Compositions and methods for improving gut and skin barrier function

Abstract

The present invention is directed to a dietary supplement composition for enhancing gut barrier and skin health comprising a therapeutically effective amount of: (a) at least one polysaccharide chosen from a fructo-oligosaccharide, a galacto-oligosaccharide, a xylo-oligosaccharide, and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity; (c) at least one source of insoluble dietary fiber having antioxidant activity; (d) at least one amino acid capable of supporting gut barrier integrity; (e) at least one source of resistant starch; and, optionally (f) at least one natural ingredient capable of protecting gastric function.

Description

Attorney Docket No. 0218-0013W01COMPOSITIONS AND METHODS FOR IMPROVING GUT AND SKIN BARRIER FUNCTIONField of the Invention

[0001] The present disclosure relates to orally administered supplement compositions and methods of improving gut health as well as increasing efficacy of probiotic supplements for improving skin health, especially skin impaired with a condition. Supplement compositions are provided comprising a resistant starch together with a blend of dietary fibers, amino acids, antioxidants and superfoods which, when taken on a consistent basis, help to mitigate gut inflammation, gut microbiome balance, intestinal barrier integrity and gut mucosal lining health. As a result, there is a positive impact on skin inflammation, skin barrier integrity and improvement in skin conditions when taking an additional probiotic supplement designed for gut dysbiosis associated with that skin condition.Background of the Invention

[0002] The effect of prebiotics on gut health and systemic health are evidenced on both the skin and the brain through what is now termed the skin-gut-brain-microbiome axis. The term axis indicates and adds emphasis to the connection between all these entities. The collective research on the gut microbiome has almost simultaneously created an understanding of the importance of the gut microbiome’s influence on all aspects of human health. The interplay between the gut microbiomc with both the brain, the skin, and many other organs has become an intense area of research fueled in part by rapid increases in availability and affordability of genetic sequencing systems.

[0003] There is a clear analogy between the gut and tire skin. Both are densely vascularized and play crucial immune and neuroendocrine roles. Additionally, while the skin is the barrier between our bodies and the external world, the intestinal barrier is the barrier between our bodies and the vast array of organisms with which we have a symbiotic existence. As Salem et al. noted very clearly: "Cumulative evidence has demonstrated an intimate, bidirectional connection between the gut and skin, and numerous studies link gastrointestinal health to skin homeostasis and allostasis."

[0004] Put more succinctly, the gut-skin axis is the 2-way communication between the gut microbiome and the skin. It is good to emphasize that 2-way here means bidirectional; the gut can influence the skin, but the skin can also influence the gut. An example of the less frequently mentioned direction (the skin to the gut) is found in the production of vitamin D. Human skin creates vitamin D in response to exposure to UVB light and this circulating vitamin D is known to enhance the gut microbiome diversity.Attorney Docket No. 0218-0013W01

[0005] Analogously, the brain-gut axis is the 2- way communication between the brain and the gastrointestinal tract. When the gut integrity is compromised, it can influence emotional activity in the brain, and the brain can also regulate gastrointestinal function in the gut. For example, stomach or intestinal distress can be directly caused by anxiety, stress, or depression.

[0006] Moreover, the gut-brain axis also plays an important role in maintaining homeostasis. Many intrinsic and extrinsic factors influence signaling along this axis, modulating tire function of both the enteric and central nervous systems. Another aspect of this bidirectional link is the vagus nerve, which is one of the largest nerves that connects the gut and brain, allowing for transmission in both directions. Studies have shown that stress can inhibit the signals sent through the vagus nerve resulting in gastrointestinal problems. The role of the microbiome as an important factor in modulating gut-brain signaling has also emerged and tire concept of a microbiota-gut-brain axis has been firmly established. Another facet of the gut-brain connection can be noted in the fact that > 90% of the body’s most important neurotransmitter (serotonin) is produced in the gut (enterochromaffin cells) and only about 5% in the brain. Serotonin (5-HT) is a primary chemical messenger, and it affects many physiological processes and behaviors in the body including mood, memory, sleep, and digestion.

[0007] As described, the axes are linked as the gut can influence the brain, and brain can in turn influence the skin, often leading to a feedback loop. The gut can influence the skin, and in a concrete example of skin gut brain connection - a compromised gut can lead to skin disorders. Hie appearance of these disorders can lead to emotional distress when in turn further disrupts tire function of the gut and its microbiome.

[0008] Despite all the research of the last 30 years, there are still some fundamental unknowns with respect to the human gut microbiome. For example, to date there is still no single universal definition of what constitutes a healthy human gut microbiome; however, it is becoming abundantly clear what constitutes an unhealthy gut microbiome. Despite the lack of an understanding of what constitutes a global optimum gut microbiome, there are microbiome studies which likely characterize what can be considered a local optimum. For example, there are studies of tribes in the Amazon and hunter gatherer tribes in Tanzania. These groups represent cohorts that do not eat processed food, or use antibiotics, and are minimally exposed to Western influences. Study of their microbiomes reveals distinct differences in the makeup of their microbiomes as compared to a someone from a Westernized region. There is a broader diversity of species present and different ratios of relative abundance. The full implications of these differences are not yet completely understood. So, while the absolute optimal gut microbiome cannot yet be fully described, there are plenty of indications of what is not healthy. Concretely, we know that abundances of certain pathogenic species are not healthy (e.g., certain E. coli strains, H. pylori). WeAttorney Docket No. 0218-0013W01 also know that certain ratios being out of known bounds are also correlated to poor health. A great example, the Firmicutes / Bacteroidetes (F / B) ratio, is widely accepted as being a marker for normal intestinal homeostasis with the optimal ratio thought to be between 0.8 and 4.0. It should be noted that the ratio is age dependent and is not to be used as the sole diagnostic, but can be of significance as follows:

[0009] Interpreting the Ratio:

[0010] Studying the intestinal tract, its structure, and its contents is a holistic way to understand the importance and effect of changes to the relative abundances and overall population statistics of tire gut microbiome as well as the health and integrity of tire gastro-intestinal barrier itself. The intestines, like the skin, form a barrier critical for survival. The intestinal epithelium is the largest internal contact site in the human body. It selectively separates the body from the wet chemistry that is essential for existence. Tire gastrointestinal epithelial barrier, like the skin, protects against ingress by foreign antigens and microorganisms while allowing the absorption of essential nutrients and fluids. With this known, the gastro-intestinal barrier and an understanding of what influences its integrity has become an active and important area of study. The intestinal barrier is made up of 4 layers. Proceeding from inside the intestinal wall to the outside, the layers, or barriers as they are often referred to, are the microbial barrier, the biochemical barrier, the physical barrier, and immunological barrier.

