (a) and/or step (d), in an amount effective to treat, prevent, or alleviate the symptoms of periodontal disease in a companion animal who consumes the pet food composition. In certain embodiments, the D- ribose is added to the kibble at step (a), when mixing wet and dry ingredients to form a dough, and in certain embodiments, the D-ribose is added to added to the kibble at step (d), in the form of a topical liquid or dry ingredient, when enrobing the dried kibble with the topical liquid and/or dry ingredients. In certain embodiments of the methods of making a pet food composition disclosed herein, the D-ribose is applied in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the pet food composition.

[0019] According to certain embodiments of any aspect of the disclosure, the companion animal is a cat or a dog, preferably a dog. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] The features and advantages of the disclosure will be apparent from the following more detailed description of certain embodiments of the disclosure and as illustrated in the accompanying drawings in which:

[0021] FIG. 1 is schematic drawing illustrating the experimental design of the food study as described in Example 1 herein, wherein “A” represents the positive control food, “B” represents the Test Food 1, “C” represents the negative control food, and “D” represents the Test Food 2.

[0022] FIG. 2 is a bar graph of whole mouth plaque scores of dogs fed the negative control food, the positive control food, Test Food 1, and Test Food 2, wherein the letters over the bars represent significantly different (p < 0.05) results by mixed model analyses followed by Tukey post-hoc test, as described in Example 1.

[0023] FIG. 3 is a bar graph of Fusobacterium nucleatum abundance levels in the sub-gingival plaque samples of healthy teeth and unhealthy teeth (left), as well as in the sub-gingival plaque samples of dogs fed the negative control food, the positive control food, Test Food 1, and Test Food 2 (right), wherein the letters over the bars represent significantly different (p < 0.05) results by mixed model analyses followed by Tukey post-hoc test, as described in Example 1.

[0024] FIG. 4 is a bar graph of Porphyromonas gingivalis abundance levels in the sub-gingival plaque samples of healthy teeth and unhealthy teeth (left), as well as in the sub-gingival plaque samples of dogs fed the negative control food, the positive control food, Test Food 1, and Test Food 2 (right), wherein the letters over the bars represent significantly different (p < 0.05) results by mixed model analyses followed by Tukey post-hoc test, as described in Example 1.

[0025] FIG. 5 is a plot showing the distribution of the tooth gingivitis and the tooth plaque scores for the subgingival plaque samples collected as described in Example 1, wherein lower scores represent healthier teeth.

[0026] FIG. 6 are graphs showing the linear regression analyses of Fusobacterium nucleatum with tooth plaque scores (left), tooth tartar scores (center), and tooth gingivitis scores (right), as described in Example 1 , wherein lower scores represent healthier teeth and RSME indicates the root mean square error.

[0027] FIG. 7 are graphs showing the linear regression analyses of Porphyromonas gingivalis with tooth plaque scores (left), tooth tartar scores (center), and tooth gingivitis scores (right), as described in Example 1 , wherein lower scores represent healthier teeth and RSME indicates the root mean square error.

[0028] FIG. 8 are graphs showing the linear regression analyses of Fusobacterium nucleatum with whole mouth plaque scores (left), whole mouth tartar scores (center), and whole mouth gingivitis scores (right), as described in Example 1 , wherein lower scores represent healthier teeth and RSME indicates the root mean square error.

[0029] FIG. 9 are graphs showing the linear regression analyses of Porphyromonas gingivalis with whole mouth plaque scores (left), whole mouth tartai’ scores (center), and whole mouth gingivitis scores (right), as described in Example 1, wherein lower scores represent healthier teeth and RSME indicates the root mean square error.

[0030] It should be understood that the various aspects of the disclosure are not limited to the compositions, arrangements, and instrumentality shown in the figures.

DETAILED DESCRIPTION

[0031] For illustrative purposes, the principles of the present disclosure are described by referencing various exemplary embodiments thereof. Although certain embodiments of the disclosure are specifically described herein, one of ordinary skill in the art will readily recognize that the same principles are equally applicable to, and can be employed in other compositions and methods. Before explaining the disclosed embodiments in detail, it is to be understood that the disclosure is not necessarily limited in its application to the details of any particular embodiment disclosed. The terminology used herein is for the purpose of description and not of limitation.

[0032] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless the context dictates otherwise. The singular form of any class of the ingredients refers not only to one ingredient within that class, but also to a mixture of those ingredients. The terms “a” (or “an”), “one or more” and “at least one” may be used interchangeably herein. The terms “comprising”, “including”, and “having” may be used interchangeably. The term “include” should be interpreted as “include, but are not limited to”. The term “including” should be interpreted as “including, but are not limited to”.

[0033] As used throughout, ranges are used as shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. Thus, a range from 1-5, includes specifically 1, 2, 3, 4 and 5, as well as subranges such as 2-5, 3-5, 2-3, 2-4, 1-4, etc. The term “about” when referring to a number means any number within a range of 10% of the number. For example, the phrase “about 2 wt.%” refers to a number between and including 1.8 wt.% and 2.2 wt.%.

[0034] All references cited herein are hereby incorporated by reference in their entireties. In the event of a conflict in a definition in the present disclosure and that of a cited reference, the present disclosure controls.

[0035] The abbreviations and symbols as used herein, unless indicated otherwise, take their ordinary meaning. The abbreviation “wt.%” means percent by weight with respect to the pet food composition. The symbol “°” refers to a degree, such as a temperature degree or a degree of an angle. The symbols “h”, “min”, “mL”,” nm”, “pm” means hour, minute, milliliter, nanometer, and micrometer, respectively. The abbreviation “UV-VIS” referring to a spectrometer or spectroscopy, means Ultraviolet-Visible. The abbreviation “rpm” means revolutions per minute.

[0036] Any member in a list of species that are used to exemplify or define a genus, may be mutually different from, or overlapping with, or a subset of, or equivalent to, or nearly the same as, or identical to, any other member of the list of species. Further, unless explicitly stated, such as when reciting a Markush group, the list of species that define or exemplify the genus is open, and it is given that other species may exist that define or exemplify the genus just as well as, or better than, any other species listed.

[0037] All components and elements positively set forth in this disclosure can be negatively excluded from the claims. In other words, the pet food compositions of the instant disclosure can be free or essentially free of all components and elements positively recited throughout the instant disclosure. In some instances, the compositions of the present disclosure may be substantially free of non-incidental amounts of the ingredient(s) or compound(s) described herein. A non-incidental amount of an ingredient or compound is the amount of that ingredient or compound that is added into the composition by itself. For example, a composition may be substantially free of a nonincidental amount of an ingredient or compound, although such ingredient(s) or compound(s) may be present as part of a raw material that is included as a blend of two or more compounds. Substantially free, unless otherwise defined or described herein, typically refers to an ingredient or compound in an amount of about 2 wt.% or less, about 1.5 wt.% or less, about 1 wt.% or less, about 0.5 wt.% or less, about 0.1 wt.% or less, or about 0.05 wt.% or less, about 0.01 wt.% or less, or about 0.001 wt.% or less, based on the total weight of the composition on a dry matter basis. [0038] Some of the various categories of components identified may overlap. Tn such cases where overlap may exist and the composition includes both components (or the composition includes more than two components that overlap), an overlapping compound does not represent more than one component. For example, certain components or ingredients may be characterized as both an ancient grain and an amaranth. If a particular composition recites both an ancient grain and an amaranth, a compound that may be characterized as both an ancient and an amaranth will serve only as either an ancient or an amaranth — not both.

