CN114828643A

CN114828643A - Compositions having specific insoluble fiber to soluble fiber ratios for the treatment of, for example, anxiety

Info

Publication number: CN114828643A
Application number: CN201980103000.5A
Authority: CN
Inventors: 伊登·伊弗雷姆; 丹尼斯·朱厄尔
Original assignee: Hills Pet Nutrition Inc
Current assignee: Hills Pet Nutrition Inc
Priority date: 2019-12-19
Filing date: 2019-12-19
Publication date: 2022-07-29
Also published as: AU2019479288A1; CA3164486A1; JP2023507372A; EP4017276A1; AU2019479288B2; WO2021126221A1

Abstract

Compositions and methods for treating anxiety or stress in an animal are disclosed. Compositions and methods for reducing elevated levels of 4-EPS or preventing elevated levels of 4-EPS are disclosed. Compositions and methods for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in an animal microbiota are disclosed. The method comprises administering to the animal an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio. The composition comprises an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

Description

Compositions having specific insoluble fiber to soluble fiber ratios for the treatment of, for example, anxiety

Background

Microbial toxin 4-ethylphenyl sulfate (4-EPS) is a metabolite produced by intestinal microorganisms. Among other microbial metabolites, 4-EPS enters the systemic circulation. In canines in particular, increased levels of 4-EPS in the blood are associated with stress, anxiety, brain injury and other behavioral problems. Reduction of 4-EPS levels has been shown to alleviate symptoms of stress and anxiety.

Canine anxiety (anxiety) is a response to fear and agitation, or when a threat or fear situation is predicted by dogs. Some individual dogs experience a disproportionate degree of anxiety. Anxiety may progress to anxiety disorders and may lead to behavioral and other problems. Some dogs experience extensive anxiety in which case fear responses may manifest themselves in a variety of situations where a "normal" pet is unlikely to respond. Anxiety may manifest as one of a variety of anxiety disorders, such as generalized anxiety disorder, hyperstimulation anxiety, separation anxiety, claustrophobia, noise phobia, and the like.

The disease-treating factors may include genetic components, prenatal and neonatal stressors, maternal segregation, lack of social interaction, unfamiliarity, or previously unpleasant results when exposed to a stimulus (or similar). The most common causes are fear, segregation and aging. Anxiety associated with fear may be caused by noisy noise, strange people or animals, visual stimuli, new or strange environments and specific situations, etc. Age-related anxiety can affect older dogs and may be associated with Cognitive Dysfunction Syndrome (CDS). Separation anxiety is a specific anxiety resulting from the inability of pets to find comfort when separated from family members. About 14% of dogs have separation anxiety. Some separation anxiety may be the result of a twisted attachment that forms as the puppy grows and matures. In some cases, separation anxiety may occur in situations involving changes in family or daily living, while in other cases separation anxiety is associated with potential anxiety states and other behavioral problems such as phobias.

Anxiety can lead to disruptive behavior (particularly at exits or to the owner's property), producing painful sounds, soiling the house, drooling, pacing, restlessness, lack of stability, anorexia, and repetitive or compulsive behavior. In some cases, anxiety may lead to aggressive behavior.

Common symptoms of dog anxiety include assault, urination or defecation in the house, running water, a surge to speak, disruptive behavior, depression, excessive barking, pacing, sitting restlessness, and repetitive or compulsive behavior. Different dogs exhibit different symptoms and combinations of symptoms when they are anxious.

Canine stress is the reaction of dogs to altered or adapted requirements, usually manifested as stress or a sense of stress. Canine stress can lead to fear, agitation, hyperactivity, nervousness, oversensitivity or irritability. Negative stress, excessive stress and chronic stress can have adverse effects on behavior, health and overall well-being. Stress may cause disease, suppress the immune system, cause adverse behavior, and increase excitement, which increases the likelihood of aggressive behavior.

Causes of stress in dogs include sadness, conflict, excessive or insufficient stimulation, overcrowded conditions, environmental changes (timetables, humans, animals, increased noise); punitive training, insufficient social time, terrible events, ignorance, frustration, and uncertainty, among others.

Dogs may express that they are experiencing stress in different ways. Some of the signs that dogs are experiencing stress include dilated pupils, tight around eyes, whale eyes/half-moon eyes, yawning, licking lips/nose, wheezing, excessive salivation, smiling, fibrillation, bulging cheeks, exposed teeth, wrinkled nose, the ears being back-facing or standing upright. Other signs include physical strain, stretching, excessive hair loss, little or no movement, low body posture, shifting center of gravity, trembling/trembling, penile tenting, paw sweating, glabellar tightness, barking, howling, and boredom. When subjected to stress, dogs tend to change behavior. Common stress-induced behaviors typically include restlessness, insufficient or excessive sleep, nervousness/excessive alertness, irritability, excessive self-grooming, disruptive behavior, loss of appetite, paranoia/compulsive behavior, inability to concentrate, hyperactivity, increased urination and defecation, and vomiting and diarrhea, among others.

There is a need for methods and compositions for reducing elevated4-EPS levels in canines. There is a need for methods and compositions for treating elevated levels of anxiety or reducing the severity of anxiety in canines. There is a need for methods and compositions for treating elevated canine stress levels or reducing the severity thereof.

Disclosure of Invention

The present disclosure provides methods for treating anxiety or stress in an animal. The method comprises administering to the animal an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides methods for reducing elevated levels of 4-EPS in animals having elevated levels of 4-EPS. The method comprises administering to the animal an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides methods for preventing an increase in 4-EPS levels in an animal. The method comprises administering to an animal at risk of elevated4-EPS levels an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides methods for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in an animal microbiota. The method comprises administering to the animal an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides compositions for treating anxiety or stress in an animal. The composition comprises an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides compositions for reducing elevated levels of 4-EPS in animals having elevated levels of 4-EPS. The composition comprises an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides compositions for preventing elevated levels of 4-EPS in an animal. The composition comprises an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

The present disclosure provides compositions for promoting the growth of beneficial microorganisms and inhibiting the growth of non-beneficial microorganisms in an animal microbiota. The composition comprises an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

Drawings

Figure 1 shows data from the experiment described in example 1, where 4-EPS levels were measured in dogs after feeding a previous feed, control or test food composition. Relative blood levels of log 4-EPS after each 30 day period are shown for previous feeds, control/test, elution (previous feeds) and post-crossover treatment (control/test). The results show that the previous feeds caused significantly higher levels of 4-EPS (P < 0.0001) compared to the treatment diet (control/test).

Detailed Description

The following description of the preferred embodiment(s) is merely exemplary in nature and is in no way intended to limit the invention, its application, or uses.

As used herein and in the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

As used herein, the term "companion animal" includes any non-human animal suitable for being kept as a pet by humans, including, but not limited to, dogs, cats, rabbits, and rodents. Some particular embodiments are formulations and methods for treating dogs and/or cats. In one particular aspect, formulations and methods for treating dogs are provided.

The term "dog" includes those dogs that are companion animals, such as domestic dogs (Canis familiaris), working dogs, and the like. The term dog is synonymous with the term canine.

The term "cats" includes those cats that are companion animals referred to as domestic cats (domestic cat) or house cats (house cat) or domestic cats (Felis domestic). The term cat is synonymous with the term feline.

The terms "high solubility fiber" and "soluble fiber" are used interchangeably.

The terms "low solubility fiber" and "insoluble fiber" are used interchangeably.

The terms n-3 fatty acid and omega-3 fatty acid are used interchangeably.

The present disclosure provides methods for treating anxiety and stress in animals, particularly companion animals such as canines or felines. The method comprises administering to the animal an effective amount of an n-3 fatty acid, an antioxidant, and a combination of insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio. The composition comprises an effective amount of n-3 fatty acid, an antioxidant, and insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio. In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, and in some embodiments 0.65-0.85% of the daily nutritional intake, and in some embodiments 0.70-0.80% of the daily nutritional intake, and in some embodiments 0.72-0.79% of the daily nutritional intake. In some embodiments, the effective amount of the antioxidant comprises a combination of vitamin C and vitamin E. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin C is at a daily nutrient intake level of greater than 400ppm, and in some embodiments at a daily nutrient intake level of greater than 450ppm, and in some embodiments at a daily nutrient intake level of greater than 475ppm, and in some embodiments at a daily nutrient intake level of greater than 480ppm, and in some embodiments at a daily nutrient intake level of greater than 490ppm, and in some embodiments at a daily nutrient intake level of greater than 500ppm, and in some embodiments at a daily nutrient intake level of greater than 550 ppm. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1000IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1200IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1300IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1400IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1500 IUK. In some embodiments, the combination of insoluble fiber and soluble fiber is provided in an amount equal to 4.0% or more of the daily nutritional intake, in some embodiments equal to 4.5% or more of the daily nutritional intake, in some embodiments equal to 4.6% or more of the daily nutritional intake, in some embodiments equal to 4.7% or more of the daily nutritional intake, in some embodiments equal to 4.8% or more of the daily nutritional intake, in some embodiments equal to 4.9% or more of the daily nutritional intake, in some embodiments equal to 5.0% or more of the daily nutritional intake; provided in a ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) in a range between 2.0 and 3.0 in some embodiments, and between 2.1 and 2.9 in some embodiments, and between 2.2 and 2.8 in some embodiments, and between 2.3 and 2.7 in some embodiments, and between 2.4 and 2.6 in some embodiments, and between 2.4 and 2.5 in some embodiments.