[0011] Many researchers believe that the lack of a healthy gut microbiome is directly responsible for many of the cases of "leaky gut"; specifically, situations where a healthy gut microbiome has become unhealthy and finally leading to a state where the barriers have broken down and the intestinal wall integrity is compromised.

[0012] As referenced above, it is widely believed that the health of the intestinal microbiome affects tire integrity of the intestinal barrier. When tire integrity of the intestinal barrier is compromised, the ability to be selectively permeable is also compromised. Selectively permeable here meaning that water and electrolytes can pass through, but that the intestinal barriers block transit (to first order) of the contents of the intestines into the body as a whole. Violation of the integrity of the intestinal barrier results in diminished efficacy of one or many constituent barriers and can result in the uncontrolled passage ofAttorney Docket No. 0218-0013W01 bacterial components, products of bacterial metabolism, and the other substances living in as part of, or created by, the gut microbiome. This lack of selective permeability can result in "translocation"; many of the bacteria, their byproducts and toxins (e.g. endotoxins) move outside of the gut and create both systemic and local inflammatory responses often associated with disease states. Hence, dysbiosis in the skin and / or gut microbiome is associated with an altered immune response / systemic inflammation, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris, dandruff, and even skin cancer. Dysbiosis, lack of gut barrier integrity, and translocation are also associated with many other diseases - not only those of the skin.

[0013] What leads to dysbiosis and to a breakdown in intestinal integrity? The integrity of the intestinal barrier can be weakened by many things including exposure to environmental factors such as antibiotics, infections, diseases, chemical exposure, pesticides, micro or nano plastics, tobacco smoke, pollution, and many others. As previously mentioned, tire integrity of tire intestinal barrier can also be compromised by a change in the gut microbiome: it has also been noted that a change in intestinal barrier leads to a potential change in the gut microbiome; and the gut microbiome is also potentially altered by the environmental factors listed above. This change in the makeup of the microbiome as reflected in the relative population abundances and the number of different species / strains, and the expansion of pathogenic species. These changes have been shown to possess the potential to lead to a break in containment by the intestines. Tire effect of disruption of the intestinal barrier is often euphemistically referred to as "leaky gut."

[0014] The changes in the composition of the gut microbiome referred to above are known as dysbiosis. Dysbiosis can be summarized succinctly as being one or all the following changes in the gut microbiome: Expansion of the pathobiont (the community of resident microorganisms with pathogenic potential)A reduction in the diversity of speciesTire loss of commensal and / or beneficial microbes

[0015] There are still unknowns with respect to the relationships between all the human body’s cells, systems, organs and the resulting substances that damage the epithelial barrier, the intestinal microbiota, and the immune system. This means that tire re are still many questions regarding the details of tire changes that result in inflammation and the changes in cell function that ultimately result in the development of diseases. Many inflammatory disorders are now thought to be a direct result of actions by and / influence of bacterial species found in almost every healthy human. Again, the mechanism(s) by which each of these species becomes pathogenic have not been fully elucidated, but it appears that genetic defects and / or environmental factors may predispose us to immune-mediated diseases triggered by potentially pathogenic symbionts of the microbiota.Attorney Docket No. 0218-0013W01

[0016] As discussed, dysbiosis can lead to impairment of the gut integrity and disruption of the mucosal firewall can impact the homeostasis of the skin. Specifically, as noted by Mahmud et al.: The microbial communities maintain the gut barrier integrity mainly by converting undigcstiblc complex polysaccharides into vitamins (specifically K and B12), and SCFAs (specifically butyrate and propionate). For example, as butyrate is critical for epithelial barrier integrity, it also reduces the intestinal barrier permeability. The mucus layer of the gut acts as the primary barrier and prevents microbial relocation to other host tissues, The gut mucosal defense and gut barrier as a whole are aided by innate immune cells of the GALT (gut associated lymphatic tissue) cells. They recognize nonspecific infections and activate both the innate and adaptive immune systems by presenting those antigens. When these barriers arc breached, toxic byproducts of cell metabolism reach many parts of the body, and especially the skin.

[0017] There are many other ways that dysbiosis deleteriously affects the health and appearance of the skin. Certain pathogenic bacteria, such as Clostridium difficile (C. diff). produce p-cresol and phenol, which are metabolic byproducts of aromatic amino acids. These metabolites can enter the circulatory system, and they preferentially accumulate in the skin. This often results in impaired epidermal differentiation and compromises the skin barrier integrity. Additionally, high p-cresol serum levels are associated with reduced skin hydration and impaired keratinization. All of this results in chronic inflammation in the skin, which is seen in many skin diseases. Hie inflammation exacerbates skin barrier impairment, and results in conditions which allow increased rate of moisture loss and simultaneously increased access for adventitious agents which can lead to infection. Another simpler view is that the disrupted intestinal barrier leads to a disrupted skin barrier, directly affecting the local skin microbiome resulting in a loss of homeostasis. Loss of homeostasis and change in the microbiome is directly correlated with atopic dermatitis where S. aureus has been implicated.

[0018] The release of proinflammatory cytokines changing the intestinal permeability and the resulting cycle is thought to be a factor in multiple skin diseases, including acne, psoriasis, rosacea, and atopic dermatitis.

[0019] The study of the compromised gut barrier resulting from dysbiosis suggests intervention and therefore mitigation of some of the issues might be possible. Given the recent advent of the prebiotic, there is a relative dearth of detailed studies when compared to the body of work describing mechanisms and efficacy of probiotics. While this is changing the relatively nascent state is reflected in the public awareness and availability of prebiotics targeted at specific health issues.

[0020] Prebiotics, including polysaccharides, oligosaccharides and other fermentable dietary’ fibers and the subcategory of resistant starches, have been found to be beneficial to the overall gut microbiome byAttorney Docket No. 0218-0013W01 increasing beneficial Bifidobacterium and Lactobacillus species. These species help restore homeostasis thereby helping to repair the compromised gut barrier and mitigate the inflammatory response. Both are linked to enhanced production of immunoglobulin A (IgA), the primary antibody in the mucosal layer.