[0039] As used herein, the term “pet” is used interchangeably with “companion animal” and refers to an animal of any species kept by a caregiver as a pet or any animal of a variety of species that have been widely domesticated as pets, including canines (Canis familiaris) and felines (Fells domesticus). Thus, a pet may include but is not limited to, working dogs, pet dogs, cats kept for rodent control (i.e., farm cats), pet cats, ferrets, birds, reptiles, rabbits, and fish.

[0040] To the extent that food and food ingredient contain water/moisture, the dry matter represents everything in the sample other than water including, for example, protein, fiber, fat, carbohydrates, minerals, etc. Dry matter weight is the total weight minus the weight of any water. The skilled artisan would readily recognize and understand nutritional amounts and percentages expressed as dry matter amounts, dry matter weights and dry matter percentages.

[0041] Dry matter intake per day is calculated as the total nutritional intake per day excluding all water. For example, an amount of an ingredient equal to a specific percent of daily nutritional intake refers to the amount of that ingredient in dry matter form (i.e., excluding all water) relative to the total amount of dry matter consumed (also excluding all water) in a day.

[0042] “Daily nutritional intake” and “total nutritional intake per day” refer to dry matter intake per day. That is, water weight is not included in calculating the amount of nutrition consumed per day. To calculate percent of an ingredient of total daily intake on a dry matter basis, water is removed from the total intake to give total daily dry matter intake and the percentage of the ingredient is based on amount of ingredient present as dry matter.

[0043] As used herein, an “ingredient” refers to any component of a composition. The term “nutrient” refers to a substance that provides nourishment and thus has a nutrient value. In some cases, an ingredient may comprise more than one “nutrient,” for example, a composition may comprise corn comprising important nutrients including both protein and carbohydrate. [0044] As used herein, the term “an effective amount” refers to the amount of a compound, material, or composition as described herein that may be effective to achieve a particular biological result, e.g., to treat, prevent, or alleviate periodontal disease, including conditions selected from dental plaque accumulation, calculus, tooth staining, gingivitis, periodontitis, stomatitis, halitosis, and combinations thereof. Such results may be achieved, for example, by feeding a composition of the present disclosure to an animal in need of such treatment.

[0045] As used herein, the term “coating” means a partial or complete covering, typically over a matrix of ingredients that covers at least a portion of a surface, for example a surface of a kibble. In one example, kibble may be partially covered with a coating such that only part of the kibble surface is covered, and in another example, the kibble may be completely covered with a coating. [0046] As used herein, the term “pet food composition” refers to a composition intended for ingestion by an animal, e.g., a dog or a cat. Such foods may be formulated as nutritionally balanced compositions suitable for daily feed and prepared as a dry food composition, e.g., a kibble, or they may be prepared as a dietary supplement or a treat, which may not necessarily be nutritionally balanced. As used herein, the term “kibble” includes a particulate pellet-like component of animal foods, which may range in texture from hard to soft and may have internal structures ranging from expanded structures to dense structures. Kibbles may be formed by an extrusion process.

[0047] As used herein, the term “dentifrice” refers to a paste, gel, liquid or solid composition for oral care, such as the oral care of a companion animal. In some embodiments, a dentifrice composition can be a combination of pastes, gels, or paste and gel. In some embodiments, a dentifrice composition is a toothpaste, and in some embodiments the dentifrice composition is a mouthwash or dental rinse.

[0048] Aspects of the disclosure are directed to compositions, including pet food compositions and dentifrices, and methods of use thereof for treating, preventing, or alleviating periodontal disease, as well as methods of reducing plaque and tartar accumulation and/or improving the oral health of a companion animal. In embodiments of the disclosure, the composition disclosed herein comprises D-ribose.

[0049] D-ribose is simple sugar and an essential component of adenosine triphosphate (ATP), which provides energy to host body cells. In addition, D-ribose acts as a quorum sensing inhibitor. Specifically, D-ribose inhibits autoinducer 2, a universal quorum sensing molecule that mediates intergeneric signaling in multispecies bacterial communities to induce and maintain biofilm creation. D-ribose has shown inhibitory properties toward the quorum sensing molecule autoinduccr 2 in in vitro biofilm assays and coaggregation cultures of both Fusobacterial nucleatum and Porphyromonas gingivalis. Thus, without wishing to be bound by theory, it is believed that the D-ribose present in the compositions disclosed herein acts to inhibit and/or reduce biofilm formation by modulating potential pathogenic bacterial species, thereby preventing periodontal disease, such as gingivitis and periodontitis.

[0050] Bacteria play a significant role in the etiology of periodontal disease by building plaque biofilm, and subsequent accumulation of specific pathogenic bacterial species are key in the activation of the host inflammatory response. As the plaque buildup extends from the gingival margin to the subgingival sulcus, the anaerobic environment helps proliferate certain anaerobic bacterial species, including pathogenic species that are late colonizers. The persistence of these late colonizers can cause inflammation in gingival tissues (gingivitis) and induce the host’s immune response. Periodically disturbing the plaque buildup and maturation process helps to prevent gingivitis and periodontitis. This period disturbance can be accomplished by mechanical means, such as brushing, scaling, dental chews, and fiber-based technologies, and/or by chemical means, such as through polyphosphates, antibiotics, and biofilm degraders. In addition, specifically targeting the prevention of late colonizers by using specialty ingredients, e.g., D- ribose, may help to treat, prevent, and/or alleviate the symptoms of periodontal disease.

