Compositions and methods using a combination of at least one fiber and at least one probiotic to improve microbiome resilience

Abstract

The composition comprises a combination of at least one fiber and at least one probiotic, and is formulated for administration to a subject, such that the combination of at least one fiber and at least one probiotic enhances the resilience of the subject's microbiome.Preferably, the subject is experiencing, will be experiencing, and / or has recently experienced a microbiome stressor, such as one or more of dietary stressor, antibiotics, other drugs, infection, strenuous exercise, stress, alcohol, travel, and combinations thereof; more preferably, at least a dietary stressor; most preferably, at least a high-fat diet, such as a Western-style high-fat diet or a ketogenic diet.The method can achieve at least one result: (i) prevention or attenuation of microbiota perturbation; (ii) recovery after perturbation; and (iii) normalization of one or more of stool frequency, intestinal transit, constipation, intestinal permeability, endotoxemia, or intestinal barrier function.

Description

[Technical field]

[0001] [Background technology]

[0001] The present disclosure relates generally to methods for improving microbiome resilience, and further to compositions useful in the methods, as well as methods of making such compositions.

[0002]

[0002] The human gut microbiome is an ecosystem of trillions of bacteria. Throughout life, the gut microbiome is subjected to one or more of the following stresses: unhealthy diet, antibiotics, other drugs, infections, strenuous exercise, or alcohol. The ability of the microbiome to resist these stresses, or to recover quickly and completely from perturbations, is "microbiome resilience" and likely contributes to maintaining health. A reduction in microbiome resilience can lead to dysbiosis, which has adverse health effects.

[0003] [Summary of the Invention]

[0003] There is increasing evidence that the gut microbiome plays an important role in health and disease. However, the resilience of the microbiota after high-fat dietary stress has not been addressed. The clinical study disclosed herein demonstrates that the intake of a combination of a fiber blend and a probiotic mixture improves microbiome resilience, intestinal transit, and intestinal barrier in subjects challenged with a high-fat and low-fiber diet. Therefore, the present disclosure generally relates to a novel improvement of microbiome resilience by the combination of a fiber blend and a probiotic mixture to improve gastrointestinal health.

[0004]

[0004] Benefits from improving this microbiota resilience include, for example, prevention or attenuation of microbiota perturbation; management of microbiota imbalance; recovery following perturbation; and normalization of one or more of stool frequency, intestinal transit, constipation, gut permeability, endotoxemia, or intestinal barrier function (e.g., to endotoxins).

[0005]

[0005] Additional features and advantages are described herein, and will be apparent from the drawings and detailed description that follow. [Brief description of the drawings]

[0006] [Figure 1] FIG. 1 is a schematic diagram outlining microbiota resilience as defined herein. [Diagram 2] FIG. 1 is a schematic diagram showing the clinical study design of the experimental examples disclosed herein. [Figure 3A] 1 is a table showing the textile formulations used in the experimental examples disclosed herein. [Figure 3B] 1 is a table showing the probiotic product formulations used in the experimental examples disclosed herein. [Figure 4] FIG. 1 is a graph showing the effect of interventions on the prevalence of microbiota members over time. [Diagram 5] FIG. 13 is a graph showing the effect of intervention and high fat dietary challenge on alpha diversity. [Figure 6] 1 is a graph showing the results of experimental examples disclosed herein, demonstrating that a high fat diet results in less disruption of the microbiota when nutritional intervention is performed. [Figure 7] 1 is a graph showing changes in the microbiota community structure. [Figure 8A] 1 is a graph showing the results for the Resistance Index obtained in the experimental examples disclosed herein, where Resistance=1 / dmax, where dmax is the maximum Aitchison distance during loading relative to baseline (day=0). [Figure 8B] 1 is a graph showing the results for the Resistance Index obtained in the experimental examples disclosed herein, where Resistance=1 / dmax, where dmax is the maximum Aitchison distance during loading relative to baseline (day=0). [Figure 8C] 1 is a table showing the results for the Resistance Index obtained in the experimental examples disclosed herein. Resistance=1 / dmax, where dmax is the maximum Aitchison distance during loading relative to baseline (day=0). [Figure 9A] 1 is a table showing the results for the Recovery Index obtained in the experimental examples disclosed herein. Recovery = time to reach minimum Aitchison distance after peak. Mean recovery is averaged per group and per classification level. [Figure 9B] 1 is a graph showing results for the recovery index at family level. [Figure 10] 1 is a graph showing the difference in metabolic composition relative to baseline. [Figure 11] 1 is a graph showing host effect results from experimental examples disclosed herein, demonstrating that nutritional intervention normalizes stool frequency during loading. [Figure 12A] 1 is a graph showing results of the host effects obtained in the experimental examples disclosed herein, demonstrating that the increase in antibodies against blood endotoxin levels induced by a high fat diet is prevented by nutritional intervention. [Figure 12B] 1 is a graph showing results of the host effects obtained in the experimental examples disclosed herein, demonstrating that the increase in antibodies against blood endotoxin levels induced by a high fat diet is prevented by nutritional intervention.