[0021] Resistant starches, so named owing to their resistance to digestion in the upper intestinal tract reach the colon substantially unchanged. In the colon, fermented resistant starches are facilitated by specific bacterial populations, leading to an increase in the production of short-chain fatty acids (SCFA) predominantly acetate, propionate, butyrate, and lactate. The first three (acetate, propionate, butyrate) act as carbon sources for the intestinal epithelial cells and while each play an important role in gut health, albeit with slightly different functions. Propionate is primarily utilized by the liver, whereas a significant amount of acetate enters systemic circulation and reaches peripheral tissues butyrate is generally considered to be the most beneficial owing to its role as the primary energy source for the colonocytes. Butyrate is known to enhance the immunity of the mucosal lining. It is also known that histamine from our diet and gut microbes can lead to intestinal distress and skin issues, especially for those with histamine intolerance. Recent work has shown that resistant starch, in particular, resistant potato starch consumption reduces serum histamine levels afflicted with increased intestinal permeability. The reduction in histamine production was correlated with increased levels of Bifidobacterium and Akkermansia in the gut. Th i s fits well with research indicating that both species of gut microbiota are linked to increased butyrate production.

[0022] When the gut associated lymphoid tissues encounter bacterial metabolites such as SCFAs produced from resistant starch fermentation, their activity is modulated, leading to an increased production of regulatory T cells which are involved in the control and damping of inflammation and autoimmunity.

[0023] Resistant starch fermentation byproducts can influence the integrity of the gut barrier. Tight junction proteins which maintain the continuity of the intestinal epithelial layer are upregulated by SCFAs. This aids in barrier function and reduces potential for translocation of byproducts of bacterial metabolism and other pathogens as discussed earlier.

[0024] Resistant starch acts as a prebiotic, selectively nourishing commensal bacterial populations, which in turn positively modulate immune responses. For instance, the enrichment of beneficial bacteria like Bifidobacteria and Lactobacilli, commonly associated with consumption of resistant starches, is linked to enhanced production of immunoglobulin A (IgA), the primary antibody in mucosal defense.Attorney Docket No. 0218-0013W01

[0025] Fructo-oligosaccharides (FOS), another known prebiotic has been correlated to improvement of gut dysbiosis and attenuation of inflammation in obese and diabetic patients. It has been confirmed that FOS supplementation can improve the pathological changes that lead to these health conditions.

[0026] Galacto-oligosaccharides (GOS) have also been correlated to positive health outcomes. They have been shown to have positive effect on bone composition and structure, they have been shown to support a healthy gut microbiome in infants and modulate the immune response in support of a healthy immune system. Finally. GOS has been noted to affect the postnatal immune development by influencing the gut microbiome. Specifically, GOS was thought to modulate the immune development to prevent the development of allergies in infancy.

[0027] It is therefore an object of the present disclosure to provide a dietary supplement composition which, when administered regularly, can help reduce inflammation in the gut and skin by:• mitigating microbiome dysbiosis while supporting beneficial gut bacteria• fortifying intestinal barrier integrity (e.g., by increasing butyrate production)• reducing gut inflammation• improving the quality of mucosal lining (e.g., by stimulating the production of mucin)• improving digestion through better absorption (e.g., by enhancing vitamin absorption).Summary of the Invention

[0028] The present disclosure relates to compositions and methods useful for dietary augmentation to provide therapeutic intervention for mitigating skin inflammation and skin barrier breakdown resulting from gut inflammation, dysbiosis, reduced gut barrier integrity and poor gut mucosal lining quality.

[0029] According to one embodiment of the present disclosure, there is provided an orally administrable composition containing: (a) at least one prebiotic oligosaccharide selected from fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity: (c) at least one source of insoluble dietary fiber having antioxidant activity: (d) at least one amino acid capable of supporting gut barrier integrity; and (e) at least one source of resistant starch.

[0030] According to yet another embodiment, there is provided an orally administrable composition containing: (a) from about 0.1 to about 10 grams of at least one prebiotic oligosaccharide selected from fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, and mixtures thereof; (b) from about 0. 1 to about 10 grams of at least one polysaccharide mucilage having demulcent activity; (c) from about 0. 1 to about 10 grams of at least one source of insoluble dietary fiber having antioxidant activity;Attorney Docket No. 0218-0013W01(d) from about 0.1 to about 10 grams of at least one amino acid ; and (e) from about 0.1 to about 10 grams of at least one source of resistant starch, all weights based on the total dry weight of the composition. In some embodiments, the amounts per unit dose on a dry-weight basis. In some embodiments, the amino acid is capable of supporting gut barrier integrity.

[0031] According to yet another embodiment, there is provided an orally administrable composition containing: (a) from about 0.5 to about 5.0 grams of at least one prebiotic oligosaccharide selected from fructo-oligosaccharide, galacto-saccharide, xylo-oligosaccharide, and mixtures thereof; (b) from about 0.2 to about 5.0 grams of at least one polysaccharide mucilage having demulcent activity; (c) from about 0.5 to about 5.0 grams of at least one source of insoluble dietary fiber having antioxidant activity; (d) from about 0.5 to about 5.0 grams of at least one amino acid; and (e) from about 1.0 to about 7.5 grams of at least one source of resistant starch, all weights based on the total dry weight of the composition. In some embodiments, the amounts per unit dose on a dry-weight basis. In some embodiments, the amino acid is capable of supporting gut barrier integrity.

[0032] In yet another embodiment of the present disclosure, there is provided an orally administrable composition containing: (a) from about 0.5 to about 3.0 grams at least one prebiotic oligosaccharide selected from fructo-oligosaccharide, galacto-oligosaccharide, xylo-oligosaccharide, and mixtures thereof; (b) from about 0.2 to about 2.0 grams of at least one polysaccharide mucilage having demulcent activity; (c) from about 0.5 to about 2.5 grams of at least one source of insoluble dietary fiber having antioxidant activity; (d) from about 0.5 to about 2.5 grams of at least one amino acid; and (e) from about 2.0 to about 5.0 grams of at least one source of resistant starch, all weights based on the total dry weight of the composition. In some embodiments, the amounts per unit dose on a dry-weight basis. In some embodiments, the amino acid is capable of supporting gut barrier integrity.

[0033] In some embodiments, the prebiotic oligosaccharide comprises fructo-oligosaccharide (FOS) and galacto-oligosaccharide (GOS) in a ratio by weight of about 1:2, respectively. In some embodiments, the prebiotic oligosaccharide comprises FOS and xylo-oligosaccharide (XOS) in a ratio by weight of about 1:2, respectively.

[0034] In some embodiments, the composition described herein further comprises (f) at least one natural ingredient capable of protecting gastric function. In some embodiments, component (f) is about 0.01 to about 1 grams, by total dry weight of the composition.

[0035] In another embodiment, there is provided a method of improving gut and skin barrier function to mitigate gut and skin inflammation, comprising orally administering the above-disclosed compositions to a human subject in need thereof.Attorney Docket No. 0218-0013W01Brief Description of the Drawings

[0036] FIG. 1 is a rear (posterior) view photograph of a test subject’s lower limbs illustrating severe eczema symptoms prior to starting their clinical trial.