[0051] Late colonizers may be grouped into “Orange complex” and “Red complex” bacterial species. “Orange complex” species of bacteria include three species: Fusobacterium nucleatum, Campylobacter rectus, and Prevotella intermedia. Fusobacterium nucleatum is believed to play a role in halitosis, dental pulp infection, and potentially oral cancer, and is recognized as a prime species in the development of periodontitis by creating favorable conditions with the priority of decreasing host neutrophil efficiency. Fusobacterium nucleatum also acts as a “bridging species,” metabolically connecting with “Red complex” species. One such “Red complex species is Porphyromonas gingivalis, a main causative agent found in the subgingival plaque of patients with periodontal disease. Accordingly, disturbance in the persistence of Fusobacterium nucleatum, for example through a composition as disclosed herein comprising D-ribose, would help to limit the establishment of Porphyromonas gingivalis and thereby treat, prevent, and/or alleviate the symptoms of various periodontal diseases, including gingivitis. [0052] Accordingly, disclosed herein is a composition comprising D-ribose. In certain embodiments, the composition (c.g., pct food composition or dentifrice) may comprise D-ribosc in an amount effective to treat, prevent, and/or alleviate the symptoms of various periodontal diseases, including gingivitis. In certain embodiments, the composition disclosed herein comprises D-ribose in an amount ranging from about 0.5 wt.% to about 10 wt.%, such as from about 0.5 wt.% to about 5 wt.%, about 0.5 wt.% to about 4.5 wt.%, about 0.5 wt.% to about 4 wt.%, about 0.5 wt.% to about 3.5 wt.%, about 0.5 wt.% to about 3 wt.%, about 0.5 wt.% to about 2.5 wt.%, or about 0.5 wt% to about 2 wt%; from about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4.5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3.5 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2.5 wt.%, or about 1 wt% to about 2 wt%; from about 1.5 wt.% to about 5 wt.%, from about 1.5 wt.% to about 4.5 wt.%, from about 1.5 wt.% to about 4 wt.%, about 1.5 wt.% to about 3.5 wt.%, about 1.5 wt.% to about 3 wt.%, about 1.5 wt.% to about 2.5 wt.%, or about 1.5 wt.% to about 2 wt.%; or about 2 wt.%, by weight based on the total weight of the composition.

[0053] In some embodiments, the composition is formulated to comprise D-ribose as the only added sugar in the composition. For example, in certain embodiments the composition is free or substantially free of any other added sugar, such as free of dextrose, glucose, galactose, fructose, sucrose, lactose, maltose, arabinose, xylose, mannose, erythrose, and/or threose.

[0054] Suitable components, such as those listed below, may be included or excluded from the formulations for the compositions disclosed herein depending on the specific combination of other ingredients and the form of the compositions. In some embodiments, the pet food compositions disclosed herein may be in the form of a stand-alone pet food, as a supplement to pet food, as a pet food treat, or the like. In certain embodiments, the pet food composition disclosed herein may comprise protein, carbohydrates, fat, and fiber.

[0055] In certain embodiments, the pet food compositions of the disclosure include protein. Protein may be supplied by any of a variety of sources known by those of ordinary skill in the art including plant sources, animal sources, microbial sources or a combination of these. For example, animal sources may include meat, meat-by products, seafood, dairy, eggs, etc. Meats, for example, may include animal flesh such as poultry, fish, and mammals including cattle, pigs, sheep, goats, and the like. Meat by-products may include, for example, lungs, kidneys, brain, livers, stomachs and intestines. Plant protein includes, for example, soybean, cottonseed, and peanuts. Microbial sources may be used to synthesize amino acids (e.g., lysine, threonine, tryptophan, methionine) or intact protein such as protein from sources listed herein.

[0056] The protein the pet food compositions disclosed herein may be present in an amount that may vary. For instance, the pet food composition may include protein in an amount ranging from about 15 wt.% to about 55 wt.%, based on the total weight of the pet food composition on a dry matter basis. In some embodiments, the amount of protein present in the pet food composition is from about 15 wt.% to about 50 wt.%, about 15 wt.% to about 45 wt.%, about 15 wt.% to about 40 wt.%, about 15 wt.% to about 35 wt.%, about 15 wt.% to about 30 wt.%; about 20 wt.% to about 55 wt.%, about 20 wt.% to about 50 wt.%, about 20 wt.% to about 45 wt.%, about 20 wt.% to about 40 wt.%, about 20 wt.% to about 35 wt.%, about 20 wt.% to about 30 wt.%; from about 23 wt.% to about 55 wt.%, about 23 wt.% to about 50 wt.%, about 23 wt.% to about 45 wt.%, about 23 wt.% to about 40 wt.%, about 23 wt.% to about 35 wt.%; from about 26 wt.% to about 55 wt.%, about 26 wt.% to about 50 wt.%, about 26 wt.% to about 45 wt.%, about 26 wt.% to about 40 wt.%, about 26 wt.% to about 35 wt.%; from about 29 wt.% to about 55 wt.%, about 29 wt.% to about 50 wt.%, about 29 wt.% to about 45 wt.%, about 29 wt.% to about 40 wt.%, about 29 wt.% to about 35 wt.%; from about 32 wt.% to about 55 wt.%, about 32 wt.% to about 50 wt.%, about 32 wt.% to about 45 wt.%, about 32 wt.% to about 40 wt.%; from about 35 wt.% to about 55 wt.%, about 35 wt.% to about 50 wt.%, about 35 wt.% to about 45 wt.%, about 35 wt.% to about 40 wt.%; from about 38 wt.% to about 55 wt.%, about 38 wt.% to about 50 wt.%, about 38 wt.% to about 45 wt.%; from about 41 wt.% to about 55 wt.%, about 41 wt.% to about 50 wt.%; or from about 43 wt.% to about 55 wt.%, including ranges or subranges thereof, based on the total weight of the pet food composition on a dry matter basis.

[0057] Examples of protein or protein ingredients may comprise chicken meals, chicken, chicken by-product meals, lamb, lamb meals, turkey, turkey meals, beef, beef by-products, viscera, fish meal, enterals, kangaroo, white fish, venison, soybean meal, soy protein isolate, soy protein concentrate, com gluten meal, corn protein concentrate, distillers dried grains, and/or distillers dried grain solubles and single-cell proteins, for example yeast, algae, and/or bacteria cultures.

[0058] The pet food compositions of the disclosure may also comprise free amino acids, peptides, and combinations thereof. The amino acids may be selected from Tryptophan, Taurine, Histidine, Carnitine, Carnosine, Alanine, Cysteine, Arginine, Methionine (including DL-methionine, and L- methionine), Tryptophan, Lysine, Asparagine, Aspartate (Aspartic acid), Phenylalanine, Valine, Threonine, Isoleucine, Histidine, Leucine, Glycine, Glutamine, Taurine, Tyrosine, Homocysteine, Ornithine, Citrulline, Glutamate (Glutamic acid), Proline, and/or Serine, and a combination of two or more thereof. In some cases, the one or more amino acid(s) may comprise essential amino acids. Essential amino acids are amino acids that cannot be synthesized de novo, or in sufficient quantities by an organism and thus must be supplied in the diet. Essential amino acids vary from species to species, depending upon the organism’s metabolism. For example, it is generally understood that the essential amino acids for dogs and cats (and humans) are phenylalanine, leucine, methionine, lysine, isoleucine, valine, threonine, tryptophan, histidine and arginine. In addition, taurine, while technically not an amino acid but a derivative of cysteine, is an essential nutrient for cats.

[0059] The pet food compositions of the disclosure may further comprise one or more sources of fat and/or carbohydrate, including those known to those in the art. Illustrative examples of suitable sources of carbohydrate and fat include, but are not to be limited to, animal fat, fish oil, vegetable oil, meat, meat by-products, grains, other animal or plant sources, and mixtures thereof Grains include wheat, sorghum, com, barley, rice and the like.