[0007] [Mode for carrying out the invention]

[0020] definition

[0021] Some definitions are provided below. However, definitions may be found in the "Embodiments" section below, and the heading "Definitions" above does not imply that such disclosure in the "Embodiments" section is not a definition.

[0008]

[0022] All percentages stated herein are by total weight of the composition unless otherwise indicated. As used herein, "about," "approximately," and "substantially" are understood to refer to numbers within a certain range of numerical values, for example, within the range of -10% to +10% of the referenced number, preferably within the range of -5% to +5% of the referenced number, more preferably within the range of -1% to +1% of the referenced number, and most preferably within the range of -0.1% to +0.1% of the referenced number. All numerical ranges herein should be understood to include all integers or fractions within the range. Furthermore, these numerical ranges should be interpreted as supporting claims directed to any number or subset of numbers within the range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges such as 1 to 8, 3 to 7, 1 to 9, 3.6 to 4.6, 3.5 to 9.9, etc.

[0009]

[0023] As used in this disclosure and the appended claims, the singular forms "a," "an," and "the" include plural references unless otherwise indicated. Thus, for example, a reference to "a vitamin" or "the vitamin" includes both embodiments having a single vitamin and embodiments having two or more vitamins.

[0010]

[0024] The terms "comprise", "comprises", and "comprising" should be interpreted as inclusive rather than exclusive. Similarly, the terms "include", "including", and "or" should all be interpreted as inclusive unless such interpretation is clearly prevented by the context. However, the compositions disclosed herein may not include elements not specifically disclosed herein. Thus, disclosure of an embodiment using the term "comprising" includes disclosure of an embodiment "consisting essentially of" the specified components, and an embodiment "consisting of" the specified components.

[0011]

[0025] The terms "at least one of" and "and / or" used in the context of "at least one of X or Y" and "X and / or Y", respectively, should be interpreted as "X", or "Y", or "X and Y". For example, "at least one of resistance or recovery" and "resistance and / or recovery" should be interpreted as "resistance", or "recovery", or "both resistance and recovery".

[0012]

[0026] As used herein, the terms "examples" and "such as," especially when followed by a list of terms, are merely exemplary and illustrative and should not be considered as exclusive or inclusive. As used herein, a condition "associated with" or "linked with" another condition means that the conditions occur simultaneously, preferably that the conditions are caused by the same underlying condition, and most preferably that one of the specified conditions is caused by the other specified condition.

[0013]

[0027] "Prevention" includes reducing the risk, incidence and / or severity of a condition or disorder. The terms "treatment" and "treating" include both prophylactic or preventative treatment (treatment that prevents and / or delays the onset of the pathological condition or disorder of interest) and curative, therapeutic or disease-modifying treatment, including, for example, therapeutic measures to cure, delay, reduce symptoms and / or halt the progression of a diagnosed pathological condition or disorder, as well as treatment of patients at risk of or suspected of having a disease, and patients who are unwell or diagnosed with a disease or medical condition. The terms "treatment" and "treating" do not necessarily mean that the subject is treated until fully cured. The terms "treatment" and "treating" also refer to maintaining and / or promoting the health of individuals who are not suffering from a disease but who may be susceptible to an unhealthy condition. The terms "treatment" and "treating" are also intended to include the synergism or otherwise potentiation of one or more primary preventative or therapeutic measures. By way of non-limiting example, treatment can be performed by the patient, a caregiver, a doctor, a nurse, or another medical professional.