[0037] FIG. 2 is a rear (posterior) view photograph of the same test subject’s lower limbs illustrating the effects on their eczema symptoms at tire conclusion of their clinical trial.Detailed Description of the Invention

[0038] The compositions of tire present invention can comprise, consist essentially of, or consist of, the components of the present invention as well as other ingredients described herein.

[0039] The term ‘"comprising” as used herein is meant to include various optional, compatible components that can be used in the compositions of the present disclosure. The term “consisting essentially of’ as used herein means that tire composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the compositions or methods.

[0040] As used herein, the words “preferred”, “preferably” and variants thereof refer to embodiments of the disclosure that afford certain benefits under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not usefill and is not intended to exclude other embodiments from the scope of the disclosure.

[0041] Numerical ranges as used herein are intended to include every number and subset of numbers contained within that range, whether specifically disclosed or not. Further, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers within that range.

[0042] All percentages, parts, proportions, and ratios as used herein are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level. In some embodiments, the composition is a unit dose composition, and the amounts are per unit dose on a dry weight basis.

[0043] As used herein, "dermatitis" refers to skin disorders which present with at least one of the following symptoms: inflammation, blisters, skin that is itchy, burning, crusty, thick, and scaly, pimples, pustules, and a compromised skin barrier.Attorney Docket No. 0218-0013W01

[0044] The phrase "therapeutically effective amount" as used herein refers to an amount that, when administered to a subject suffering from gut permeability, microbiome dysbiosis, inflammation and / or mucosal lining impairment, exhibits an effect of mitigating these symptoms in the gut barrier and thereby by improves the skin barrier as well.

[0045] As used herein, "orally administering'’ refers to taking the composition of the present disclosure by mouth on a daily basis.

[0046] The inventors have surprisingly and unexpectedly discovered that the use of compositions, e.g., dietary supplement compositions, in accordance with the present disclosure can help reduce inflammation in both the gut and skin by: mitigating microbiome dysbiosis while supporting beneficial gut bacteria; fortifying intestinal barrier integrity (e.g., increasing butyrate production); reducing gut inflammation (e.g., increase collagen production); improving the quality of mucosal lining (e.g., stimulate the production of mucin); improving digestion through better absorption (e.g., vitamin absorption); and regularizing motility.

[0047] According to an embodiment of the present disclosure, there is provided a composition for mitigating gut and skin inflammation comprising: (a) at least one prebiotic oligosaccharide selected from a fructo-oligosaccharide, a galacto-oligosaccharide, a xylo-oligosaccharide, and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity; (c) at least one source of insoluble dietary7fiber having antioxidant activity; (d) at least one amino acid capable of supporting gut barrier integrity; and (e) at least one source of resistant starch, wherein tire composition is administered orally.

[0048] Tire prebiotic oligosaccharide (POS) of the present disclosure are well-known carbohydrates that remain undigested until they reach the colon, where they are metabolized by tire gut microbiota.Fermentation of POS by the gut microbiota encourages the growth and activity of the gut microbial community and has been demonstrated to enhance levels of Bifidobacterium and Lactobacillus.

[0049] POS may be employed in the composition, e.g., dietary supplement composition, of the present disclosure in an amount of from about 0.01 to about 10 grams, in certain embodiments from about 0. 1 to about 10 grams, in some embodiments from about 0.1 to about 7 grams, in some embodiments from about 0.5 to about 5.0 grams, in some embodiments from about 0.5 to about 3.0 grams, or in some embodiments about 1 gram, all weights based on the total dry weight of the composition.

[0050] Fructo-oligosaccharides (FOS) are plant-derived oligosaccharides occurring in a wide variety of fruits, vegetables, and cereals. Chemically, FOS comprise one sucrose molecule linked to two, three, or four fructose units. They are produced commercially from sucrose using an enzymatic process or by partial hydrolysis of inulin (e g ., from chicory root, asparagus, Jerusalem artichokes, or soybeans).Attorney Docket No. 02f8-0013W01

[0051] FOS, a soluble fiber, may help with bowel regularity by increasing stool water content and bulk. When bacteria in the colon ferment FOS, they produce short-chain fatty acids (SCFAs) such as butyrate, support gut health. FOS may also help suppress the grow th of certain potentially harmful bacteria, such as Clostridium perfringens. Excess intake can cause gastrointestinal discomfort in some individuals.

[0052] FOS may be employed in the composition, e.g., dietary supplement composition, of the present disclosure in an amount of from about 0.01 to about 10 grams, in certain embodiments from about 0. 1 to about 10 grams, in some embodiments from about 0.05 to about 5.0 grams, in some embodiments from about 0.5 to about 3.0 grams, in some embodiments from about 0. 1 to about 1 gram, or in some embodiments about 1 gram, all weights based on the total dry weight of the composition.

[0053] Galacto-oligosaccharides (GOS) are non-digestible oligosaccharides composed primarily of galactose units, often with a terminal glucose. They are ty pically produced from lactose by an enzymatic reaction using p-galactosidasc; soybean-derived GOS are also known.

[0054] GOS may help with constipation, bloating, and abdominal discomfort, and may improve gut motility and stool consistency. GOS may also help reduce intestinal permeability and support lactose digestion in some individuals

[0055] GOS may be employed in the composition, e.g.. dietary supplement composition, of the present disclosure in an amount of from about 0.01 to about 10 grams, in certain embodiments from about 0. 1 to about 10 grams, in some embodiments from about 0.05 to about 5.0 grams, in some embodiments from about 0.5 to about 3.0 grams, in some embodiments from about 0.1 to about 1 grams, or in some embodiments about 1 gram, all weights based on the total dry weight of the composition.

[0056] In embodiments in which the prcbiotic oligosaccharide comprises both FOS and GOS, they may be present in a FOS:GOS ratio by weight of about 1:2.

[0057] Xylo-oligosaccharides (XOS) are oligosaccharides composed of xylose a C5 sugar). Suitable XOS may have a degree of polymerization of about 2 to about 10. XOS derived from com xylans have been used at daily amounts of about 1 gram in double-blind randomized studies and have been reported to increase Bifidobacterium relative to Lactobacillus over approximately? 8 weeks and to modulate the Firmicutes / Bacteroidetes ratio.