[0060] The pet food composition may in certain embodiments contain carbohydrates in an amount of about 70 wt.% or less, based on the total weight of the pet food composition on a dry matter basis. In some embodiments, the pet food compositions have an amount of carbohydrates ranging from about 5 wt.% to about 65 wt.%, such as from about 25 wt.% to about 50 wt.%, from about 30 wt.% to about 50 wt.%, from about 35 wt.% to about 50 wt.%, from about 40 wt.% to about 50 wt.%, from about 45 wt.% to about 50 wt.%, or from about 47 wt.% to about 50 wt.%, based on the total weight of the pet food composition on a dry matter basis.

[0061] The term “carbohydrate” as used herein includes polysaccharides (e.g., starches and dextrins) and sugars (e.g., sucrose, lactose, maltose, glucose, and fructose) that are metabolized for energy when hydrolyzed. Generally, carbohydrate percentage can be calculated as nitrogen free extract (“NFE”), which can be calculated as follows: NFE %=100%-(moisture %)-(protein %)-(fat %)-(ash %)-(crude fiber %). One skilled in the art could manipulate the texture of the final product by properly balancing carbohydrate sources. For example, short chain polysaccharides tend to be sticky and gluey, and longer chain polysaccharides tend to be less sticky and gluey than the shorter chain. The desired texture of a pet food may therefore be achieved by addition of a desirable amount longer chain polysaccharide and modified starches such as native or modified starches, cellulose and the like. The carbohydrate mixture may additionally comprise optional components such as added salt, spices, seasonings, vitamins, minerals, flavorants, colorants, and the like. The amount of the optional components may at least partially depend on the nutritional requirements for different life stages of animals.

[0062] Carbohydrates can be supplied by any of a variety of sources known by those skilled in the art, including, but not limited to, oat fiber, cellulose, peanut hulls, beet pulp, parboiled rice, cornstarch, corn gluten meal, cereal, and sorghum. Grains supplying carbohydrates can include, but are not limited to, wheat, durum, semolina, corn, barley, and rice. In certain embodiments, the carbohydrate component comprises a mixture of one or more carbohydrate sources. Carbohydrates content of foods can be determined by any number of methods known by those of skill in the art. [0063] In some cases, the fat in the pet food composition is a crude fat. Crude fat may be included into the compositions in any amount known in the art, such as from about 2 wt.% to about 50 wt.%, based on the total weight of the pet food composition on a dry matter basis. In some embodiments, the pet food composition comprises crude fat in an amount of about 2 wt.% to about 40 wt.%, about 2 wt.% to about 35 wt.%, about 2 wt.% to about 30 wt.%, about 2 wt.% to about 25 wt.%, about 2 wt.% to about 20 wt.%, about 2 wt.% to about 15 wt.%, about 5 wt.% to about 35 wt.%, about 5 wt.% to about 30 wt.%, about 5 wt.% to about 25 wt.%, about 5 wt.% to about 20 wt.%, about 5 wt.% to about 15 wt.%, about 10 wt.% to about 35 wt.%, about 10 wt.% to about 30 wt.%, about 10 wt.% to about 25 wt.%, about 10 wt.% to about 20 wt.%, about 10 wt.% to about 15 wt.%, or about 11 wt.% to about 15 wt.%, based on the total weight of the pet food composition on a dry matter basis. In some cases, it may be preferable that about 50 wt.% or more, about 60 wt.% or more, about 70 wt.% or more, about 80 wt.% or more, or about 90 wt.% or more of the total fat is obtained from an animal source. Alternatively, about 50 wt.% or more, about 60 wt.% or more, about 70 wt.% or more, about 80 wt.% or more, or about 90 wt.% or more of the total fat may be obtained from a plant source.

[0064] The pet food compositions of the disclosure may also comprise one or more types of fiber, which may be classified as soluble or insoluble fiber. Illustrative but non-limiting sources of fiber include wherein the fiber food ingredient is obtained from a variety of sources such as vegetable fiber sources, for example, cellulose, beet pulp, peanut hulls, and soy fiber.

[0065] The pet food compositions disclosed herein may be formulated to include fiber in an amount ranging from about 2 wt.% to about 50 wt.%, based on the total weight of the pet food composition on a dry matter basis. For instance, the amount of fiber present in the pet food composition may be from about 2 wt.% to about 45 wt.%, about 2 wt.% to about 40 wt.%, about 2 wt.% to about 35 wt.%, about 2 wt.% to about 20 wt.%, about 5 wt.% to about 45 wt.%, about 5 wt.% to about 40 wt.%; from about 5 wt.% to about 35 wt.%, about 5 wt.% to about 30 wt.%, about 5 wt.% to about 25 wt.%, about 5 wt.% to about 20 wt.%, about 8 wt.% to about 45 wt.%, about 8 wt.% to about 40 wt.%, about 8 wt.% to about 35 wt.%; from about 8 wt.% to about 30 wt.%, about 8 wt.% to about 25 wt.%, about 8 wt.% to about 20 wt.%, or about 8 wt.% to about 17 wt.%, including ranges and subranges thereof, based on the total weight of the pet food composition on a dry matter basis.

[0066] Dietary fiber refers to components of a plant that are resistant to digestion by an animal’s digestive enzymes. Dietary fiber includes soluble fiber and insoluble fiber. Soluble fibers are resistant to digestion and absorption in the small intestine and undergo complete or partial fermentation in the large intestine, e.g., beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, squash, apples, oats, beans, citrus, barley, or peas. Insoluble fibers can be supplied by any of a variety of sources, including, for example, cellulose, whole-wheat products, wheat oat, com bran, flax seed, grapes, celery, green beans, cauliflower, potato skins, fruit skins (e.g., pear skin), vegetable skins, peanut hulls, almond shell, walnut shell, pecan shell, citrus pulp, beet pulp, and soy fiber. In some embodiments, the dietary fiber may be chosen from pecan shell, citrus pulp, beet pulp, and a combination of two or more thereof. Crude fiber includes indigestible components contained in cell walls and cell contents of plants such as grains, for example, hulls of grains such as rice, corn, and beans.

[0067] In certain embodiments, the pet food compositions of the disclosure may also comprise nutritional balancing agents that are obtained from a variety of sources known to skilled artisans, for example, vitamin and mineral supplements and food ingredients. Vitamins and minerals can be included in amounts required to avoid deficiency and maintain health. These amounts are readily available in the art. The Association of American Feed Control Officials (AAFCO) provides recommended amounts of such nutrients for dogs and cats. See Association of American Feed Control Officials, Inc., Official publication, pp. 159-162 (2011). Vitamins generally useful as food additives include vitamin A, vitamin Bi, vitamin B2, vitamin Be, vitamin B12, vitamin D, biotin, vitamin K, folic acid, inositol, niacin, and pantothenic acid. Minerals and trace elements useful as food additives include calcium, phosphorus, sodium, potassium, magnesium, copper, zinc, chloride, iron, selenium, iodine, and iron. [0068] In certain other embodiments, the pet food compositions of the disclosure may contain other ingredients, in addition to vitamins and minerals, such as fillers, palatability enhancers, binding agents, flavors, stabilizers, emulsifiers, sweeteners, colorants, buffers, salts, coatings, and the like known to skilled artisans. Stabilizers include substances that tend to increase the shelf life of the composition such as preservatives, synergists and sequestrants, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and humectants. Examples of emulsifiers and/or thickening agents include gelatin, cellulose ethers, starch, starch esters, starch ethers, and modified starches. Specific amounts for each composition component, food ingredient, and other ingredients will depend on a variety of factors such as the particular components and ingredients included in the composition; the species of animal; the animal's age, body weight, general health, sex, and diet; the animal's consumption rate; the type of disease or condition being treated; and the like. Therefore, the component and ingredient amounts may vary widely and may deviate from the preferred proportions described herein.