"daily nutrient intake" and "total daily nutrient intake" refer to the daily intake of dry matter. That is, the weight of water is not included in the calculation of the amount of nutrients consumed per day. To the extent that the food and food ingredients contain water/moisture, dry matter means all matter in the sample other than water, including protein, fiber, fat, minerals, etc. Dry matter weight is the total weight minus the weight of any water. Daily dry matter intake is calculated as the total daily nutrient intake excluding all water. For example, an amount of an ingredient equal to a certain percentage of daily nutritional intake refers to the amount of the ingredient in dry matter (also excluding all water) relative to the total amount of dry matter (i.e., excluding all water) consumed on a day. The skilled artisan will readily recognize and appreciate the amounts and percentages of nutrients expressed as dry matter, dry matter weight and dry matter percentage. Since foods, whether wet, moist or dry, generally contain a certain amount of water, the water content of such foods is not included in the calculation of daily dry matter intake. To calculate the total daily nutrient intake, i.e. the daily dry matter intake, water was excluded. To calculate the percentage of one ingredient on a dry matter basis to total daily intake, water is removed from the total intake to give total daily dry matter intake, and the percentage of the ingredient is based on the amount of the ingredient present as dry matter.

The composition useful in the method may be a pet food composition, for example a dog food composition. Alternatively, the n-3 fatty acid, antioxidant, and insoluble and soluble fiber may be administered in the form of a supplement, snack, or toy, or not incorporated into the food provided to the animal for daily nutritional intake.

In some preferred embodiments, the animal is a canine and the method comprises administering to the canine an effective amount of n-3 fatty acid, antioxidant, and insoluble and soluble fiber. An effective amount of n-3 fatty acids administered to the canines is 0.6-0.9% and in some embodiments 0.65-0.85% and in some embodiments 0.70-0.80% and in some embodiments 0.72-0.79% of the daily nutritional intake.

The effective amount of antioxidant comprises a combination of vitamin C and vitamin E, and in some embodiments of the combination: an effective amount of vitamin C on a daily nutritional intake basis is at a level of greater than 400ppm, in some embodiments at a level of greater than 450ppm, in some embodiments at a level of greater than 475ppm, in some embodiments at a level of greater than 480ppm, in some embodiments at a level of greater than 490ppm, in some embodiments at a level of greater than 500ppm, and in some embodiments at a level of greater than 550 ppm; and the effective amount of vitamin E is at a level of greater than 1000IUK, in some embodiments greater than 1200IUK, in some embodiments greater than 1300IUK, in some embodiments greater than 1400IUK, and in some embodiments greater than 1500IUK on a daily nutritional intake. The combination of insoluble fiber and soluble fiber is provided in an effective amount equal to 4.0% or more, in some embodiments equal to 4.5% or more, in some embodiments equal to 4.6% or more, in some embodiments equal to 4.7% or more, in some embodiments equal to 4.8% or more, in some embodiments equal to 4.9% or more, in some embodiments equal to 5.0% or more by daily nutritional intake; and is provided in a ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) ranging between 2.0 and 3.0 in some embodiments, between 2.1 and 2.9 in some embodiments, between 2.2 and 2.8 in some embodiments, between 2.3 and 2.7 in some embodiments, between 2.4 and 2.6 in some embodiments, and between 2.4 and 2.5 in some embodiments. The composition is preferably a dog food composition comprising a daily effective amount of n-3 fatty acids, an antioxidant (e.g., a combination of vitamin C and vitamin E), and a combination of soluble and insoluble fibers.

The present disclosure provides compositions and methods for treating anxiety or stress in animals, particularly companion animals such as felines and canines. The compositions and methods are useful for treating symptoms of anxiety or stress in such animals in need thereof. The compositions and methods are useful for treating symptoms of anxiety or stress in such animals with elevated levels of 4-EPS. The compositions and methods are useful for reducing elevated levels of 4-EPS in animals (e.g., companion animals, particularly canines) having elevated levels of 4-EPS. In some embodiments, compositions and methods for treating canine anxiety or canine stress in canines. The present disclosure provides compositions and methods for promoting the growth of desirable beneficial microorganisms in a population of gut microorganisms and inhibiting the growth of undesirable unhealthy microorganisms in a population of gut microorganisms.

As used herein, the term "treating" refers to eliminating, reducing the severity of, or preventing one or more symptoms.

As used herein, the term "anxiety" refers to anxiety, anxiety disorders, and symptoms of anxiety and anxiety disorders.

As used herein, the term "stress" refers to stress, stress disorders, and symptoms of stress and stress disorders.

As used herein, the term "treatment" with reference to anxiety refers to therapeutic and/or prophylactic activity. In canines with symptoms of anxiety, treatment of the canine anxiety refers to elimination of symptoms, suppression or reduction of progression of symptoms, reduction of severity of symptoms, and prevention of symptoms. Treatment that initially eliminates, arrests, reduces the progression of, or reduces the severity of symptoms may continue, and continued treatment may further eliminate, arrests, reduce the progression of, or reduce the severity of symptoms, and/or prevent the recurrence or progression of symptoms, or reduce the severity of further progression of symptoms. In some embodiments, the canine may be identified as having anxiety symptoms prior to treating the canine for anxiety. In some embodiments, anxiety in canines can be treated without identifying symptoms of anxiety prior to treatment. In some embodiments, the canine can be identified as being predisposed to suffering from or developing anxiety prior to treatment for anxiety. In some embodiments, the canine can be identified as having an elevated level of 4-EPS prior to treatment for anxiety.

As used herein, the term "treatment" in reference to stress and stress disorders refers to therapeutic and/or prophylactic activities. In canines with symptoms of stress or stress disorder, treatment of canine stress refers to elimination of symptoms, suppression or reduction of progression of symptoms, reduction of severity of symptoms, and prevention of symptoms. Treatment that initially eliminates, arrests, reduces the progression of, or reduces the severity of symptoms may continue, and continued treatment may further eliminate, arrests, reduce the progression of, or reduce the severity of symptoms, and/or prevent the recurrence or progression of symptoms, or reduce the severity of further progression of symptoms. In some embodiments, the canine can be identified as having symptoms of stress or stress disorder prior to treating the canine for stress. In some embodiments, the stress or stress disorder in canines can be treated without identifying symptoms of anxiety prior to treatment. In some embodiments, the canine can be identified as being predisposed to or developing a stress or stress disorder prior to treatment of the stress or stress disorder. In some embodiments, the canine can be identified as having an elevated level of 4-EPS prior to treating the stress or stress disorder.

As used herein, reference to the term "treatment" in reference to promoting the growth of beneficial microorganisms and inhibiting the growth of detrimental microorganisms refers to therapeutic and/or prophylactic activity. In canines having reduced levels of beneficial microorganisms and increased levels of harmful microorganisms, the treatment is used to suppress the levels of beneficial and harmful microorganisms or to promote the growth of beneficial and inhibit the growth of harmful microorganisms. Prior to initiation of treatment, canines were identified as being prone to inhibit the growth of beneficial microorganisms and to promote the growth of harmful microorganisms. Treatment that promotes the growth of beneficial microorganisms and inhibits the growth of harmful microorganisms initially in animals with elevated levels of beneficial microorganisms and reduced levels of beneficial microorganisms can increase the levels of beneficial microorganisms and decrease the levels of harmful microorganisms to achieve a healthier balance, and then continue treatment to maintain the levels. In some embodiments, the canines can be identified as having an elevated level of harmful microorganisms and a reduced level of beneficial microorganisms prior to treatment of canine stress. In some embodiments, canines can be treated without identifying an increase in the level of harmful microorganisms and a decrease in the level of beneficial microorganisms in the animal.