[0058] XOS may support digestion and nutrient absorption, help limit the growth of certain harmful bacteria by supporting commensal microbes, low er colonic pH level, and increase production of SCFAs (e.g., butyrate and propionate), which may support gut barrier integrity and immune function.Attorney Docket No. 0218-0013W01

[0059] XOS may be employed in the composition, e.g., dietary supplement composition, of the present disclosure in an amount of from about 0.01 to about 10 grams, in certain embodiments from about 0. 1 to about 10 grams, in some embodiments from about 0.05 to about 5.0 grams, in some embodiments from about 0.5 to about 3.0 grams, in some embodiments from about 0.1 to about 1 gram, or in some embodiments about 1 gram, all weights based on tire total dry weight of the composition.

[0060] In embodiments in which the prebiotic oligosaccharide comprises both FOS and XOS, they may be present in a FOS:XOS ratio by weight of about 1:2.

[0061] The composition of the present disclosure further includes at least one polysaccharide mucilage with demulcent activity to form a protective layer over mucosal membranes. An example is marshmallow root, which contains polysaccharide mucilage composed of L-rhamnose, D-galactose, D-galacturonic acid, and D-glucuronic acid. Marshmallow root yields a viscous mucilage that coats and soothes mucous membranes in the digestive tract (e.g., for heartbum, dyspepsia, constipation, or symptoms of gastroesophageal reflux). Its main constituents include mucilage, soluble fiber, tannins (root), flavonoids, phenolic acids, and coumarins.

[0062] In vitro and animal research suggests that marshmallow root extract has anti-inflammatory effects and may modulate phagocytosis and the release of inflammatory mediators and cytokines (e.g., interleukin-6 (IL-6) and tumor necrosis factor (TNF)) in immune cells.

[0063] The at least one polysaccharide mucilage with demulcent activity may be employed in an amount of from about 0.01 to about 10 grams, in certain embodiments from about 0.1 to about 10 grams, in some embodiments from about 0.2 to about 5.0 grams, in some embodiments from about 0.05 to about 5 grams, in some embodiments from about 0.2 to about 2.0 grams, in some embodiments from about 0.1 to about 1 gram, or in some embodiments about 0.5 grams, all weights based on the total dry weight of the composition.

[0064] The composition of the present disclosure further includes at least one source of insoluble fiber (e.g., dietary fiber) having antioxidant activity. Examples include, without limitation, pomace or fiber-rich fractions from aronia (chokeberry), pomegranate, artichoke, ginger root, coffee fruit, acai, acerola, camu camu, asparagus, and mangosteen.

[0065] Comparative studies have reported that fruit pomace often exhibits a higher total antioxidant activity than whole berries or juice, consistent with its higher total phenolic content. Predominant polyphenols in pomace include polymeric proanthocyanidins together with (-)-epicatechin. (-)- Epicatechin stimulates mitochondrial respiration and biogenesis, thus interfering with WarburgAttorney Docket No. 0218-0013W01 metabolism. At the cell signaling level, the compound inhibits Erk signaling, which interferes with other signaling pathways including EGFR that are known to be hyperactive in cancer.

[0066] Specific phenolic acids (e.g., chlorogenic and neochlorogenic acids) may be relatively higher in juice fractions.

[0067] For example, aroma berry pomace delivers soluble and insoluble fibers along with high concentrations of proanthocyanidins, epicatechin, and phenolic acids; consumption of aronia polyphenols has been reported to increase gut microbiome gene richness and the abundance of butyrate-producing species such as Lawsonibacter asaccharolyticus and Intestinimonas butyriciproducens.

[0068] As another example, pomegranate provides antioxidants (e.g. anthocyanins and other polyphenols) with anti-tyrosinase and anti-inflammatory activities. It contains ellagitannins and ellagic acid, which certain gut bacteria convert into urolithin A (UA). UA has been reported to enhance cellular health by promoting mitophagy and mitochondrial function and by modulating inflammation.

[0069] Studies suggest pomegranate extract may help maintain intestinal barrier integrity and is associated with beneficial changes in gut microbiota and inflammatory' protein profiles in human research.

[0070] Tire at least one source of insoluble fiber (e.g., dietary' fiber) with antioxidant activity may be employed in tire composition, e.g., dietary supplement composition, of the present disclosure in amounts of from about 0.01 to about 10 grams, in certain embodiments from about 0.1 to about 10 grams, in some embodiments from about 0.05 to about 5.0 grams, in some embodiments from about 0.5 to about 5.0 grams, in some embodiments from about 0.5 to about 2.5 grams, in some embodiments from about 0.1 to about 3.0 grams, or in some embodiments about 1.5 grams, all weights based on the total dry weight of the composition.

[0071] Tire composition of the present disclosure further includes at least one amino acid capable of supporting gut barrier integrity. L-glutamine, the most abundant amino acid in tire body, may support gut barrier function by helping regulate intestinal permeability and tight-j unction protein expression, supporting mucosal integrity, promoting enterocyte proliferation, modulating inflammatory responses, and helping normalize stool form and frequency.

[0072] Glutamine becomes especially important when bodily stores are depleted, which can occur during illness, injury, intense exercise, or physiological stress. For example, during high-intensity exercise, skeletal muscle demands for glutamine increases, potentially reducing availability to the intestines. Glutamine depletion can be associated with villus atrophy, decreased expression of tight junction proteins,Attorney Docket No. 0218-0013W01 and increased intestinal permeability, which may contribute to gastrointestinal complaints such as bloating, cramping, constipation, diarrhea, or abdominal discomfort.

[0073] The at least one amino acid may be employed in the composition, e.g., dietary supplement composition, of the present disclosure in an amount of from about 0.1 to about 10 grams, in certain embodiments from about 0.5 to about 5.0 grams, in some embodiments from about 0.5 to about 3.0 grams, in some embodiments from about 0.5 to about 2.5 grams, or in some embodiments about 1.0 gram, all weights based on the total dry weight of the composition.

[0074] The composition of the present disclosure further includes at least one source of resistant starch. Resistant starch is a carbohydrate fraction that resists digestion in the small intestine and is fermented in the large intestine. Resistant starch contributes to the maintenance of normal bowel function, supports regularity, and may enhance intestinal barrier function. Examples of suitable sources include, but are not limited to, high amylose maize starch (RS2), raw potato starch (RS2), cooked and cooled potatoes and rice (retrograded RS3), nuts, seeds, beans, legumes, whole grains, unripe bananas, and plantains.

[0075] Resistant potato starch has been reported to decrease histamine levels and visceral sensitivity in the gut and to support a favorable microbial balance (e.g., increased Bifidobacterium and Akkennansia), leading to increased butyrate production by F. prausnitzii and Megasphaera. ft has also been reported to reduce, circulating free fatty acid (FFA) levels, an early marker associated with metabolic dysfunction.