[0069] In certain embodiments, the pet food composition comprises moisture. The moisture may be present at various amounts or concentrations. In one embodiment, moisture may be present in an amount of from about 3 wt.% to about 20 wt.%, based on the total weight of the pet food composition. For example, moisture may be present in an amount of about 3 wt.%, about 5 wt.%, about 5.5 wt.%, about 6 wt.%, about 6.5 wt.%, about 7 wt.%, about 7.5 wt.%, about 8 wt.%, about

8.5 wt.%, about 9 wt.%, about 9.5 wt.%, about 10 wt.%, about 10.5 wt.%, about 11 wt.%, about

11.5 wt.%, about 12 wt.%, about 12.5 wt.%, about 13 wt.%, about 13.5 wt.%, about 14 wt.%, about

14.5 wt.%, or about 15 wt.%, based on the total weight of the pet food composition. In another example, moisture may be present in an amount of from about 6 wt.% to about 12 wt.%, about 9 wt.% to about 13 wt.%, about 9 wt.% to about 11 wt.%, or about 9 wt.% to about 13 wt.%, based on the total weight of the pet food composition. In certain embodiments, moisture is present in an amount of about 5 wt.% to about 12 wt.%, about 6 wt.% to about 11 wt.%, or about 7 wt.% to about 10 wt.%, based on the total weight of the pet food composition. In further embodiments, moisture is present in an amount of about 65 wt.% to about 85 wt.%, about 60 wt.% to about 80 wt.%, or about 60 wt.% to about 75 wt.%, based on the total weight of the pet food composition.

[0070] The pet food compositions disclosed herein may be wet or dry compositions, and the ingredients, including for example the D-ribose, can be either incorporated into the food composition and/or on the surface of any composition component, such as, for example, by spraying, agglomerating, dusting, or precipitating on the surface. Additionally, the pet food compositions may be formulated and produced to be in various forms and/or consistencies. For instance, the pet food compositions may, for example, be a dry, moist or semi-moist animal food composition. “Semi-moist” refers to a food composition containing from about 25% to about 35% moisture. “Moist” food refers to a food composition that has a moisture content of about 60% to 90% or greater. “Dry” food refers to a food composition with about 3% to about 12% moisture content and is often manufactured in the form of small bits or kibbles.

[0071] The food products may also include components of more than one consistency, for example, soft, chewy meat-like particles or pieces as well as kibble having an outer coating and an inner “core” component. In some embodiments, the pet food compositions may be in the form of a kibble or food kibble. In some embodiments, a food kibble has a moisture, or water, content of less than 15% by weight. Food kibbles may range in texture from hard to soft. Food kibbles may range in internal structure from expanded to dense. Food kibbles may be formed by an extrusion process or a baking process. In non-limiting examples, a food kibble may have a uniform internal structure or a varied internal structure. For example, a food kibble may include a core and a coating to form a coated kibble. It should be understood that when the term “kibble” or “food kibble” is used, it can refer to an uncoated kibble or a coated kibble.

[0072] The composition of the present disclosure can additionally comprise other additives in amounts and combinations familial' to one of skill in the ail. Such additives should be present in amounts that do not impair the purpose and effect provided by the invention. Examples of additives include substances with a stabilizing effect, organoleptic substances, processing aids, and substances that provide nutritional benefits.

[0073] Stabilizing substances may include, by way of example, substances that tend to increase the shelf life of the pet food composition. Other examples of other such additives potentially suitable for inclusion in the compositions of the invention include, for example, preservatives, antioxidants, synergists and sequestrants, packaging gases, stabilizers, emulsifiers, thickeners, gelling agents, and humectants. Examples of emulsifiers and/or thickening agents include gelatin, cellulose ethers, starch, starch esters, starch ethers, and modified starches. Additives for coloring, palatability, and nutritional purposes can include colorants, salts (including, but not limited to, sodium chloride, potassium citrate, potassium chloride, and other edible salts), vitamins, minerals, and flavoring. Other additives can include glucosamine, chondroitin sulfate, vegetable extracts, herbal extracts, etc.

[0074] The concentration of such additives in the pet food composition typically can be up to about 5 wt.%, based on the total weight of the pet food composition on a dry matter basis. For example, the additives may be present in an amount from about 0.01 wt.% to about 5 wt.%, about 0.01 wt.% to about 4 wt.%, about 0.01 wt.% to about 4 wt.%, about 0.01 wt.% to about 3 wt.%, about 0.01 wt.% to about 2 wt.%, about 0.01 wt.% to about 1 wt.%; about 0.1 wt.% to about 5 wt.%, about 0.1 wt.% to about 4 wt.%, about 0.1 wt.% to about 4 wt.%, about 0.1 wt.% to about 3 wt.%, about 0.1 wt.% to about 2 wt.%, about 0.1 wt.% to about 1 wt.%; about 1 wt.% to about 5 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 4 wt.%, about 1 wt.% to about 3 wt.%, about 1 wt.% to about 2 wt.%; about 2 wt.% to about 5 wt.%, about 2 wt.% to about 4 wt.%, about 2 wt.% to about 4 wt.%, about 2 wt.% to about 3 wt.%; about 3 wt.% to about 5 wt.%, about 3 wt.% to about 4 wt.%; or about 4 wt.% to about 5 wt.%, based on the total weight of the pet food composition on a dry matter basis.

[0075] In specific embodiments, the pet food compositions and food products are formulated to address specific nutritional differences between species and breeds of animals, as well as one of more of the attributes of the animal. For example, cat foods, for example, are typically formulated based upon the life stage, age, size, weight, body composition, and breed.