[0014]

[0028] As used herein, a prophylactically or therapeutically "effective amount" is an amount that prevents a deficiency, treats a disease or medical condition in an individual, or, more generally, reduces symptoms, manages the progression of a disease, or provides a nutritional, physiological, or medical benefit to an individual. Relative terms such as "promote," "improve," "increase," and "enhance" refer to the resilience of a subject's microbiome following administration of a composition disclosed herein (including fiber and probiotics) compared to the resilience (i.e., resistance to and / or recovery from a challenge) of the subject's microbiome achieved by administration of an otherwise identically formulated composition but without the fiber and / or probiotics.

[0015]

[0029] As used herein, the terms "food," "food product," and "food composition" refer to a product or composition intended for oral ingestion by humans or other mammals and containing at least one nutrient for humans or other mammals.

[0016]

[0030] As used herein, "nutritional composition" and "nutritional product" include any number of food ingredients and possibly optional additional ingredients based on the functional needs of the product and in full compliance with all applicable regulations. Optional ingredients may include, but are not limited to, conventional food additives such as one or more acidulants, additional thickeners, pH adjusting buffers or pH adjusting agents, chelating agents, colorants, emulsifiers, excipients, flavorings, minerals, osmotic agents, pharma-ceutically acceptable carriers, preservatives, stabilizers, sugars, sweeteners, modifiers and / or vitamins. Optional ingredients may be added in any suitable amount.

[0017]

[0031] "Probiotic" means a microbial cell preparation or microbial cell component that has a beneficial effect on the health or well-being of the host. (Salminen S, Ouwehand A. Benno Y. et al., "Probiotics: how should they be defined", Trends Food Sci. Technol., 1999:10 107-10).

[0018]

[0032] As used herein, the term "unit dosage form" refers to a physically discrete unit suitable as a dosage unit for human and animal subjects, each unit containing a predetermined amount of a composition disclosed herein, in an amount sufficient to produce the desired effect, together with a pharma- ceutically acceptable diluent, carrier, or vehicle. The specifications for the unit dosage form depend on the particular compound used, the effect to be achieved, and the pharmacodynamics associated with each compound in the host.

[0019]

[0033] A "subject" or "individual" is a mammal, preferably a human.

[0020]

[0034] Embodiment

[0035] As shown in Figure 1, microbiome resilience is defined as the ability to resist or fully and rapidly recover from a stress or disturbance. Accordingly, one aspect of the present disclosure is a composition comprising a combination of at least one fiber and at least one probiotic, the combination formulated for administration to a subject such that the combination enhances the resilience of the subject's microbiome.

[0021]

[0036] Another aspect is a method of enhancing microbiome resilience in a subject (e.g., a subject in need of enhanced microbiome resilience), comprising administering to the subject (e.g., in a therapeutically or prophylactically effective amount) a composition comprising a combination of at least one fiber and at least one probiotic. In one embodiment, the subject is experiencing a microbiome stressor and / or has recently experienced a microbiome stressor (e.g., less than a year ago, preferably less than a month ago, more preferably less than a week ago, and most preferably less than a day ago).

[0022]

[0037] A related embodiment is a method of treating, preventing, reducing the incidence, and / or reducing the severity of a condition associated with a microbiome stressor in a subject experiencing a microbiome stressor, who has recently experienced a microbiome stressor (e.g., within the last month or week), and / or who will experience a microbiome stressor in the near future (e.g., within the next month or week), comprising administering to the subject a composition comprising a combination of at least one type of fiber and at least one type of probiotic (e.g., in a therapeutically or prophylactically effective amount).

[0023]

[0038] In a preferred embodiment, the stressor is a dietary stressor, such as a high-fat diet, for example, a Western diet or a ketogenic diet, or a low-carbohydrate diet.As used herein, a high-fat diet is a daily caloric intake in which more than 35% of the daily caloric intake is derived from dietary fat, for example, at least about 40% of the daily caloric intake is derived from dietary fat, at least about 45% of the daily caloric intake is derived from dietary fat, at least about 50% of the daily caloric intake is derived from dietary fat, at least about 55% of the daily caloric intake is derived from dietary fat, or at least about 60% of the daily caloric intake is derived from dietary fat.