[0076] The at least one source of resistant starch may be employed in the composition, e.g., dietary' supplement composition, of the present disclosure in amounts of from about 0.01 to about 10 grams, in certain embodiments from about 0.1 to about 10 grams, in some embodiments from about 0.05 to about7.5 grams, in some embodiments from about 1 to about 7.5 grams, in some embodiments from about 0.1 to about 5 grams, in some embodiments from about 2 to about 5 grams, or in some embodiments about3.5 grams, all weights based on the total dry weight of the composition.

[0077] The composition of the present disclosure may further include at least one natural ingredient capable of protecting gastrointestinal (GI) function. GI function includes gastric emptying, small intestinal transit, colonic motility, and symptoms such as gas and bloating. Examples include, without limitation, ginger, peppermint, German chamomile, licorice, and cardamom.

[0078] Ginger root has been widely studied for its carminative effects - common uses include supporting relief of bloating, flatulence, and gas - as well as its protective effects on gastric emptying and gastric dysrhythmia. Gingerols may increase the rate of gastric emptying and support motility. Research also suggests that key actives in ginger (e.g.. zingiberene and gingerols) may increase protective prostaglandins in the gut wall and may inhibit certain pathogenic species such as Staphylococcus aureusAttorney Docket No. 0218-0013W01 and Escherichia coli. Shogaols in ginger have been shown in preclinical models to reduce inflammation and support the intestinal epithelial barrier in colitis.

[0079] The at least one natural ingredient capable of protecting GI function may be employed in the composition, e.g., dietary supplement composition, of the present disclosure in amounts of from about 0.01 to about 1 gram, in some embodiments from about 0.02 to about 0.5 grams, or in some embodiments from about 0.02 to about 0.1 grams, all weights based on the total dry weight of the composition.

[0080] In some embodiments, tire composition comprises: (a) from about 0.1 to about 10 grams by weight of the at least one prebiotic oligosaccharide; (b) from about 0.1 to about 10 grams by weight of the at least one polysaccharide mucilage; (c) from about 0. 1 to about 10 grams by weight of the at least one source of insoluble dietary fiber having antioxidant activity; (d) from about 0. 1 to about 10 grams by weight of at least one amino acid capable of supporting gut barrier integrity; and (e) from about 0.1 to about 10 grams by weight of the at least one source of resistant starch, all weights based on the total dryweight of the composition.

[0081] In some embodiments, (a) is employed from about 0.5 to about 5 grams by weight; (b) is employed in an amount of from about 0.2 to about 5 grams by weight: (c) is employed in an amount of from about 0.5 to about 5 grams by weight; (d) is employed in an amount of from about 0.5 to about 5 grams by weight; and (e) is employed in an amount of from about 1 .0 to about 7.5 grams by weight, all weights based on the total dry weight of the composition.

[0082] In some embodiments, (a) is employed in an amount of from about 0.5 to about 3.0 grams by weight; (b) is employed in an amount of from about 0.2 to about 2.0 grams by weight; (c) is employed in an amount of from about 0.5 to about 2.5 grams by weight; (d) is employed in an amount of from about 0.5 to about 2.5 grams by weight; and (e) is employed in an amount of from about 2.0 to about 5.0 grams by weight, all weights based on the total dry weight of the composition.

[0083] In some embodiments, (a) is employed in an amount of about I grams by weight; (b) is employed in an amount of about 0.5 grams by weight; (c) is employed in an amount of about 1.5 grams by weight; (d) is employed in an amount of about 1 grams by weight; (e) is employed in an amount of about 3.5 grams by weight; and (f) is employed in an amount of about 0.05 grams by weight, all weights based on the total dry weight of the composition.

[0084] According to one embodiment of the present disclosure, there is provided a composition, e.g., dietary supplement composition, capable of improving gut and skin barrier fimetion to mitigate inflammation in the gut and skin, the supplement comprising a therapeutically effective amount of: (a) about 1 gram of a prebiotic oligosaccharide containing chicory root fructo-oligosaccharide and xyloAttorney Docket No. 0218-0013W01 oligosaccharide; (b) about 0.5 grams of marshmallow polysaccharide demulcent; (c) about 1.5 grams of a blend of dietary fibers having antioxidant activity, wherein the blend comprises at least: (i) aronia fruit, (ii) pomegranate fruit, and (iii) artichoke leaf; (d) about 1 gram of L-glutamine; (e) about 3.5 grams of potato starch, and (f) at least 0.05 grams of ginger root, all weights based on the total dry weight of the supplement.

[0085] According to yet another embodiment, tire present disclosure is also directed to a method of improving gut and skin barrier function to mitigate inflammation in the gut and skin, comprising orally administering the above-disclosed dietary supplement compositions. In some embodiments, the method comprises oral administration to a human subject in need thereof.

[0086] In some embodiments, the method comprising administering a composition comprising: (a) at least one prebiotic oligosaccharide chosen from a fructo-oligosaccharide, a galacto-oligosaccharide, a xylo-oligosaccharidc, and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity; (c) at least one source of insoluble dietary fiber having antioxidant activity; (d) at least one amino acid capable of supporting gut barrier integrity; (e) at least one source of resistant starch; and, optionally (f) at least one natural ingredient capable of protecting gastrointestinal (GI) function.

[0087] In some embodiments, the at least one prebiotic oligosaccharide is employed in an amount of from about 0.1 to about 10 grams, or from about 0.1 to about 10 grams, or from about 0. 1 to about 7 grams, or from about 0.5 to about 5.0 grams, or from about 0.5 to about 3.0 grams, or about 1 gram, all weights based on the total dry weight of the composition.

[0088] In some embodiments, the at least one prebiotic oligosaccharide comprises fructo-oligosaccharide (FOS) in an amount of from about 0.01 to about 10 grams, or from about 0. 1 to about 10 grams, or from about 0.05 to about 5.0 grams, or from about 0.5 to about 3.0 grams, or from about 0.1 to about 1 gram, or in some embodiments about 1 gram, all weights based on the total dry weight of the composition.

[0089] In some embodiments, the at least one prebiotic oligosaccharide comprises galactooligosaccharide (GOS) in an amount of from about 0.01 to about 10 grams, or from about 0.1 to about 10 grams, or from about 0.05 to about 5.0 grams, or from about 0.5 to about 3.0 grams, or from about 0.1 to about 1 grams, or about 1 gram, all weights based on the total dry’ weight of the composition.