[0076] The pet food compositions may include, or in some instance exclude, one or more ingredients selected from beef broth, brewers dried yeast, egg, egg product, flax meal, DL methionine, amino acids, leucine, lysine, arginine, cysteine, cystine, aspartic acid, polyphosphates, sodium pyrophosphate, sodium tripolyphosphate; zinc chloride, copper gluconate, stannous chloride, stannous fluoride, sodium fluoride, triclosan, glucosamine hydrochloride, chondroitin sulfate, green lipped mussel, blue lipped mussel, methyl sulfonyl methane (MSM), boron, boric acid, phytoestrogens, phytoandrogens, genistein, diadzein, L-carnitine, chromium picolinate, chromium tripicolinate, chromium nicotinate, acid/base modifiers, potassium citrate, potassium chloride, calcium carbonate, calcium chloride, sodium bisulfate; eucalyptus, lavender, peppermint, plasticizers, colorants, Ilavorants, sweeteners, buffering agents, slip aids, carriers, pH adjusting agents, natural ingredients, stabilizers, biological additives such as enzymes (including proteases and lipases), chemical additives, coolants, chelants, denaturants, drug astringents, emulsifiers, external analgesics, fragrance compounds, humectants, opacifying agents (such as zinc oxide and titanium dioxide), antifoaming agents (such as silicone), preservatives (such as butylated hydroxytolucnc (BHT) and butylated hydroxy anisole (BHA), propyl gallate, benzalkonium chloride, EDTA, benzyl alcohol, potassium sorbate, parabens and mixtures thereof), reducing agents, solvents, hydrotropes, solubilizing agents, suspending agents (non-surfactant), solvents, viscosity increasing agents (aqueous and non-aqueous), sequestrants, keratolytics, egg shell membrane, ancient grain, and a combination of two or more thereof.

[0077] The pet food composition may be produced by various methods to achieve the desired pet food composition or desired form for the pet food composition. For example, dry food may be baked or extruded, then cut into individual shaped portions, such as kibbles. In some embodiments, the pet food composition may be prepared in a canned or wet form using conventional food preparation processes known to those of ordinary skill in the ail. Typically, ground animal proteinaceous tissues are mixed with the other ingredients, such as cereal grains, suitable carbohydrate sources, fats, oils, and balancing ingredients, including special purpose additives such as vitamin and mineral mixtures, inorganic salts, cellulose, beet pulp and the like, and water in an amount sufficient for processing. The ingredients are mixed in a vessel suitable for heating while blending the components. Heating the mixture is carried out using any suitable manner, for example, direct steam injection or using a vessel fitted with a heat exchanger. Following addition of all of the ingredients of the formulation, the mixture may be heated to a temperature of from 50 °F to 212 °F. Although temperatures outside this range can be used, they may be commercially- impractical without the use of other processing aids. When heated to the appropriate temperature, the material will typically be in the form of thick liquid, which is dispensed into cans. A lid is applied and the container is hermetically sealed. The sealed can is then placed in convention equipment designed for sterilization of the contents. Sterilization is usually accomplished by heating to temperatures of greater than 230 °C for an appropriate time depending on the temperature used, the nature of the composition, and related factors. The pet food compositions and food products of the present disclosure can also be added to or combined with food compositions before, during, or after their preparation.

[0078] In some embodiments, the pet food compositions disclosed herein may be prepared in a dry form using convention processes known to those of ordinary skill in the art. Typically, dry ingredients, including dried animal protein, plant protein, grains and the like are ground and mixed together. Liquid or moist ingredients, including fats, oils water, animal protein, water, and the like are added combined with the dry materials. The specific formulation, order of addition, combination, and methods and equipment used to combine the various ingredients can be selected from those known in the ail. For example, in certain embodiments, the resulting mixture is process into kibbles or similar dry pieces, which are formed using an extrusion process in which the mixture of dry and wet ingredients is subjected to mechanical work at high pressure and temperature, forced through small openings or apertures, and cut off into the kibbles, e.g., with a rotating knife. The resulting kibble can be dried and optionally coated with one or more topical coatings comprising, e.g., flavors, fats, oils, powdered ingredients, and the like. Kibbles may also be prepared from dough by baking, rather than extrusion, in which the dough is placed into a mold before dry-heat processing.

[0079] In preparing a composition, any ingredient generally may be incorporated into the composition during the processing of the formulation, e.g., during and/or after mixing of the other components of the composition. Distribution of these components into the composition can be accomplished by conventional means. In certain embodiments, ground animal and/or poultry proteinaceous tissues are mixed with other ingredients, including nutritional balancing agents, inorganic salts, and may further include cellulose, beet pulp, bulking agents and the like, along with sufficient water for processing.

[0080] In some embodiments, ingredients of the pet food composition disclosed herein are extruded, and then a surface coating comprising D-ribose and optionally a palatant and/or other coating ingredients is applied. In some embodiments, the kibble is spray coated in a tumbling mixer with a composition comprising D-ribose and optionally a palatant and/or other coating ingredients. In other embodiments, the kibble is coated with a coating comprising D-ribose using a vacuum enrobing technique, wherein the kibble is subjected to vacuum and then exposed to coating materials after which the release of the vacuum drives the coating materials inside the kibble. In certain embodiments, the uncoated kibble comprises D-ribose, and the uncoated kibble may either remain uncoated or may be subsequently, e.g., with a palatant, by any of the means disclosed herein.

[0081] In accordance with certain embodiments, further disclosed herein is a method for treating, preventing and/or alleviating periodontal disease in a companion animal, the method comprising administering to a companion animal in need thereof a composition as disclosed herein. [0082] In accordance with another aspect, provided is a method for reducing plaque and/or tartar in a companion animal, the method comprising administering to a companion animal in need thereof a composition disclosed herein.

[0083] According to yet another embodiment, disclosed herein is a method of reducing the abundance of at least one of Fusobacterium nucleatum or Porphyromonas gingivalis in the oral cavity of a companion animal, the method comprising administering to a companion animal in need thereof a composition disclosed herein.

[0084] Any of the methods disclosed herein may include providing and/or feeding the companion animal, e.g., a canine, a pet food composition as disclosed herein. In some instances, the method may include providing and/or feeding the companion animal the pet food compositions for 1 or more days, preferably 5 or more days, preferably 7 or more days, preferably 10 or more days, preferably 14 or more days, preferably 30 or more days, or preferably 42 or more days. The method may include feeding the companion animals one time a day, two times a day, three times a day, or in some embodiments four or more times a day.

[0085] Additionally or alternatively, any of the methods disclosed herein may include providing and/or applying to the oral cavity of companion animal, e.g., a canine, a dentifrice as disclosed herein. In some instances, the dentifrice is applied to the oral cavity of the companion animal for 1 or more days, preferably 5 or more days, preferably 7 or more days, preferably 10 or more days, preferably 14 or more days, preferably 30 or more days, or preferably 42 or more days. The method may include applying the dentifrice to the oral cavity of the companion animals one time a day, two times a day, once a week day, twice a week, three times a week, four times a week, or once a month.

[0086] The examples and other embodiments described herein are exemplary and not intended to be limiting in describing the full scope of compositions and methods of this disclosure. Equivalent changes, modifications and variations of specific embodiments, materials, compositions and methods may be made within the scope of the present disclosure, with substantially similar results.