As used herein, the terms "treatment of elevated4-EPS (treated 4-EPS)", "treatment of elevated4-EPS (treated for elevated 4-EPS)" and "treatment of elevated4-EPS (treated 4-EPS)" refer to therapeutic and/or prophylactic activities that reduce the level of 4-EPS. In canines with elevated4-EPS levels, "treatment of elevated4-EPS," "treatment for elevated4-EPS," and "treating elevated 4-EPS" refer to decreasing elevated4-EPS levels. Treatment may reduce elevated levels of 4-EPS to normal non-elevated levels or reduced elevated levels of 4-EPS. After reducing the elevated4-EPS levels, the treatment can prevent elevated4-EPS levels or reduce the severity of further elevated4-EPS levels. In canines that do not have an elevated level of 4-EPS, "treatment of elevated4-EPS," "treatment for elevated4-EPS," and "treating elevated 4-EPS" refer to suppressing or reducing the level of 4-EPS, and preventing an elevated level of 4-EPS or reducing the severity of an elevated level of 4-EPS. In some embodiments, the canine can be identified as having elevated4-EPS by measuring the level of 4-EPS prior to treatment of 4-EPS. In some embodiments, the elevated4-EPS of the canine can be treated without measuring the level of 4-EPS prior to treatment. In some embodiments, the canine may be identified as susceptible to elevated4-EPS prior to treatment of the 4-EPS. Canines identified as susceptible to elevated4-EPS may have elevated4-EPS when treated, in which case the treatment is therapeutic, or may not have elevated4-EPS, in which case the treatment is prophylactic, or may be treated without an established level of 4-EPS. In some embodiments, the canine may be identified as susceptible to elevated4-EPS prior to initiating treatment with or without measuring 4-EPS levels.

As used herein, "an effective … amount," "an effective amount," and similar terms refer to an amount of n-3 fatty acids and antioxidants effective, when delivered in combination with an effective insoluble fiber to soluble fiber ratio, to achieve a particular biological result, i.e., treating elevated levels of 4-EPS, anxiety, stress, and levels of beneficial and detrimental microorganisms in the microbiota. In particular embodiments, administration of a composition comprising an effective amount of n-3 fatty acid and an antioxidant in combination with an effective insoluble fiber to soluble fiber ratio will be for a time sufficient to effect treatment. In particular embodiments, the methods comprise administering and consuming a composition comprising an effective amount of n-3 fatty acid and a combination of an antioxidant and an effective insoluble fiber to soluble fiber ratio for a period of time sufficient to result in effective treatment and maintenance. An effective amount can be based on several factors, including the desired weight, age, sex, activity level of the dog, metabolizable energy of the composition, and frequency of feeding the composition, e.g., once, twice, or three times daily, as well as other compositions fed to the dog. In some embodiments, an effective amount refers to the amount of n-3 fatty acids and antioxidants combined with an effective insoluble fiber to soluble fiber ratio administered based on total daily nutritional intake. In some embodiments, an effective amount refers to a pet food comprising n-3 fatty acids and antioxidants in combination with an effective insoluble fiber to soluble fiber ratio on a dry matter basis of total daily nutritional intake. That is, on a dry matter basis, a food amount suitable to meet all daily nutritional and energy requirements of the canine subject contains an effective amount of n-3 fatty acids and antioxidants in combination with an effective insoluble fiber to soluble fiber ratio.

As used herein, "effective insoluble fiber to soluble fiber ratio" and similar terms refer to the ratio of insoluble fiber to soluble fiber in a daily diet effective, when delivered in combination with an effective amount of n-3 fatty acids and antioxidants, to achieve a particular biological result, i.e., treating elevated levels of 4-EPS, anxiety, stress, and levels of beneficial and detrimental microorganisms in the microbiota. An effective ratio can be based on several factors, including the desired weight, age, sex, activity level of the dog, metabolizable energy of the composition, and frequency of feeding the composition, e.g., once, twice, or three times daily, as well as other compositions fed to the dog. The effective ratio may be expressed as a number calculated by dividing the amount of insoluble fiber by the amount of soluble fiber (i.e., the amount of insoluble fiber/the amount of soluble fiber).

In particular embodiments, administration of a composition comprising an effective amount of n-3 fatty acid and an antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio will be for a time sufficient to effect treatment. In particular embodiments, the methods comprise administering and consuming a composition comprising an effective amount of n-3 fatty acid and antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio for a period of time sufficient to result in effective treatment and maintenance.

In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, and in some embodiments 0.65-0.85% of the daily nutritional intake, and in some embodiments 0.70-0.80% of the daily nutritional intake, and in some embodiments 0.72-0.79% of the daily nutritional intake.

In some embodiments, the effective amount of the antioxidant comprises a combination of vitamin C and vitamin E. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin C is at a daily nutrient intake level of greater than 400ppm, and in some embodiments at a daily nutrient intake level of greater than 450ppm, and in some embodiments at a daily nutrient intake level of greater than 475ppm, and in some embodiments at a daily nutrient intake level of greater than 480ppm, and in some embodiments at a daily nutrient intake level of greater than 490ppm, and in some embodiments at a daily nutrient intake level of greater than 500ppm, and in some embodiments at a daily nutrient intake level of greater than 550 ppm. In some embodiments, in the combination of vitamin C and vitamin E, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1000IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1200IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1300IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1400IUK, and in some embodiments, the effective amount of vitamin E is at a daily nutrient intake level of greater than 1500 IUK.

In some embodiments, the combination of insoluble fiber and soluble fiber is provided in an amount equal to 4.0% or more of the daily nutritional intake, in some embodiments equal to 4.5% or more of the daily nutritional intake, in some embodiments equal to 4.6% or more of the daily nutritional intake, in some embodiments equal to 4.7% or more of the daily nutritional intake, in some embodiments equal to 4.8% or more of the daily nutritional intake, in some embodiments equal to 4.9% or more of the daily nutritional intake, in some embodiments equal to 5.0% or more of the daily nutritional intake; provided in a ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) in a range between 2.0 and 3.0 in some embodiments, and between 2.1 and 2.9 in some embodiments, and between 2.2 and 2.8 in some embodiments, and between 2.3 and 2.7 in some embodiments, and between 2.4 and 2.6 in some embodiments, and between 2.4 and 2.5 in some embodiments.

In some preferred embodiments, the animal is a canine, and the method comprises administering to the canine an effective amount of a combination of n-3 fatty acid, antioxidants (e.g., vitamin C and vitamin E), and an effective ratio of insoluble fiber and soluble fiber. The combination may be administered in the form of a pet food composition, such as a dog food composition, or in the form of a supplement, treat, or toy, or not incorporated into the food provided to the animal for daily nutritional intake. In some embodiments, the effective amount of n-3 fatty acids is 0.6-0.9% of the daily nutritional intake, and in some embodiments 0.65-0.85% of the daily nutritional intake, and in some embodiments 0.70-0.80% of the daily nutritional intake, and in some embodiments 0.72-0.79% of the daily nutritional intake.

In some embodiments, a "food," "food composition," or "pet food composition" may be a nutritionally complete diet for the animal, e.g., a dog, to which it is fed.

As used herein, "ingredient" refers to any component of the composition.

The term "nutrient" refers to a substance that provides nutrition. In some cases, an ingredient may comprise more than one "nutrient," e.g., a composition may comprise corn containing important nutrients, including both protein and carbohydrates.

The food composition may be provided to the animal in the form of a pet food, such as, but not limited to, a pet. Pet owners have access to a variety of commonly known types of pet foods. Pet food options include, but are not limited to, wet pet food, semi-moist pet food, dry pet food, and pet treats. Wet pet foods typically have a moisture content of greater than about 65%. Semi-moist pet foods typically have a moisture content of between about 20% and about 65%, and may include humectants, potassium sorbate, and other ingredients to prevent microbial growth (bacteria and mold). Dry pet foods, such as but not limited to food kibbles, typically have a moisture content of less than about 15%. Pet treats may typically be semi-moist chewable treats; any number of forms of dried snacks, chewable bones, or baked, extruded or compression molded snacks; a confectionery snack; or other types of snacks known to those skilled in the art.

As used herein, the term "coarse abrasive particles" or "food coarse abrasive particles" refers to granular, pellet-like components of animal feed (e.g., dog and cat feed). In some embodiments, the food coarse abrasive particles have a moisture or water content of less than 15% by weight. The texture of the food coarse grit can vary from hard to soft. The internal structure of the food coarse abrasive particles can vary from expanded to densified. The food coarse abrasive particles may be formed by an extrusion process or a baking process. In a non-limiting example, the food coarse abrasive particles can have a uniform internal structure or a varying internal structure. For example, the food coarse abrasive particles can include a core and a coating to form coated coarse abrasive particles. It should be understood that when the term "coarse abrasive particle" or "food coarse abrasive particle" is used, it can refer to either an uncoated coarse abrasive particle or a coated coarse abrasive particle.