[0024]

[0039] The Western diet is characterized by highly processed and refined foods; high sugar, salt and fat; protein from red meat; and low fiber. "Low fiber" is considered a diet having less than 15 grams of fiber per 2000 calories per day.

[0025]

[0040] As used herein, a low carbohydrate diet is one in which about 15% or less of the daily caloric intake comes from carbohydrates, for example, about 10% or less of the daily caloric intake comes from carbohydrates, or about 5% or less of the daily caloric intake comes from carbohydrates.

[0026]

[0041] In some embodiments, the subject has been consuming a high fat diet (e.g., a Western diet, or a ketogenic diet) or a low carbohydrate diet for at least one day (e.g., at least one week or at least one month) prior to the initial administration of the combination of at least one type of fiber and at least one type of probiotic, optionally followed by administration of the combination of at least one type of fiber and at least one type of probiotic (e.g., daily administration for a period of at least one week or at least one month).

[0027]

[0042] Additionally or alternatively, the stressor may include one or more of: antibiotics; other medications; infections; strenuous exercise; stress; alcohol; travel; parenteral nutrition; enteral nutrition; short bowel syndrome; intestinal inflammation; chemotherapy; colon cancer; diarrhea; proton pump inhibitors; a gluten-free diet; a diet free of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs); or combinations thereof.

[0028]

[0043] In some embodiments, the subject takes one of the compositions disclosed herein daily, for example, for at least one week prior to the stressor, or even for at least one month prior to the stressor.

[0029]

[0044] Yet another embodiment is a unit dosage form of a composition comprising a combination of at least one fiber and at least one probiotic, the unit dosage form comprising an amount of the combination (of the at least one fiber and the at least one probiotic) effective to enhance the resilience of the microbiome of a subject to which the unit dosage form is administered.

[0030]

[0045] Yet another aspect is a method of producing a composition for enhancing the resilience of the microbiome of a subject to which the composition is administered, comprising the step of adding at least one type of fiber to at least one type of probiotic and preferably at least one additional ingredient.

[0031]

[0046] Another aspect is a method of achieving at least one result selected from the group consisting of: (i) prevention or attenuation of microbiota perturbation; (ii) recovery following perturbation; and (iii) normalization of one or more of stool frequency, intestinal transit, constipation, intestinal permeability, endotoxemia, or intestinal barrier function, comprising enhancing microbiome resilience in a subject (e.g., a subject in need thereof) by administering to the subject (e.g., in an effective amount) a composition comprising a combination of at least one fiber and at least one probiotic.

[0032]

[0047] Yet another aspect is a method of improving gastrointestinal health, comprising enhancing microbiome resilience in a subject (e.g., a subject in need thereof) by administering to the subject (e.g., in an effective amount) a composition comprising a combination of at least one type of fiber and at least one type of probiotic.

[0033]

[0048] In embodiments disclosed herein, each of the at least one fiber is edible, i.e., all components of the fiber are safe and suitable for human and / or animal consumption. The at least one fiber comprises insoluble fiber and / or soluble fiber, preferably a blend of insoluble and soluble fiber. In some embodiments, the at least one fiber can be selected from the group consisting of xylooligosaccharides, flaxseed, partially hydrolyzed guar gum (PHGG), glucomannan, cellulose, prune powder, pectin such as apple skin pectin, and mixtures thereof. In some embodiments, the at least one fiber is at least two fibers, such as two, three, four, five, six, or seven fibers, and optionally more fibers. Optionally, one or more of Monk fruit powder, xylitol, or magnesium (e.g., magnesium citrate) can be included with the at least one fiber.

[0034]

[0049] In some embodiments, the at least one probiotic may be selected from the group consisting of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus rhamnosus, Bifidobacterium longum, Lactobacillus plantarum, Bifidobacterium bifidum, Lactobacillus gasseri, and mixtures thereof. In some particular embodiments, the at least one probiotic can be a strain selected from the group consisting of Lactobacillus acidophilus La-14, Bifidobacterium lactis Bl-04, Lactobacillus rhamnosus GG, Bifidobacterium longum BL-05, Lactobacillus plantarum Lp-115, Bifidobacterium bifidum Bb-06, Lactobacillus gasseri Lg-36, and mixtures thereof. In some embodiments, the at least one probiotic is at least two probiotic strains, for example, two, three, four, five, six, or seven probiotic strains, and optionally more probiotic strains.