[0090] In some embodiments, the at least one prebiotic oligosaccharide comprises xylo-oligosaccharide (XOS) in an amount of from about 0.01 to about 10 grams, or from about 0.1 to about 10 grams, or from about 0.05 to about 5.0 grams, or from about 0.5 to about 3.0 grams, or from about 0.1 to about 1 gram, or about 1 gram, all weights based on the total dry weight of the composition.Attorney Docket No. 0218-0013W01

[0091] In some embodiments, the prebiotic oligosaccharide comprises both FOS and GOS. Tn some embodiments, the FOS:GOS ratio is about 1:2. In some embodiments, the prebiotic oligosaccharide comprises both FOS and XOS. In some embodiments, tire FOS:XOS ratio is about 1:2.

[0092] In some embodiments, the at least one polysaccharide mucilage is employed in an amount of from about 0.01 to about 10 grams, or from about 0.1 to about 10 grams, or from about 0.2 to about 5.0 grams, or from about 0.05 to about 5 grams, or from about 0.2 to about 2.0 grams, or from about 0.1 to about 1 gram, or about 0.5 grams, all weights based on the total dry weight of the composition.

[0093] In some embodiments, the at least one source of dietary fiber having antioxidant activity is employed in an amount of from about 0.01 to about 10 grams, or from about 0. 1 to about 10 grams, or from about 0.05 to about 5.0 grams, or from about 0.5 to about 5.0 grams, or from about 0.5 to about 2.5 grams, or from about 0. 1 to about 3.0 grams, or about 1.5 grams, all weights based on the total dry weight of the composition.

[0094] In some embodiments, the at least one amino acid capable of supporting gut barrier integrity is employed in an amount of from about 0.1 to about 10 grams, or from about 0.5 to about 5.0 grams, or from about 0.5 to about 3.0 grams, or from about 0.5 to about 2.5 grams, or about 1.0 gram, all weights based on the total dry weight of the composition.

[0095] In some embodiments, the at least one source of resistant starch is employed in an amount of from about 0.01 to about 10 grams, or from about 0.1 to about 10 grams, or from about 0.05 to about 7.5 grams, or from about 1 to about 7.5 grams, or from about 0. 1 to about 5 grams, or from about 2 to about 5 grams, or about 3.5 grams, all weights based on the total dry weight of the composition.

[0096] In some embodiments, the composition comprises at least one natural ingredient capable of protecting gastrointestinal (GI) function. In some embodiments, the at least one natural ingredient capable of protecting GI function is employed in an amount of from about 0.01 to about 1 gram, or from about 0.02 to about 0.5 grams, or from about 0.02 to about 0. 1 grams.

[0097] In some embodiments, the composition comprises: (a) from about 0.1 to about 10 grams by weight of the at least one prebiotic oligosaccharide; (b) from about 0.1 to about 10 grams by weight of the at least one polysaccharide mucilage; (c) from about 0. 1 to about 10 grams by weight of tire at least one source of insoluble dietary fiber having antioxidant activity; (d) from about 0. 1 to about 10 grams by weight of at least one amino acid capable of supporting gut barrier integrity: and (e) from about 0.1 to about 10 grams by weight of the at least one source of resistant starch, all weights based on the total dry weight of the composition.Attorney Docket No. 0218-0013W01

[0098] In some embodiments, (a) is employed from about 0.5 to about 5 grams by weight; (b) is employed in an amount of from about 0.2 to about 5 grams by weight; (c) is employed in an amount of from about 0.5 to about 5 grams by weight; (d) is employed in an amount of from about 0.5 to about 5 grams by weight; and (e) is employed in an amount of from about 1.0 to about 7.5 grams by weight, all weights based on the total dry weight of the composition.

[0099] In some embodiments, (a) is employed in an amount of from about 0.5 to about 3.0 grams by weight; (b) is employed in an amount of from about 0.2 to about 2.0 grams by weight: (c) is employed in an amount of from about 0.5 to about 2.5 grams by weight; (d) is employed in an amount of from about 0.5 to about 2.5 grams by weight; and (e) is employed in an amount of from about 2.0 to about 5.0 grams by weight, all weights based on the total dry weight of the composition.

[0100] In some embodiments, (a) is employed in an amount of about 1 grams by weight; (b) is employed in an amount of about 0.5 grams by weight; (c) is employed in an amount of about 1.5 grams by weight; (d) is employed in an amount of about 1 grams by weight: (e) is employed in an amount of about 3.5 grams by weight; and (f) is employed in an amount of about 0.05 grams by weight, all weights based on the total dry weight of the composition.REFERENCES• Salem et al., "The Gut Microbiome as a Major Regulator of the Gut-Skin Axis," Front. Microbiol. 9: 1459 (2018), doi: 10.3389 / fmicb.2018.01459• Margolis et al., "The Microbiota-Gut-Brain Axis: From Motility to Mood." Gastroenterology 160(5): 1486-1501 (2021), doi: 10.1053 / j.gastro.2020.10.066• Mahmud et al., "Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases," Gut Microbes 14(l):2096995 (2022), doi: 10.1080 / 19490976.2022.2096995• Thye et al., "Gut-Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis." 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Immunol. 10:277 (2019), doi:10.3389 / fimmu.2019.00277• Lin et al., "Butyrate and propionate protect against diet-induced obesity and regulate gut honnones via free fatty acid receptor 3-independent mechanisms," PLoS One. 7(4):e35240 (2012). doi: 10.1371 / joumal.pone.0035240• Zhao et al., "Resistant starch and the gut microbiome: Exploring beneficial interactions and dietary impacts," Food Chemistry: X 21: 101118 (2024) doi: 10.1016 / j.fochx.2024.101118• Pengrattanachot et al., "Tire impact of prebiotic fructooligosaccharides on gut dysbiosis and inflammation in obesity and diabetes related kidney disease," Food Funct. 13( 11):5925-5945 (2022), doi: 10.1039 / dlfo04428a• Mei et aL, "Biological activity of galacto-oligosaccharides: A review," Front Microbiol. 13:993052 (2022), doi: 10.3389 / fimcb.2022.993052• Moro et al., "A mixture of prebiotic oligosaccharides reduces the incidence of atopic dermatitis during the first six months of age," Arch Dis Child. 91( 10): 814-819 (2006) doi:10.1136 / adc.2006.098251• Roberfroid et al., "Prebiotic effects: metabolic and health benefits.," Br 1 Nutr. 104:S 1— 63 (2010), doi: 10.1017 / S0007114510003363• Gibson, "Dietary' modulation of the human gut microflora using the prebiotics oligofructose and inulin," J Nutr. 129: 1438S-1441S (1999), doi: 10.1093 / jn / 129.7.1438SAttorney Docket No. 0218-0013W01• Li et aL, "Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: a narrative review," Nutrients 13:3211 (2021), doi: 10.3390 / nul3093211• Tandon et al., "A prospective randomized, double-blind, placebo-controlled, dose-response relationship study to investigate efficacy of fructo-oligosaccharides (FOS) on human gut microflora," Sci Rep.9:5473 (2019), doi: 10. 1038 / s41598-019-41837-3.1• Mei et aL, Frontiers in Microbiology 13: 993052 (2022), doi: 10.3389 / fmicb.2022.993052; Hu et al., Adv. 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Sci. 18: 1051 (2017) doi: 10.3390 / ijmsl8051051• Deters et aL, Food Science and Human Wellness 10: 149-154 (2021)• Bush et al. , Nutrients 15: 1582 (2023). doi: 10.3390 / nul5071582• Bush et aL, Metabolites 14:536 (2024), doi: 10.3390 / metabol 4100536• Wang et aL, Frontiers in Microbiology 11:576061 (2021), doi: 10.3389 / fmicb.2020.576061• Bodagh et aL, Food Sci Nutr. 7:96-108 (2019), doi: 10.1002 / fsn3.807EXAMPLES