As used herein, the term "extrusion" refers to a process of feeding a pre-treated and/or pre-prepared mixture of ingredients through an extruder. In some extrusion embodiments, the food kibble is formed by an extrusion process, wherein a kibble dough (comprising a mixture of wet and dry ingredients) can be extruded under heat and pressure to form the food kibble. Any type of extruder may be used, examples of which include, but are not limited to, single screw extruders and twin screw extruders. Lists of sources, ingredients, and components are listed as described below such that combinations and mixtures thereof are also contemplated and are within the scope herein.

As contemplated herein, compositions are intended to encompass, but not be limited to, nutritionally complete and balanced animal food compositions. A "nutritionally complete diet" is a diet that includes sufficient nutrients for maintaining the normal health of healthy dogs on the diet. For example, nutritionally complete and balanced pet food compositions for canines are familiar to those skilled in the art. For example, substances suitable for nutritionally complete and balanced animal Feed compositions (e.g., nutrients and ingredients) and their recommended amounts can be found in official publications such as the American Association of Feed Control Officials (AAFCO), atlanta, georgia, (2012).

It is contemplated that when the dog is fed a diet comprising an effective amount of n-3 fatty acid and antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio, the preferred method comprises feeding the dog a diet comprising an effective amount of n-3 fatty acid and antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio. In other embodiments, feeding a dog a diet comprising an effective amount of n-3 fatty acids and antioxidants in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio can be accomplished by administering the n-3 fatty acids, antioxidants, and insoluble fiber to the dog in a supplement or snack format. Whether delivered as a pet food composition, as a separate supplement, or as a treat, providing a dog with an effective amount of n-3 fatty acid and antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio by any means is considered feeding the dog a diet comprising an effective amount of n-3 fatty acid and antioxidant in combination with an effective ratio of insoluble fiber and soluble fiber.

As used herein, the term "supplement" includes, but is not limited to, a feed used with another feed to improve the nutritional balance or performance of the animal's total diet. Supplements include, but are not limited to, compositions that are fed undiluted as a supplement to other feeds; (ii) freely select the provided composition along with other portions of the animal ration provided separately; or a composition that is diluted and mixed with an animal's regular feed to produce a complete feed. For example, the AAFCO guidelines contain discussions related to supplements in the official publications of the American Association of Feed Control Officials (AAFCO), atlanta, georgia, (2012). The supplement may be in various forms including, for example, powders, liquids, syrups, pills, encapsulated compositions, and the like.

The diet can comprise an effective amount of n-3 fatty acids and antioxidants in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio to reduce elevated4-EPS levels in an animal, such as a feline or canine. A diet comprising an effective amount of n-3 fatty acid and an antioxidant in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio can be used to treat anxiety in canines. A diet comprising an effective amount of n-3 fatty acids and antioxidants in combination with insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio can be used to treat stress in canines. A diet comprising an effective amount of n-3 fatty acids and antioxidants in combination with insoluble fibers and soluble fibers in an effective insoluble fiber to soluble fiber ratio can be used to promote the growth of beneficial microorganisms and inhibit the growth of detrimental microorganisms in an animal microbiota, particularly a microbiota of the gastrointestinal tract of an animal, and particularly an animal that is a feline or canine.

Compositions and formulations

The use of the methods outlined above has identified a combination of effective amounts of n-3 fatty acid and antioxidant with an effective ratio of insoluble and soluble fiber that provides significant benefit to animals, especially dogs and cats, identified as being susceptible to elevated4-EPS levels and therefore an increased risk of developing anxiety, an increased risk of developing anxiety stress, and an increased risk of inhibiting the growth of beneficial and promoting the growth of detrimental microorganisms in canine microbiota, especially intestinal microbiota. In some embodiments, the combination of an effective amount of n-3 fatty acid and antioxidant with an effective ratio of insoluble fiber and soluble fiber is a component that has been combined with other ingredients to provide a nutritionally complete diet. In some embodiments, the food product is a nutritionally complete diet for an adult companion animal. In a particular aspect, the food product is a nutritionally complete diet formulated for an adult companion canine.

In some embodiments, the compositions include a food composition suitable for consumption by a companion animal, particularly dogs, comprising an effective amount of n-3 fatty acids and antioxidants in combination with an effective ratio of insoluble fiber and soluble fiber, and protein and/or fat and/or carbohydrate. In some embodiments, for example, a nutritionally complete and balanced dog food composition may comprise, in addition to n-3 fatty acids, antioxidants, insoluble fiber, and soluble fiber: 4 to 90 wt.%, 4 to 75 wt.%, 5 to 75 wt.%, 10 to 60 wt.% of protein or 15 to 50 wt.% of protein, on a dry matter basis, based on the total weight of the composition; 0 to 90 wt%, 2 to 80 wt%, 5 to 75 wt%, and 10 to 50 wt% carbohydrate, on a dry matter basis, based on the total weight of the composition; and 2 to 60 wt.%, 5 to 50 wt.%, and 10 to 35 wt.% fat on a dry matter basis, based on the total weight of the composition. In some embodiments, for example, a nutritionally complete and balanced dog food composition may contain from 0 to 15% by weight or from 2% to 8% by weight of other vitamins and minerals, antioxidants, and other nutrients, such as amino acids that support the nutritional needs of an animal, in addition to n-3 fatty acids, antioxidants, insoluble fibers, and soluble fibers.

The composition comprises at least one n-3 fatty acid, also known as an omega-3 fatty acid. Omega-3 fatty acids, also known as n-3 fatty acids, are a recognized group of polyunsaturated fatty carboxylic acids, also known as polyunsaturated fatty acids (PUFAs). Omega-3 fatty acids are characterized by the presence of a double bond between carbon atoms t3 and 4, as measured from the end of the molecule that does not contain a carboxyl group, i.e., three atoms from the terminal methyl group in its chemical structure. They have conventional or branched long chain polyalkenyl groups, having from about 8 to about 24 carbon atoms, preferably from about 10 to about 22 carbon atoms, including the carbon atoms of the carboxyl group.

Examples of omega-3 fatty acids include, but are not limited to, alpha-linoleic acid (ALA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and stearidonic acid. In some embodiments, the composition comprises one of ALA, DHA, or EPA. In some embodiments, the composition comprises at least two of ALA, DHA, or EPA. In some embodiments, the composition comprises all three of ALA, DHA, and EPA. Omega-3 fatty acids are generally exemplified by EPA and DHA and are generally considered to be the most important and significant of the long chain omega-3 fatty acids. Generally, these long chain fatty acids are present in relatively low, almost trace amounts or are not present at all in typical pet food compositions. The fatty acid composition of foods consumed by companion pets, such as dogs and cats, directly affects the biological levels of fatty acids present in their blood. Natural products with a relatively high content of omega-3 unsaturated fatty acids, such as EPA and DHA, may be derived from marine oils, such as salmon, anchovies, sardines and herrings. Such natural oils may be concentrated to an even higher percentage of omega-3 fatty acids.

Derivatives of omega-3 fatty acids may also be employed. Many types of derivatives are well known to those skilled in the art. Examples of suitable derivatives are esters, such as branched or unbranched and/or saturated or unsaturated C-C cycloalkyl esters, especially C-C alkyl esters. Their systemic potential has been recognized in the art, for example, in U.S. patent nos. 5,776,913 and 6,015,798. As used in this application and in the claims, "omega-3 fatty acids" include derivatives thereof.

With respect to the amount of omega-3 fatty acids or mixtures of omega-3 fatty acids, in some embodiments the amount should be administered is 0.6 to 0.9 wt% daily nutritional intake on a dry matter basis, and in some embodiments 0.65 to 0.85% daily nutritional intake on a dry matter basis, and in some embodiments 0.70 to 0.80% daily nutritional intake on a dry matter basis, and in some embodiments 0.72 to 0.79% daily nutritional intake on a dry matter basis, as measured by the amount of the daily dietary composition. In some embodiments, EPA and DHA are preferred omega-3 fatty acids.

In some embodiments, the method comprises administering an amount of total fatty acids equal to a daily nutritional intake of about 10-15% by weight on a dry matter basis, and in some embodiments equal to a daily nutritional intake of 11-14% by weight on a dry matter basis, and in some embodiments equal to a daily nutritional intake of 12-13% by weight on a dry matter basis, and in some embodiments equal to a daily nutritional intake of 12.1-12.6% by weight on a dry matter basis, and in some embodiments equal to a daily nutritional intake of 12.2-12.4% by weight on a dry matter basis. The percentage of n-3 fatty acids relative to total fatty acids may be 4.0 to 8.5%, and in some embodiments 4.5 to 8.0%, in some embodiments 5.0 to 7.5%, in some embodiments 5.5 to 7.0%, and in some embodiments 5.5 to 6.5%.