[0035]

[0050] The at least one fiber may be administered to the individual in a total daily dose of about 5 g to 40 g, preferably about 15 g to 25 g. The at least one fiber may be administered in a composition comprising about 300 mg to 1000 mg of total fiber per gram of dry composition.

[0036]

[0051] At least one probiotic should be at least 1×10 3 cfu ~ 1 × 10 12 cfu (cfu = colony forming units), preferably 1 × 10 7 cfu ~ 1 × 10 11At least one probiotic may be administered to an individual as a daily dose of 1×10 cfu. 3 cfu ~ 1 × 10 12 The composition may be administered in a composition comprising cfu / g of dry composition. The at least one probiotic may be live, fragmented, or in the form of a fermentation product (e.g., supernatant) or metabolic product, or a mixture of any or all of these states.

[0037]

[0052] The combination of at least one fiber and at least one probiotic is preferably administered orally in a composition, such as a food composition.

[0038]

[0053] The subject to which the combination of at least one fiber and at least one probiotic is administered can be selected from the group consisting of a human infant, a human child, a human adolescent, a human adult, and a human geriatric.

[0039]

[0054] The combination of the at least one fiber and the at least one probiotic may be administered to an individual by at least one route selected from the group consisting of oral, topical, enteral, and parenteral. For example, the combination of the at least one fiber and the at least one probiotic may be administered in a composition selected from the group consisting of a complete nutrition product, a beverage, a dietary supplement, a meal replacement, a food additive, a supplement to a food product, a powder for dissolution, an enteral nutrition product, an infant formula, a capsule, and combinations thereof.

[0040]

[0055] Optionally, the combination of at least one fiber and at least one probiotic is administered in a composition further comprising at least one component selected from the group consisting of amino acids, proteins, nucleotides, fish oil, a non-marine source of omega-3 fatty acids, phytonutrients, antioxidants, and mixtures thereof.

[0041]

[0056] The composition may be a food product, an animal food product, or a pharmaceutical composition. For example, the product may be a nutritional composition, a nutraceutical, a beverage, a food additive, or a pharmaceutical. The food additive or pharmaceutical may be in the form of, for example, a tablet, capsule, lozenge, liquid, or powder in a sachet.

[0042]

[0057] In some embodiments, the at least one probiotic is administered simultaneously with the at least one fiber in a separate composition, e.g., in separate compositions administered to the same individual within 1 hour of each other, preferably within 30 minutes of each other, more preferably within 10 minutes of each other, and most preferably within 1 minute of each other.

[0043]

[0058] The composition comprising a combination of at least one type of fiber and at least one type of probiotic is preferably selected from the group consisting of: dairy powder based products; instant beverages; ready-to-drink formulations; nutritional powders; nutritional liquids; dairy based products, in particular yogurt or ice cream; cereal products; beverages; water; coffee; cappuccino; malt beverages; chocolate flavoured beverages; cooked products; soups; tablets; and / or syrups.

[0044]

[0059] The composition may optionally comprise any milk obtained from an animal or vegetable source, such as, for example, one or more of cow's milk, human milk, sheep's milk, goat's milk, horse's milk, camel's milk, rice milk, or soy milk. Additionally or alternatively, a milk-derived protein fraction or colostrum may be used.

[0045]

[0060] The compositions comprising a combination of at least one fiber and at least one probiotic may further contain protective hydrocolloids (gums, proteins, modified starches, etc.), binders, film formers, encapsulants / encapsulants, wall / shell materials, matrix compounds, coatings, emulsifiers, surfactants, solubilizers (oils, fats, waxes, lecithin, etc.), adsorbents, carriers, fillers, co-compounds, dispersants, wetting agents, processing aids (solvents), flow agents, flavoring agents, bulking agents, jellifying agents, gel forming agents, antioxidants, and antimicrobial agents.

[0046]

[0061] The composition comprising the combination of at least one fiber and at least one probiotic may also contain conventional pharmaceutical additives and adjuvants, excipients and diluents, including, but not limited to, water, gelatin from any source, vegetable gums, lignin sulfonates, talc, sugar, starch, gum arabic, vegetable oils, polyalkylene glycols, flavorings, preservatives, stabilizers, emulsifiers, buffers, lubricants, colorants, wetting agents, fillers, etc. Additionally, the composition may contain vitamins, minerals, trace elements and other micronutrients in accordance with recommendations of government agencies such as the USRDA, in addition to organic or inorganic carrier materials suitable for oral or enteral administration.