EXAMPLES

Example 1

[0087] Four exemplary pet food compositions were prepared in accordance with aspects of the disclosure as follows: (1) a negative control food; (2) a positive control food; (3) Test food 1; and (4) Test food 2, wherein all four foods were formulated according to AAFCO nutritional recommendations and were in the form of kibbles generated by extrusion method. The negative control food had neither mechanical nor chemical components to effect disruption of plaque building, and was dried after extrusion and coated with palatants. The positive control food was a kibble that was dried after extrusion and coated with palatants. Unlike the negative control food and either Test Food 1 or Test Food 2, the positive control food was produced following a method having transverse, fibrous striated matrix that provides mechanical cleaning action (to mimic brushing) with a previously-proven reduction in plaque building. The Test Food 1 was dried after extrusion and coated with palatants, and formulated with a prebiotic fiber bundle, containing pecan shell fiber, cranberry pomace, citrus pulp, beet pulp, and flax seed. The Test Food 2 was formulated to include 2% D-ribose, which was first mixed with a liquid palatant and whisked thoroughly before coating to the extruded and dried kibble. The four pet food compositions and their predicted proximate analyses are shown below in Tables 1 and 2, respectively.

[0088] Table 1 - Formulations of pet food compositions

[0089] Table 2 - Nutrient analysis (predicted by PDM) of pet food compositions

[0090] This feeding study was performed on a total of 20 clinically healthy (based on blood CBC/serum chemistry and urinalysis) adult dogs having a body weight ranging from 12.59 to 22.66 kg and an age at the start of the trial ranging from 4 years, 7 months to 7 years, 11 months. All dogs were of mixed gender and reproductive status (intact, neutered, or spayed). Briefly, the 20 dogs were randomly assigned into four groups of 5 dogs each based on their gender, age and whole mouth plaque scores, as measured before the feeding study started and which was consider as a baseline. The feeding study was performed using a William’s Latin Square design, as shown in Figure 1 , such that each of the subjects received each of the four food compositions for a total of 28 days.

[0091] Before starting the feeding trial, full mouth dental prophylaxis (supra- and subgingival on the buccal and lingual sides) and dental examination was conducted. Biofilm removal at supragingival and subgingival level was confirmed with the use of eosin dye or dental flashlight during prophylaxis.

[0092] After dental prophylaxis, each group was fed the diets following the sequence as described in Figure 1, and each diet was fed for a period of 28 days. On Day 28, dogs were graded under anesthesia using the Logan-Boyce method for dental plaque and calculus. Whole mouth plaque and calculus accumulation was quantified using the Veterinary Oral Health Council metrics and those outlined below, applied to the “whole tooth” (no splitting for plaque and calculus). Each tooth dental plaque was scored based on the coverage and the thickness (eosin stain intensity) using the numerical score as follows: Coverage: 0 = no plaque detected; 1 = 1-24%; 2 = 25-49%; 3 = 50-74%; and 4 = 75-100%. Thickness: 1 = light; pink to light red; and 2 = medium, red. Each tooth calculus was scored based on the coverage using the numerical score as follows: Coverage 0 = no calculus detected; 1 = 1-24%; 2 = 25-49%; 3 = 50-74%; and 4 = 75-100%. Each tooth gingivitis score was measured based on the Loe & Silness method, using the following metrics: 0 = normal gingiva, 0.5 = mild inflammation with slight redness, 1 = moderate inflammation and redness, but no bleeding on probing, 2 = moderate inflammation with severe redness and bleeding on probing, and 3 = severe inflammation and redness, edema, ulceration and spontaneous bleeding. Whole mouth plaque, calculus, and gingivitis mean score was calculated by averaging the total teeth scores for each animal. After the dental grading, all dogs underwent full mouth dental prophylaxis followed by another diet fed for another 28 days, and so on to complete the sequence as shown in Figure 1. The four diets described above in Tables 1 and 2 were used in this study. All dogs were allowed their routine activities, except they were not allowed to have chew toys or treats.

[0093] Subgingival plaque sample collection: Sub-gingival plaque samples were collected for microbiome analyses. For every subject, subgingival plaque samples were collected from both healthy and unhealthy teeth on each dog. Healthy and unhealthy teeth were confirmed based on individual tooth gingivitis scores. A tooth gingivitis score of “0 = normal gingiva” was considered as a healthy tooth and a tooth gingivitis score of 0.5 or greater was considered an unhealthy tooth. If the subject did not have any unhealthy teeth, then the subgingival plaque samples were collected from two different healthy teeth. Likewise, if the subject did not have any healthy teeth, then the subgingival plaque samples were collected from two different unhealthy teeth.

[0094] Subgingival plaque samples were analyzed for microbiome sequencing by extracting total DNA from frozen samples by using Qiagen DNeasy Power Biofilm extraction kit. Following total DNA extraction, 16s rDNA amplicon was developed from the samples by employing PCR using the primer sets spanning the VI and V3 hypervariable regions, and the amplicons were subsequently analyzed qualitatively by an Agilent 2100 Bioanalyzer. Further, index PCR was performed, followed by library quantification, normalization and pooling the samples by following manufacturer’s instructions with modifications. The final pooled sample library was loaded in a MiSeq v3 sample loading cartridge kit, and the cartridge was placed in a MiSeq (Illumina) sequencer for sequencing the amplicons. The sample sequences were demultiplexed by using MiSeq’s in-built metagenomics workflow to obtain FASTQ files. FASTQ Files were processed by employing Mothur software to classify the sequence reads using Human Oral Microbiome Database (HOMD v.15.11) followed by custom modifications.

[0095] Data filtering and statistical analysis: For the microbiome analyses, the abundance data was filtered by prevalence (OTUs representing >25% of samples in the dataset) and by reads coverage (>98.0% of sequencing reads retained per sample; reads per sample 83,558.86 ± 42,799.45). After filtering, the count data were transformed into centered log-ratio (CLR) values to enable statistical analysis appropriate for compositional data. The study was a crossover design, and therefore the mixed model analysis was performed using food type as the fixed effect and animal identification as a random effect to account for repeated measures with false discovery rate (FDR)-corrected P values by employing JMP Pro v.17.0. Tukey’s post hoc test was used to assess pairwise differences across diet types for each variable.

[0096] Results: Based on the mixed model analyses, the “food effect” showed a significance (p = < 0.0001), but no significance was observed for the “food fed sequence effect” for whole mouth plaque scores. The Tukey post-hoc significance test baseline showed higher whole mouth plaque scores compared with other foods. For whole mouth plaque scoring, the dogs fed the positive control food showed the highest significant reduction, followed by the Test Food 2 and then the Test Food 1 and the baseline, as shown in Figure 2. While not wishing to be bound by theory, it is believed that the highest reduction in whole mouth plaque score observed with the positive control food was due to the mechanical effect provided by the kibble, as discussed above and as developed with a specialized food processing method. Likewise, the finding support the conclusion that the significant reduction in whole mouth scores demonstrated by the Test Food 2 were due to the chemical effect provided by the inclusion of D-ribose added at the coating stage of the finished kibble. Overall, Test Food 2 showed a significant reduction of whole mouth plaque scores compared to the negative control food and the Test Food 1.