The composition further comprises at least one antioxidant. Antioxidants are well known in the art. Examples of antioxidants include, but are not limited to, vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin, carnitine, and beta-carotene. In some embodiments, the composition comprises at least one of vitamin C, vitamin E (tocopherol and/or tocotrienol), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least two of vitamin C, vitamin E (tocopherol and/or tocotrienol), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least three of vitamin C, vitamin E (tocopherol and/or tocotrienol), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least four of vitamin C, vitamin E (tocopherol and/or tocotrienol), glutathione, lipoic acid, melatonin, or beta-carotene. In some embodiments, the composition comprises at least five or more of vitamin C, vitamin E (tocopherols and/or tocotrienols), glutathione, lipoic acid, melatonin and/or beta-carotene. In some embodiments, the composition comprises vitamin C and vitamin E. Vitamin C can be administered in such diets in the form of ascorbic acid and its various derivatives, such as calcium phosphate salts, cholesterol salts, 2-monophosphate, and the like, which will exert vitamin C-like activity upon ingestion by the pet. They may be in any form, for example liquid, semi-solid, solid and heat stable forms.

Vitamin C may be provided at a daily nutrient intake level of greater than 400ppm, in some embodiments at a daily nutrient intake level of greater than 450ppm, in some embodiments at a daily nutrient intake level of greater than 475ppm, in some embodiments at a daily nutrient intake level of greater than 480ppm, in some embodiments at a daily nutrient intake level of greater than 490ppm, and in some embodiments at a daily nutrient intake level of greater than 500ppm, and in some embodiments at a daily nutrient intake level of greater than 550 ppm. Vitamin E may be provided at a daily nutrient intake level of greater than 1000IUK, in some embodiments at a daily nutrient intake level of greater than 1200IUK, and in some embodiments at a daily nutrient intake level of greater than 1300IUK, and in some embodiments at a daily nutrient intake level of greater than 1400IUK, and in some embodiments at a daily nutrient intake level of greater than 1500 IUK.

Dietary fiber refers to a component of a plant that resists digestion by animal digestive enzymes. The dietary fiber content of the composition can be determined by any number of methods known to those skilled in the art, such as those published by OMA. Dietary fiber includes soluble fiber and insoluble fiber.

Soluble fiber is not readily digested and absorbed in the small intestine, but is fully or partially fermented in the large intestine. Examples of sources of soluble fiber include beet pulp, guar gum, chicory root, psyllium, pectin, blueberry, cranberry, pumpkin, apple, oat, legumes, citrus, barley, and pea. The insoluble fiber may be provided from any of a variety of sources, including cellulose, whole wheat products, wheat oats, corn bran, flaxseed, grapes, celery, green beans, broccoli, potato skins, fruit skins, vegetable skins, peanut shells, and soy fiber. Crude fiber includes the cell walls and indigestible components contained in the cell contents of plants such as grains, such as the hulls of grains such as rice, corn, and beans. The crude fiber content of the composition can be determined by any number of methods known to those skilled in the art, preferably OMA method 991.43/32.1.17 (1994).

The combination of insoluble fibre and soluble fibre may be provided in an amount equivalent to a daily nutrient intake of 4.0 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 4.5 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 4.6 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 4.7 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 4.8 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 4.9 wt% or more on a dry matter basis, in some embodiments a daily nutrient intake of 5.0 wt% or more on a dry matter basis; provided in a ratio of insoluble fiber to soluble fiber (amount of insoluble fiber/amount of soluble fiber) in a range between 2.0 and 3.0 in some embodiments, and between 2.1 and 2.9 in some embodiments, and between 2.2 and 2.8 in some embodiments, and between 2.3 and 2.7 in some embodiments, and between 2.4 and 2.6 in some embodiments, and between 2.4 and 2.5 in some embodiments.

In some embodiments, the composition used in the method comprises crude fiber in an amount equivalent to 0.6-1.4 wt% or more of daily nutrient intake on a dry matter basis, equivalent to 0.7-1.3 wt% or more of daily nutrient intake on a dry matter basis, equivalent to 0.8-1.2 wt% or more of daily nutrient intake on a dry matter basis, equivalent to 0.9-1.1 wt% or more of daily nutrient intake on a dry matter basis, equivalent to about 1.0 wt% or more of daily nutrient intake on a dry matter basis.

Sources of protein, carbohydrate, fat, vitamins, minerals, balancing agents, and the like suitable for inclusion in the compositions, and in particular in the food products administered in the methods provided herein, can be selected from those conventional materials known to those of ordinary skill in the art.

Proteins useful as ingredients of food compositions can comprise proteins from animal sources, such as animal proteins, including mammalian, avian proteins, reptiles, amphibians, fish, invertebrate proteins, and combinations thereof; for example from any of the following: cattle, sheep, pigs, goats, deer, rabbits, horses, kangaroos, their milk, curd, whey or blood, as well as internal tissues and organs, such as smooth muscle, striated muscle, liver, kidney, intestine or heart; chickens, including internal tissues and organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart and chicken eggs, additional sources of avian protein encompass turkeys, geese, ducks, ostriches, quail, pigeons, their eggs, and internal tissues and organs such as smooth muscle, striated muscle, liver, kidney, intestine or heart; amphibian sources include frogs or salamanders, reptile protein sources include alligators, lizards, turtles and snakes; sources of fish protein include catfish, herring, salmon, tuna, bluefish, cod, halibut, trout, swordfish, and their eggs; and the source of invertebrate protein comprises lobster, crab, clam, mussel or oyster, and combinations thereof, meat protein isolates, whey protein isolates, egg protein, mixtures thereof, and the like; and vegetable sources such as corn gluten meal, wheat gluten, mixtures thereof, and the like.

In some embodiments, carbohydrates useful as ingredients of a food composition may include, but are not limited to, one or more of the following: corn, whole yellow corn, sorghum, wheat, barley, rice, millet, brewers' rice, oat groats and polysaccharides (e.g., starch and dextrin) and sugars that are metabolized to energy upon hydrolysis (e.g., sucrose, lactose, maltose, glucose, and fructose). Examples of additional carbohydrate sources suitable for inclusion in the compositions disclosed herein include fruits and vegetables.

Fats that can be used as ingredients of the food composition can be from any source, such as, but not limited to, poultry fat, tallow, lard, selected white fats, soybean oil, corn oil, rapeseed oil, sunflower oil, mixtures thereof, and the like. The fat may be incorporated completely within the food composition, deposited on the exterior of the food composition, or a mixture of both processes.

In some embodiments, the composition further comprises an effective amount of one or more substances selected from the group consisting of: glucosamine, chondroitin sulfate, methylsulfonylmethane ("MSM"), creatine, antioxidants, Perna canaliculata (Perna canaliculus), omega-3 fatty acids, omega-6 fatty acids, and mixtures thereof.

In some embodiments, the food composition further comprises one or more amino acids such as, but not limited to, arginine, histidine, isoleucine, leucine, lysine, methionine (including DL-methionine and L-methionine), phenylalanine, threonine, tryptophan, valine, taurine, carnitine, alanine, aspartic acid, cystine, glutamic acid, glutamine, glycine, proline, serine, tyrosine, and hydroxyproline.

In some embodiments, the food composition further comprises one or more fatty acids other than the omega-3 fatty acids described above, such as, but not limited to, lauric acid, myristic acid, palmitic acid, palmitoleic acid, heptadecanoic acid, heptadecenoic acid, stearic acid, oleic acid, linoleic acid, gadoleic acid, arachidonic acid, behenic acid, erucic acid, behenic acid.

In some embodiments, the food composition further comprises one or more macronutrients such as, but not limited to, moisture, protein, fat, crude fiber, ash, dietary fiber, soluble fiber, insoluble fiber, raffinose, and stachyose.

In some embodiments, the food composition further comprises one or more micronutrients, such as, but not limited to, beta-carotene, alpha-lipoic acid, glucosamine, chondroitin sulfate, lycopene, lutein, and quercetin.

In some embodiments, the food composition further comprises one or more minerals such as, but not limited to, calcium, phosphorus, potassium, sodium, chloride, iron, copper, manganese, zinc, iodine, selenium, cobalt, sulfur, fluorine, chromium, boron, and oxalates.

In some embodiments, the food composition further comprises a stabilizing substance, such as a substance that tends to increase the shelf life of the composition. Potentially suitable examples of such materials include, for example, preservatives, antioxidants, synergists and sequestrants, encapsulating gases, stabilizers, emulsifiers, thickeners, gelling agents, and humectants. Examples of emulsifiers and/or thickeners include, for example, gelatin, cellulose ethers, starch esters, starch ethers, and modified starches.

In some embodiments, the food composition further comprises additives for coloring, palatability, and nutritional purposes, including, for example, colorants; iron oxide, sodium chloride, potassium citrate, potassium chloride and other edible salts; a vitamin; a mineral; and a flavoring agent. The amount of such additives in the composition is generally up to 5% (dry weight of the composition).