[0047]

[0062] The composition comprising a combination of at least one fiber and at least one probiotic may optionally contain one or more amino acids, a protein source, a carbohydrate source, and / or a lipid source, particularly in embodiments of the composition that are food products.

[0048]

[0063] Any suitable food-derived protein may be used, such as animal proteins (such as milk proteins, meat proteins, and egg proteins); vegetable proteins (such as soy proteins, wheat proteins, rice proteins, and pea proteins); mixtures of free amino acids; or combinations thereof. Dairy proteins such as casein and whey, and soy proteins are particularly preferred.

[0049]

[0064] The composition comprising at least one type of fiber and at least one type of probiotic can be administered to humans or animals, particularly companion animals, pets, or livestock. The composition has beneficial effects on all age groups. Preferably, the composition is formulated for administration to infants, juveniles, adults, or the elderly. In some embodiments, the composition can be administered to pregnant and lactating mothers to treat infants.

[0050]

[0065] The composition comprising the combination of at least one fiber and at least one probiotic can be administered at least 1 day per week, preferably at least 2 days per week, more preferably at least 3 or 4 days per week (e.g., every other day), most preferably at least 5 days per week, 6 days per week, or 7 days per week. The administration period may be at least 1 week, preferably at least 1 month, more preferably at least 2 months, most preferably at least 3 months, e.g., at least 4 months. In one embodiment, administration is at least daily, e.g., the subject may receive one or more administrations per day. In some embodiments, administration continues for the remainder of the individual's life. In other embodiments, administration is administered until there is no detectable symptom of the medical condition. In a specific embodiment, administration is administered until there is a detectable improvement in at least one symptom, and in further cases, administration is continued to maintain remission.

[0051]

[0066] [Example]

[0067] The following non-limiting examples generally illustrate the concepts underlying the embodiments disclosed herein.

[0052]

[0068] Figure 2 shows the design of a clinical study using a fiber product containing a diverse fiber blend to improve overall microbiome diversity and a probiotic product to replenish down-regulated bacteria, reduce inflammation, and improve the intestinal barrier. Figure 3A shows the fiber product formulation, and Figure 3B shows the probiotic product formulation.

[0053]

[0069] The results are shown in Figures 4 to 12. Specifically, Figure 4 shows the effect of the intervention on the abundance of microbiota-constituting bacteria over a period of time. The intervention increases the overall abundance of microbiota-constituting bacteria throughout the duration of the experiment. This increase in abundance highlights the high stability of the microbiota after high-fat diet loading compared to the control.

[0054]

[0070] Figure 5 shows the effect of the intervention on alpha diversity (defined as the diversity of microorganisms present in an ecosystem). The intervention significantly increases the alpha diversity of the ecosystem before high-fat diet challenge. Furthermore, the intervention keeps the alpha diversity stable during high-fat diet challenge.

[0055]

[0071] FIG. 6 demonstrates that the microbiota is less perturbed by a high-fat diet when nutritional intervention is performed.

[0056]

[0072] Figure 7 shows the changes in microbiota community structure (defined as the number and specificity of interactions between the constituent bacteria of the microbiota). The intervention maintains the number and specificity of interactions during high-fat feeding.

[0057]

[0073] Figures 8A-8C show the results for the resistance index. Figure 9 shows the results for the recovery index. The intervention shortens recovery time after a high fat meal challenge.

[0058]

[0074] Figure 10 is a graph showing the difference in metabolic composition relative to baseline. The intervention reduces the changes in metabolic level caused by high-fat loading. This effect is particularly evident two days after the end of the high-fat loading.

[0059]

[0075] Figure 11, Figure 12A and Figure 12B show the effect on the host in clinical studies. Specifically, Figure 11 shows that nutritional intervention normalizes the number of bowel movements during loading. Figures 12A and 12B show that nutritional intervention prevents the increase in antibodies against endotoxin levels in the blood induced by a high-fat diet. This prevention leads to an improvement of the intestinal barrier and the prevention of endotoxemia.