[0097] In addition to reducing whole mouth plaque scores, the dogs fed the Test Food 2 also showed a non- significant decreasing trend line in the abundance levels of specific microbial species, including Fusobacterium nucleatum, subsp. vincentii and Porphyromonas gingivalis in subgingival plaque, as compared to dogs fed other food compositions, as shown in Figure and Figure 4. Fusobacterial nucleatum, a member of “Orange complex,” is a common member of the oral microbiota in both periodontal health and disease and acts was a bridging species to metabolically connect early bacterial colonizers and late bacterial colonizers (i.e., potential pathogen “red complex” species) in the plaque maturation process. Furthermore, Fusobacterium nucleatum abundance levels were significantly higher in unhealthy teeth (gingivitis scores > 0.5) as compared to healthy teeth (gingivitis scores <0.05), as shown in Figure 3.

[0098] Fusobacterium nucleatum also plays a role in halitosis, dental pulp infection, and oral cancer. In addition, Fusobacterium nucleatum facilitates attachment of “red complex” bacterial species Porphyromonas gingivalis by activating human gingival fibroblast NADPH oxidase isoforms (NOXI and NOX2). The formation of microbial complex by these two species is believed to initiate the pathogenesis of periodontal disease. Interestingly, the abundance levels of Porphyromonas gingivalis in the subgingival plaque of dogs fed Test Food 2 showed a nonsignificant decreasing trend line as compared to dogs fed the other foods, as shown in Figure 4. Porphyromonas gingivalis abundance levels also showed significant reduction in healthy teeth compared to unhealthy teeth. Figure 4. Both Fusobacterium nucleatum and Porphyromonas gingivalis abundance levels were significantly higher in unhealthy teeth (based on gingivitis scores 0.5) as compared to healthy teeth (gingivitis scores <0.5), although a considerable number of teeth showed higher plaque scores, ranging from 4 to 8, as shown in Figure 5. This suggests that the presence of key microbial species is involved in initiating gingivitis and progression to periodontal disease, more so than the plaque build up itself. Porphyromonas gingivalis is considered a keystone pathogen and disturbs host-commensal homeostasis, eventually interfering with a host’s innate immunity to periodontal disease. Porphyromonas gingivalis prevalence in high in dogs (88%) and cats (96%) than other potential periodontal disease pathogens, such as Porphyromonas gulae (dogs 39%, cats 70%) and Tannerella forsythia (dogs 4%, cats 2%).

[0099] Fusobacterium nucleatum showed a significant positive relationship (R square 0.206, P value < 0.001) with the tooth gingivitis score, as shown in Figure 6, although no significant relationship with tooth plaque or tartar score was shown. Similarly, Fusobacterium nucleatum showed a non-significant positive relationship with whole mouth gingivitis score, but showed a non-significant inverse relationship with whole mouth plaque and tartai' scores, as shown in Figure 7. However, Porphyromonas gingivalis showed a significant positive relationship with tooth gingivitis score (R square 0.167, p value < 0.001), but not tooth plaque and tartar scores, as shown in Figure 8. Likewise, as shown in Figure 9, Porphyromonas gingivalis showed a non-significant positive relationship with whole mouth plaque, tartar, and gingivitis scores.

[0100] The foregoing findings support the conclusion that Test Food 2, containing D-ribose as an ingredient, improved oral health by significantly reducing whole mouth plaque score and modulating subgingival microbiome composition by specifically decreasing the abundance levels of key microbial species, Fusobacterium nucleatum and Porphyromonas gingivalis, as compared to the comparative foods that did not contain D-ribose.

Claims

CLAIMS What Is Claimed Is:

1. A method of treating, preventing, or alleviating periodontal disease of a companion animal, the method comprising administering to a companion animal in need thereof a composition comprising an effective amount of D-ribose.

2. The method according to according to claim 1, wherein the D-ribose is present in the composition in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the composition.

3. The method according to claim 1 or 2, wherein the periodontal disease of the companion animal is treated or alleviated by reducing the amount of at least one of tartar or plaque on the teeth of the companion animal as compared to before the composition was administered to the companion animal.

4. The method according to any one of the preceding claims, wherein the method reduces at least one of Fusobacterium nucleatum or Porphyromonas gingivalis present on the teeth of the companion animal as compared to before the composition was administered to the companion animal.

5. The method according to any one of the preceding claims, wherein the composition is a pet food composition in a form selected from a dry kibble, a wet loaf, a dental chew, or a treat.

6. The method according to claim 5, wherein the pet food composition is in the form of a dry kibble.

7. The method according to claim 6, wherein the D-ribose is in a coating enrobing the dry kibble.

8. The method according to any one of the preceding claims, wherein the composition further comprises at least one mechanical component for cleaning teeth.

9. The method according to claim 8, wherein the at least one mechanical component for cleaning teeth comprises a transverse, fibrous striated matrix.

10. The method according to any one of the preceding claims, wherein the companion animal is a dog.

11. The method according to any one of the preceding claims, wherein the composition is administered for 1 or more days, preferably 5 or more days, preferably 7 or more days, preferably 10 or more days, preferably 14 or more days, preferably 30 or more days, or preferably 42 or more days.

12. A pet food composition for treating, preventing, or alleviating periodontal disease of a companion animal, the pet food composition comprising an effective amount of D-ribose, wherein the pet food composition is in the form of a kibble comprising a coating comprising the D-ribose.

13. The pet food composition according to claim 12, wherein the D-ribose is present in the pet food composition in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the pet food composition.

14. The pet food composition according to claim 12 or 13, wherein the pet food composition is free of any additional sugars.

15. The pet food composition according to any one of claims 12-14, wherein the coating further comprises at least one palatant.

16. A method for reducing the accumulation of tartar comprising administering to a companion animal a pet food composition according to any one of claims 12-15.

17. A method for reducing the accumulation of plaque comprising administering to a companion animal a pet food composition according to any one of claims 12-15.

18. A method for reducing an amount of Fusobacterium nucleatum and/or Porphyromonas gingivalis in an oral cavity comprising administering to a companion animal a pet food composition according to any one of claims 12-15.

19. A dentifrice composition for treating, preventing, or alleviating periodontal disease of a companion animal, the dentifrice composition comprising an effective amount of D-ribose.

20. The dentifrice composition according to claim 19, wherein the D-ribose is present in the dentifrice composition in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the dentifrice composition.

21. The dentifrice composition according to claim 19 or 20, wherein the dentifrice composition is free of any additional sugars.

22. A method of making a pet food composition for treating, preventing, or alleviating the symptoms of periodontal disease, the method comprising:

(a) mixing wet and dry ingredients to form a dough;

(b) extruding the dough to form an extruded kibble;

(c) drying the extruded kibble; and

(d) enrobing the dried kibble with a topical liquid and/or dry ingredients, wherein D-ribose is applied to the kibble at step (a) and/or step (d), in an amount effective to treat, prevent, or alleviate the symptoms of periodontal disease in a companion animal who consumes the pet food composition.

23. The method according to claim 22, wherein the D-ribose is applied to the kibble at step (d).

24. The method according to claim 22 or 23, wherein the D-ribose is applied in an amount ranging from about 1 wt% to about 5 wt%, preferably from about 2 wt% to about 4 wt%, or about 2 wt%, by weight based on the total weight of the pet food composition.