Preparation of the composition

Compositions comprising n-3 fatty acids, antioxidants, insoluble fiber, and soluble fiber as outlined above can be prepared as food products suitable for consumption by dogs. These food products may have any consistency or moisture content; that is, the composition may be a moist, semi-moist, or dry food product. "moist" food products are typically food products having a moisture content of 60% to 90% or more. A "dried" food product is typically a food product having a moisture content of 3% to 11% and is typically manufactured in the form of small chunks or coarse abrasive particles. "semi-moist" food products typically have a moisture content of 25% to 35%. The food product may also include components having more than one consistency, such as soft, chewy meat-like particles or chunks, and coarse abrasive particles having an outer cereal component or coating and an inner "cream" component.

In some embodiments, food products of n-3 fatty acids, antioxidants, insoluble fibers, and soluble fibers as outlined above can be prepared in a canned or wet form using conventional food preparation methods known to one of ordinary skill in the art. Typically, the ground animal proteinaceous tissue is mixed with other ingredients, such as cereal grains, suitable carbohydrate sources, fats, oils and balance 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. The mixture is heated using any suitable means, such as direct steam injection or using a vessel equipped with a heat exchanger. After all ingredients of the formulation were added, the mixture was heated to a temperature of 50 to 212 ° f. While temperatures outside this range may be used, it may be commercially impractical without the use of other processing aids. When heated to the appropriate temperature, the material is typically in the form of a viscous liquid, which is dispensed into the can. The lid was closed and the container hermetically sealed. The sealed can is then placed into conventional equipment designed to sterilize the contents. Sterilization is typically accomplished by heating to a temperature in excess of 230 ℃ for an appropriate time depending on the temperature used, the nature of the composition and related factors. The compositions and food products of the invention may also be added to or combined with food compositions before, during or after preparation.

In some embodiments, the food product may be prepared in a dry form using conventional methods known to one of ordinary skill in the art. Typically, dry ingredients (including dried animal protein, vegetable protein, grain, etc.) are ground and mixed together. Liquid or wet ingredients (including fats, oils, animal proteins, water, etc.) are then added and combined with the dry material. The specific formulations, order of addition, combinations, and methods and apparatus for combining the various ingredients may be selected from those known in the art. For example, in certain embodiments, the resulting mixture is processed into coarse abrasive particles or similar dry pieces, which are formed using an extrusion process, wherein a mixture of dry and wet ingredients is subjected to a high pressure and high temperature mechanical process, forced through a small opening or orifice, and cut into coarse abrasive particles, for example, with a rotating knife. The resulting kibble can be dried and optionally coated with one or more surface coatings comprising, for example, flavors, fats, oils, powdered ingredients, and the like. Coarse abrasive particles may also be prepared from dough by baking rather than extrusion, wherein the dough is placed into a mold followed by a dry heat treatment.

In preparing the compositions, any of the ingredients can generally be incorporated into the compositions during processing of the formulation, for example, during and/or after mixing of the other components of the composition. The distribution of these components in the composition can be accomplished in a conventional manner. In certain embodiments, the ground animal and/or poultry protein tissue is mixed with other ingredients, including nutritional balancing agents, inorganic salts, and may also include cellulose, beet pulp, bulking agents, and the like, as well as sufficient water for processing.

In some embodiments, the composition is formulated to be more easily chewed. In particular embodiments, the compositions and food products are formulated to address specific nutritional differences between animal species and breeds, as well as one or more attributes of the animal. For example, canine foods, for example, are typically formulated based on life stage, age, size, weight, body composition, and breed.

In another embodiment, a snack comprising effective amounts of n-3 fatty acids, antioxidants, insoluble fibers and soluble fibers as outlined above may be prepared, for example, by an extrusion or baking process similar to that described below for dry foods, to provide an edible product. Treats include, for example, compositions that are administered to an animal to entice the animal to eat during non-meal times. Treats may be nutritional, wherein the composition comprises one or more nutrients, and may, for example, have a composition as described above for food. Non-nutritive snacks encompass any other non-toxic snacks. The composition may be coated onto a snack, incorporated into a snack, or both.

In another embodiment, an animal toy is provided that is a chewable or edible toy. Such toys are generally prepared by coating any existing toy with an effective amount of an n-3 fatty acid, an antioxidant, insoluble fiber, and soluble fiber as outlined above. Thus, toys include, for example, chewable toys. Toys for dogs contemplated include, for example, artificial bones. In certain embodiments, the compositions of the present invention may form a coating on the surface of a toy or on the surface of a component of a toy, or they may be partially or fully incorporated into a toy, or both. There are a number of suitable toys on the market today. See, for example, U.S. patent No. 5,339,771 (and references disclosed in U.S. patent No. 5,339,771). See also, for example, U.S. Pat. No. 5,419,283 (and the references disclosed in U.S. Pat. No. 5,419,283). It should be appreciated that the present invention encompasses both partially edible toys (e.g., toys comprising plastic components) and fully edible toys (e.g., rawhide and various artificial bones). It should further be appreciated that the present invention encompasses toys for use with companion animals, particularly cats or dogs.

All publications mentioned herein are incorporated by reference to describe and disclose the materials and methods reported in the publications and which can be used in connection with the invention.

Further areas of applicability of the present invention will become apparent from the detailed description provided hereinafter. It should be understood that the detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention.

Examples

Example 1

The microbial metabolite 4-ethylphenyl sulphate (4-EPS) is associated with stress and anxiety. The level of 4-EPS in the blood can be measured. Blood was collected for determination of plasma metabolomics profiles. The level of 4-EPS in plasma can be measured by a commercial laboratory (Metabolon, Durham, NC, USA). The extracted supernatant was separated and run on a gas and liquid chromatography mass spectrometer platform. The peak values of 4-EPS are known and the area under each peak can be normalized to known samples (see also: Evans, A.M. et al (2009), Integrated non-targeted ultra high performance liquid chromatography/electrospray ionization tandem Mass Spectrometry platform for identification and relative quantification of biological systems small molecule complement (Integrated, non-acquired ultra high Performance liquid chromatography/electrophoresis ionization for the identification and relative quantification of the biological systems), analytical chemistry (anal.chem..) 81, 6656-6667). Gas chromatography (for hydrophobic molecules) and liquid chromatography (for hydrophilic molecules) are used to identify and provide relative quantification of metabolites such as 4-EPS present in plasma samples. (see also: Ballet, C. et al (2018), New enzyme and Mass Spectrometry methods for the selective study of gut microbiota-derived metabolites (New enzyme and Mass Spectrometry methods for the selective uptake of gut microbiota-derived metabolites), chemistry (chem. Sci.)9, 6233-substituted antibodies 6239; Akiyama, Y et al (2012), Metabolic methods for elucidating the Effect of AST-120on 5/6-kidney-excised Rats by Capillary Electrophoresis and Mass Spectrometry (CE-MS) (A Metabolic application to Clarifying the Effect of AST-120on 5/6 New functionalized Rats by Capillary Electrophoresis) 4. the results of adsorption of urine Toxins with Mass Spectrometry results (CE-MS) 11, and the results of the oral toxicity of urine Toxins by adsorption of protein kinase K120 (US) 11. et al (for the selective study of gut microbiota-derived metabolites by the oral liquid chromatography methods of protein-induced metabolism method of (CE-MS) 120. the results of the oral metabolism of the metabolites of the gut microbiota by Capillary Electrophoresis and Mass Spectrometry (CE-MS) 11. the oral metabolism of the metabolites of the human origin of the metabolites of the urinary tract an oral sorbent AST-120by liquid chromatography/chromatography mass spectrometry), J.chromatogrAN _ SNhy B- -analytical techniques in biomedicine and Life sciences (J.chromatogr B analytical technique Biomed Life Sci)878: 2997-3002.

The study was completed for 40 dogs, each dog fed 3 different foods (previous feeds, controls and tests) at different times. As shown in table 1, the previous feeds contained low soluble fiber, high insoluble fiber, low n-3 fatty acids and antioxidants, and the control and test foods each contained high soluble fiber, low insoluble fiber, high n-3 fatty acids and high antioxidants.

TABLE 1 diet analysis results (%)

The insoluble fiber to soluble fiber ratios of the previous feeds, control and test foods were 3.88%, 2.49% and 2.39%, respectively. The percentage of total n-3 fatty acids of the previous feed was 3.2. The percent of total n-3 fatty acids in the control and test foods were 5.87 and 6.42, respectively.