[0060]

[0076] This rigorous randomized controlled clinical study demonstrates that consumption of a fiber blend in combination with a probiotic mixture improves microbiome resilience, intestinal transit, and intestinal barrier and prevents endotoxemia in subjects challenged with a high-fat, low-fiber diet.

[0061]

[0077] It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages. Accordingly, such changes and modifications are intended to be encompassed by the appended claims.

Claims

1. A composition for enhancing the resilience of a target microbiome, the composition comprising a combination of at least one type of fiber and at least one type of probiotics, and being for administration to the target.

2. The composition according to claim 1, wherein the target has experienced, is about to experience, and / or has recently experienced a microbiome stressor.

3. The composition according to claim 2, wherein the stressor is selected from the group consisting of dietary stressors; antibiotics; other drugs; infections; intense exercise; stress; alcohol; travel; parenteral nutrition; enteral nutrition; short bowel syndrome; intestinal inflammation; chemotherapy; colon cancer; diarrhea; proton pump inhibitors; gluten-free diet; diet free of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP); and combinations thereof.

4. A composition for achieving at least one result selected from the group consisting of (i) prevention or attenuation of microbiome disruption; (ii) recovery after microbiome disruption; and (iii) normalization of one or more of bowel movement frequency, intestinal transit, constipation, intestinal permeability, endotoxemia, and intestinal barrier function, the composition comprising a combination of at least one type of fiber and at least one type of probiotics, and administration of the composition to the target enhancing the resilience of the target's microbiome.

5. A composition for improving gastrointestinal health, the composition comprising a combination of at least one type of fiber and at least one type of probiotics, and administration of the composition to the target enhancing the resilience of the target's microbiome.

6. The composition according to any one of claims 1 to 5, wherein the fiber is selected from the group consisting of insoluble fiber, soluble fiber, and mixtures thereof.

7. The composition according to claim 6, wherein the fiber is selected from the group consisting of xylooligosaccharide, flax, partially hydrolyzed guar gum (PHGG), glucomannan, cellulose, prune powder, pectin, and mixtures thereof.

8. The composition according to any one of claims 1 to 5, wherein the fiber comprises at least two types of fibers.

9. The composition according to any one of claims 1 to 5, wherein the probiotics are selected from the group consisting of Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus rhamnosus, Bifidobacterium longum, Lactobacillus plantarum, Bifidobacterium bifidum, Lactobacillus gasseri, and mixtures thereof.

10. The composition according to any one of claims 1 to 5, wherein the probiotics comprise strains selected from the group consisting of Lactobacillus acidophilus La-14, Bifidobacterium lactis Bl-04, Lactobacillus rhamnosus GG, Bifidobacterium longum BL-05, Lactobacillus plantarum Lp-115, Bifidobacterium bifidum Bb-06, Lactobacillus gasseri Lg-36, and mixtures thereof.

11. The composition according to any one of claims 1 to 5, wherein the probiotics comprise at least two types of probiotic strains.

12. The composition according to any one of claims 1 to 5, wherein the composition is orally administered to the subject.

13. The composition according to any one of claims 1 to 5, wherein the subject is selected from the group consisting of human infants, human children, human youths, human adults, and human elderly, and animals.

14. A composition comprising a combination of at least one type of fiber and at least one type of probiotic, wherein the unit dosage form of the composition comprises an effective amount of a combination of at least one type of fiber and at least one type of probiotic effective to enhance the resilience of the microbiome of the subject to which it is administered.

15. A method for manufacturing a composition for enhancing the resilience of the microbiome of a subject to which the composition is administered, the method comprising the step of adding at least one type of fiber to at least one type of probiotic and optionally at least one type of additional ingredient.

16. The composition according to claim 3, wherein the stressor is a dietary stressor.

17. The composition according to claim 16, wherein the dietary stressor is a high-fat diet.

18. The composition according to claim 17, wherein the high-fat diet is a Western-type high-fat low-fiber diet or a ketogenic diet.

19. The composition according to claim 8, wherein the fiber comprises two, three, four, five, six, or seven types of fibers.

20. The composition according to claim 8, wherein the fiber comprises more than seven types of fibers.

21. The composition according to claim 13, wherein the animal is a companion animal.

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