During the first 30 days (days 0-30), all dogs were fed the previous feed. After the initial pre-feeding period, the control group (20 dogs) received the control food for 30 days (days 31-60), while the test group (20 dogs) received the test food for 30 days (days 31-60). The animals then underwent a 30 day washout period (days 61-90) during which they were fed the previous feed. After the 30 day washout period with the previous feed, a 30 day crossover (days 91-120) was performed to feed the groups with food they did not receive before (control or test). That is, after completion of the elution period, dogs that consumed the control food during days 31-60 consumed the test food on days 91-120, while dogs that consumed the test food during days 31-60 consumed the control food on days 91-120.

Samples were collected at the end of every 30 days to compare 4-EPS levels in blood with changes in microbial composition in feces. Dogs had the highest 4-EPS level (P < 0.0001) when fed the previous diet compared to the test or control diet (fig. 1). There was a significant difference in the abundance of certain microbial OTUs after previous feeding of the food compared to the test or control food (table 2). (OUT refers to the operational taxonomic unit OTU is used to classify bacteria based on sequence similarity.) these include unclassified bacteria in the bacterial genus Odobacterium (Odorobacter), Parabacteroides (Parabacteroidide), Blautia (Blautia) and Pseudomonas family (Pseudomonas). All bacterial genera decreased after consumption of the previous feeds, except that the bacterial genera in the pseudomonas family were higher after consumption of the previous feeds by dogs (table 2). The genera Clinobacterium, Parabacteroides, Brucella are inversely related to the circulating levels of 4-EPS, whereas unclassified bacteria in the family Pseudomonas are positively related to the blood levels of 4-EPS (Table 3). There was no significant difference in microbial composition after consumption of the test and control foods.

In summary, the combination of insoluble and soluble fiber, n-3 fatty acids and antioxidants in the test and control foods (i.e. the foods contain a ratio of insoluble fiber to soluble fiber between 2.4 and 2.5; levels of vitamin C and vitamin E above 400ppm and above 1000IUK, respectively; and a percentage of total n-3 fatty acids between 5.5 and 6.5) reduced the level of the microbial stress-related metabolite 4-EPS. This unique combination of fiber, antioxidant and n-3 fatty acid reduces 4-EPS by altering gut microbial composition.

Identifying a canine microbial signature associated with a 4-EPS change. Fiber fermenting microorganisms such as Parabacteroides, Blauettia and Oesobacter are inversely associated with an increase in 4-EPS levels. Unclassified bacterial genera in the family of the pseudomonadaceae are correlated well with circulating levels of 4-EPS and increase after consumption of previous feeds.

Foods containing highly soluble fiber, n-3 fatty acids and antioxidants as described previously reduced 4-EPS by increasing parabacteroides, blautia and osmidium and reducing bacterial genera in the pseudomonas family. Table 2 shows the difference in relative abundance of bacterial OTUs after consumption of the previous feed, control food and test food.

TABLE 2

Example 2

The following composition is based on total nutrients provided daily.

In some embodiments, the amount of n-3 fatty acids is equal to 0.6-0.9% of the daily nutritional intake, the amount of vitamin C is greater than 400ppm of the daily nutritional intake, the amount of vitamin E is greater than 1000IUK of the daily nutritional intake, the amount of insoluble fiber and soluble fiber is equal to about 4.0-6.0% and the ratio (insoluble fiber/soluble fiber) is in the range between 2.0 and 3.0, on a dry matter basis, based on the total weight of the composition. In some embodiments, the composition comprises, on a dry matter basis, based on the total weight of the composition: chicken in an amount of 5% to 25%; egg protein in an amount of 4% to 15%; corn gluten meal in an amount of 6% to 20%; vegetables in an amount of 0.5% to 2%; fruit in an amount of 0.5% to 2%; and a carbohydrate selected from the group consisting of millet, brewer's rice, oat groats and combinations thereof in an amount of 5% to 50% on a dry matter basis based on the total weight of the composition.

In some embodiments, the amount of n-3 fatty acids, on a dry matter basis, based on the total weight of the composition, is in some embodiments from 0.65 to 0.85% of daily nutritional intake, in some embodiments from 0.70 to 0.80% of daily nutritional intake, and in some embodiments from 0.72 to 0.79% of daily nutritional intake.

In some embodiments, the amount of vitamin C is equal to 450ppm, in some embodiments equal to 475ppm, in some embodiments equal to 480ppm, in some embodiments equal to 485ppm, in some embodiments equal to 490ppm, in some embodiments equal to 500ppm, in some embodiments equal to 550ppm or more, based on the total weight of the composition on a dry matter basis; and the amount of vitamin C is equal to 1000IUK, in some embodiments equal to 1200IUK, in some embodiments equal to 1300IUK, in some embodiments equal to 1400IUK, in some embodiments equal to 1500IUK or more.

In some embodiments, the amount of insoluble fiber and soluble fiber is equal to 4.0% on a dry matter basis based on the total weight of the composition, in some embodiments equal to 4.1%, in some embodiments equal to 4.2%, in some embodiments equal to 4.3%, in some embodiments equal to 4.4%, in some embodiments equal to 4.5%, in some embodiments equal to 4.6%, in some embodiments equal to 4.7%, in some embodiments equal to 4.8%, in some embodiments equal to 4.9%, in some embodiments equal to 5.0% or more, and a ratio of insoluble fiber to soluble fiber (i.e., amount of insoluble fiber/amount of soluble fiber) of 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, and in some embodiments in the range of 2.4 to 2.6, and in some embodiments in the range of 2.4 to 2.5.

In certain embodiments, the composition may comprise chicken in an amount of 5%, 7.5%, 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, or 25% on a dry matter basis based on the total weight of the composition. In certain embodiments, the composition may comprise egg protein in an amount of 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% or 15% on a dry matter basis, based on the total weight of the composition. In certain embodiments, the composition may comprise corn gluten meal in an amount of 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% based on the total weight of the composition on a dry matter basis. In certain embodiments, the composition may comprise the vegetable source in an amount of 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or 2.0% based on the total weight of the composition on a dry matter basis. In certain embodiments, the composition may comprise the fruit source in an amount of 0.0%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, or 1.9%, or 2.0% based on the total weight of the composition on a dry matter basis. In certain embodiments, the composition may comprise carbohydrates selected from the group consisting of millet, brewer's rice, oat groats, and combinations thereof in an amount of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% on a dry matter basis based on the total weight of the composition. In particular aspects of these embodiments, the compositions of the invention may comprise a carbohydrate source dry weight within a range defined by any two of these values as endpoints.

Example 3

Table 3 describes certain embodiments having composition ratios (% by dry weight of the component compositions).

TABLE 3

A daily diet comprising effective amounts of n-3 fatty acids, vitamin C, vitamin E, insoluble fiber, and soluble fiber can provide a benefit to a dog identified as having stress. In some embodiments, a method comprises: identifying the dog as having or suspected of having stress, a stress disorder, or exhibiting symptoms of stress or a stress disorder; and feeding the dog a daily diet comprising effective amounts of n-3 fatty acids, vitamin C, vitamin E, insoluble fiber, and soluble fiber.

Example 4

Table 4 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 4

Example 5

Table 5 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 5

Example 6

Table 6 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 6

Composition (I)	w/w%, exceptfor the marked item
		n-3 fatty acid	0.72-0.79
Vitamin C	400ppm*
		Vitamin E	1000IUK
Insoluble fiber and soluble fiber	4.74-4.89
		Insoluble fiber/soluble fiber ratio	2.39-2.49
Rice, brewed product	23.00-25.00
		Pea, protein concentrate	9.00-10.00
Chicken, dry 10% ash	7.00-9.00
		Chicken, grinding and fresh	6.00-7.00
Sorghum, whole body	6.36
		Chicken powder	6.14
Pork fat, selected white oil	1.00
		Flax, seeds, whole body	3.00
Egg, drying, and granulating	5.50
		Hickory nut fiber	4.80
G03 buckwheat grains without husk	4.00
		Oat, hulled grain	4.00
Captex 355 medium chain triglycerides	3.00
		Chicken meat, liver, digestive, optimizing agent LDPE H	2.00
Oat, fiber	1.50
		Beet, pulp, grinding, and refining	1.50
Lactic acid, food grade	1.50
		Fish oil, TG, 18/12, NP	1.20
Flav Gen#1+CWG	1.00
		Potassium chloride	0.30
Carnitine, 1, 10%	0.27
		Natural flavoring agent, pork, liver, digestive, D' T	0.25
Choline chloride, liquid, 70%	0.18
		Sensimune 75 (yeast cell wall)	0.15
Vitamin E, oil, 29%	0.14
		Taurine	0.10
Sodium chloride, iodide	0.10
		Lysine, 1, hydrochloride	0.10
Minerals, premix, 2305	0.04
		Oat fiber, fruit, vegetable blend	0.04
Dicalcium phosphate	0.04

Example 7

Table 7 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 7

Composition (I)	w/w%, exceptfor the marked item
		n-3 fatty acid	0.72-0.79
Vitamin C	400ppm*
		Vitamin E	1000IUK
Insoluble fiber and soluble fiber	4.74-4.89
		Insoluble fiber/soluble fiber ratio	2.39-2.49
Rice, brewed product	—
		Chicken powder	6.00-7.00
Pea, protein concentrate	7.00-8.00
		Cellulose, coarse	3.00-4.00
Chicken, dry 10% ash	5.00-6.00
		Crushing barley, pearls, etc	18.00-20.00
Chicken meat, grinding and fresh	7.00-8.00
		Flax, seeds, whole body	2.00
Coconut oil with quality guarantee	4.00
		Chicken meat, liver, digestive, optimizing agent LDPE H	3.00
Lactic acid	1.50
		Methionine, dl	0.64
Potassium chloride	0.50
		Sodium chloride, iodide	0.60
Fish oil, TG, 18/12, NP	0.50
		Calcium carbonate	0.30
Choline chloride, liquid, 70%	0.25
		Carnitine, 1, 10%	0.30
Vitamin E, oil, 29%	0.17
		Minerals, premix, 2305	0.08
Taurine	0.06
		Oat, hulled grain	10.00
Buckwheat husk-removed grain	6.92
		Pea, bran, flour	5.00
The concentration of the tomato, the slag,	5.00
		beet, pulp, grinding, and refining	3.00

Example 8

Table 8 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 8

Composition (A)	w/w%, exceptfor the marked item	w/w%, exceptfor the marked item
			n-3 fatty acid	0.6-0.9	0.6-0.9
Vitamin C	400 or more ppm	400 or more ppm
			Vitamin E	1000 or more IUK	1000 or more IUK
Insoluble fiber and soluble fiber	4.0-5.0	4.0-5.0
			Insoluble fiber/soluble fiber ratio	Ratio between 2.0 and 3.0	Ratio between 2.0 and 3.0
Corn starch	31.10	48.11
			Hydrolyzed chicken liver and muscle heart	37.00	32.00
Soybean oil, crude product, degumming	3.60	4.66
			Cellulose, granules	—	3.94
Chicken meat, liver, digestive, optimizing agent LDPE H	2.00	2.00
			Lactic acid, food grade	1.50	1.50
Calcium carbonate	1.22	1.22
			Dicalcium phosphate	1.22	1.22
Selection of white fat/phosphoric acid	1.25	1.00
			Flav Gen#1+CWG	1.25	0.75
Glyceryl monostearate	0.74	0.74
			Potassium chloride	0.69	0.69
Natural flavoring agent, pork, liver, digestive, D' T	0.75	0.50
			Sodium chloride, iodide	0.44	0.44
Choline chloride, liquid, 70%	0.38	0.38
			Methionine, dl	0.30	0.30
Sodium tripolyphosphate	0.15	0.15
			Vitamin premix	0.12	0.12
Minerals, premix, 2305	0.07	0.07
			Taurine	0.02	0.02
Grinding pecan shell	7.00	—
			Flaxseed, whole, brown	3.00	—
Beet, pulp, grinding, and refining	2.50	—
			Cranberry pomace	1.00	—

Example 9

Table 9 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

TABLE 9

Example 10

Table 10 describes the ingredients used in certain embodiments with composition proportions (% by weight of dry matter of the component compositions).

Watch 10

Except for the marked item

Claims

1. A method for treating anxiety or stress in an animal comprising administering to the animal an effective amount of n-3 fatty acid, an antioxidant, insoluble fiber and soluble fiber in an effective insoluble fiber to soluble fiber ratio.

2. The method of claim 1 wherein the animal is administered n-3 fatty acids equal to 0.6-0.9% of daily nutrient intake, vitamin C at a daily nutrient intake level of 400ppm or more, vitamin E at a daily nutrient intake level of 1000IUK, and insoluble fiber and soluble fiber at an insoluble fiber/soluble fiber ratio of between 2.0 and 3.0.

3. The method of claim 1, wherein the animal is administered n-3 fatty acids equal to 0.65-0.85% of daily nutritional intake.

4. The method of claim 1, wherein the animal is administered n-3 fatty acids equal to 0.70-0.75% of daily nutritional intake.

5. The method of claim 1, wherein the animal is administered n-3 fatty acids equal to 0.72-0.79% of daily nutritional intake.

6. The method of any one of claims 1-5 wherein the animal is administered vitamin C equal to 450ppm of daily nutritional intake.

7. The method according to any one of claims 1 to 5 wherein the animal is administered vitamin C equal to 475ppm of daily nutritional intake.

8. The method according to any one of claims 1 to 5 wherein the animal is administered vitamin C equal to 490ppm of daily nutritional intake.

9. The method of any one of claims 1-8 wherein the animal is administered vitamin E equivalent to a daily nutritional intake of 1100 IUK.

10. The method of any one of claims 1-8 wherein the animal is administered vitamin E equivalent to a daily nutritional intake of 1200 IUK.

11. The method of any one of claims 1-8 wherein the animal is administered vitamin E equal to a daily nutritional intake of 1400 IUK.

12. The method of any one of claims 1-11 wherein insoluble fiber and soluble fiber are administered to the animal at an insoluble fiber/soluble fiber ratio of between 2.2 and 2.7.

13. The method of any one of claims 1-11 wherein insoluble fiber and soluble fiber are administered to the animal at an insoluble fiber/soluble fiber ratio of between 2.3 and 2.6.

14. The method of any one of claims 1-11 wherein the animal is administered insoluble fiber and soluble fiber at a ratio of insoluble fiber/soluble fiber of between 2.4 and 2.5.

15. The method of any one of claims 1 to 14 wherein the animal is administered an amount of insoluble fiber and soluble fiber equal to 4.0-5.5% of daily nutritional intake.

16. The method of any one of claims 1 to 14 wherein the animal is administered an amount of insoluble fiber and soluble fiber equal to 4.5-5.0% of daily nutritional intake.

17. The method of any one of claims 1 to 14 wherein the animal is administered an amount of insoluble fiber and soluble fiber equal to 4.7-4.9% of daily nutritional intake.

18. The method of any one of claims 1-17, wherein the animal is a canine.

19. The method of claim 18 wherein the canine is identified as having an elevated level of 4-ethylphenylsulfate.

20. The method of claim 18, wherein the canine has been previously identified as having canine anxiety.

21. The method of claim 18 wherein the canine has been previously identified as having symptoms of canine stress.

22. A food composition for treating anxiety, stress or stress disorders in an animal comprising effective amounts of n-3 fatty acids, vitamin C, vitamin E, insoluble fiber and soluble fiber, wherein the effective amount of n-3 fatty acids is equal to 0.6-0.9% of daily nutritional intake, vitamin C is at a daily nutritional intake level of 400ppm or more, vitamin E is at a daily nutritional intake level of 1000IUK, and the insoluble fiber/soluble fiber ratio of insoluble fiber and soluble fiber is between 2.0 and 3.0.

23. The food composition of claim 22 wherein the effective amount of n-3 fatty acids is equal to 0.65-0.85% of daily nutritional intake, vitamin C is at a daily nutritional intake level of 450ppm or more, vitamin E is at a daily nutritional intake level of 1100IUK, and the insoluble fiber/soluble fiber ratio of insoluble fiber and soluble fiber is between 2.2 and 2.8.

24. The food composition of claim 22 wherein the effective amount of n-3 fatty acids is equal to 0.70-0.80% of daily nutritional intake, vitamin C is at a daily nutritional intake level of 475ppm or more, vitamin E is at a daily nutritional intake level of 1200IUK, and the insoluble fiber/soluble fiber ratio of insoluble fiber and soluble fiber is between 2.3 and 2.7.

25. The food composition of claim 22 wherein the effective amount of n-3 fatty acids is equal to a daily nutrient intake of 0.72-0.79%, vitamin C is at a daily nutrient intake level of 490ppm or more, vitamin E is at a daily nutrient intake level of 1400IUK, and the insoluble fiber/soluble fiber ratio of insoluble fiber and soluble fiber is between 2.4 and 2.5.

26. The food composition of any one of claims 22-25 wherein the amount of insoluble fiber and soluble fiber is equal to 4.0-5.5% of the daily nutritional intake.

27. The food composition of any one of claims 22-25 wherein the amount of insoluble fiber and soluble fiber is equal to 4.5-5.0% of the daily nutritional intake.

28. The food composition of any one of claims 22-25 wherein the amount of insoluble fiber and soluble fiber is equal to 4.7-4.9% of the daily nutritional intake.

29. The food composition of any one of claims 22-28 wherein the food composition is a canine food composition.