[0101] A composition in accordance with the present disclosure is found in Table 1 below.Table 1Attorney Docket No. 0218-0013W01

[0102] The composition of Example 1 was tested on a male individual suffering from severe eczema, as is seen in FIG. 1. The test subject was instructed to take the composition daily, as recommended, throughout the course of the study. He was also asked to provide fecal samples for testing / evaluation both prior to (baseline), and during, the study period.

[0103] Testing method:

[0104] The results were generated by extracting DNA from the fecal samples, amplifying the V1-V9 regions of the 16S ribosomal RNA sequences from the extracted DNA by polymerase chain reaction, and sequencing the products with a sequencing platform from Oxford Nanopore Technologies. The sequencing data was processed to ensure sufficient data quality and to obtain the taxonomic classification of each sequence. Results were collected from the individual’s fecal samples at three different times, namely, prior to testing to establish the individual’s baseline, and later at two other intervals approximately three months apart. The results were then compared to determine what, if any, improvements the individual experienced in terms of their gut microbiome diversity, as well as their eczema-related symptoms.

[0105] The test detects the presence of DNA belonging to particular species within the gut microbiome. Tire test explores the gut microbiome profile from various perspectives, focusing on:

[0106] Species Richness:

[0107] Examines the number of different microbial species present in the gut, which impacts the overall diversity and stability of the microbiome.

[0108] Species Composition at different taxonomical resolution levels:

[0109] Scrutinizes the proportion and distribution of bacteria at different taxonomical levels, from broad phyla to specific families, genera and species, to provide a more granular view' of microbial communityAttorney Docket No. 0218-0013W01 structure and function. This allows the potential to precisely identify key players within the ecosystem and to detect potential imbalances or dysbiosis.Table 2(*) Biodiversity of the microbiome was determined using the well-known Simpson’s Diversity Index.(**) F / B Ratio = Fcrmicutcs / Bactcriodctcs Ratio

[0110] While tire improvement in the overall state of the test subject’s microbiome can be seen from the above table, it is the “real-world” impact of this improved gut microbiome ecosystem that represents the most compelling proof of this supplements’ effect on gut microbiome health and, in turn, its efficacy in alleviating symptoms associated with chronic inflammatory skin disorders such as eczema. This validation or proof of concept is seen in the before and after photos of the test subject’s lower limbs in Figs. 1 and 2, where the reduction in eczematic symptoms is both startling and indisputable. The photos establish the “actual” impact of the technology when it comes to managing symptoms associated with inflammatory skin disorders such as eczema.

Claims

Attorney Docket No. 0218-0013W01What is claimed is:

1. A composition for improving gut and skin barrier function to mitigate gut and skin inflammation comprising: (a) at least one prebiotic oligosaccharide selected from a fructo-oligosaccharide (FOS), a galacto-oligosaccharide (GOS), a xylo-oligosaccharide (XOS), and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity; (c) at least one source of insoluble dietary fiber having antioxidant activity; (d) at least one amino acid capable of supporting gut barrier integrity; (e) at least one source of resistant starch; and. optionally (f) at least one natural ingredient capable of protecting gastrointestinal (GI) function.

2. The composition of claim 1, wherein (a) is employed in an amount of from about 0. 1 to about 10 grams by weight; (b) is employed in an amount of from about 0. 1 to about 10 grams by weight;(c) is employed in an amount of from about 0.1 to about 10 grams by w eight; (d) is employed in an amount of from about 0. 1 to about 10 grams by w eight; and (e) is employed in an amount of from about 0.1 to about 10 grams by weight, all weights based on the total dry weight of the composition.

3. The composition of claim 1. wherein (a) is employed in an amount of from about 0.5 to about 5 grams by weight; (b) is employed in an amount of from about 0.2 to about 5 grams by weight; (c) is employed in an amount of from about 0.5 to about 5 grams by weight; (d) is employed in an amount of from about 0.5 to about 5 grams by w eight; and (e) is employed in an amount of from about 1.0 to about 7.5 grams by weight, all weights based on the total dry weight of the composition.

4. The composition of claim 1. wherein (a) is employed in an amount of from about 0.5 to about 3.0 grams by weight; (b) is employed in an amount of from about 0.2 to about 2.0 grams by weight; (c) is employed in an amount of from about 0.5 to about 2.5 grams by weight; (d) is employed in an amount of from about 0.5 to about 2.5 grams by weight; and (e) is employed in an amount of from about 2.0 to about 5.0 grams by weight, all weights based on the total dry weight of the composition.

5. The composition of any one of claims 1-4, wherein the prebiotic oligosaccharide comprises both FOS and GOS in a ratio by weight of about 1:2, respectively.

6. The composition of any one of claims 1-4, wherein the prebiotic oligosaccharide comprises both FOS and XOS in a ratio by weight of about 1:2, respectively.Attorney Docket No. 0218-0013W017. The composition of any one of claims 1-6, wherein (f) is employed in an amount of from about 0.01 to about 1 grams, all weights based on the total dry weight of the composition.

8. The composition of any one of claims 1-7, wherein (a) is employed in an amount of about 1 grams by weight; (b) is employed in an amount of about 0.5 grams by weight; (c) is employed in an amount of about 1.5 grams by weight; (d) is employed in an amount of about 1 grams by weight; (e) is employed in an amount of about 3.5 grams by weight: and (f) is employed in an amount of about 0.05 grams by weight, all weights based on the total dry weight of the composition.

9. A method of improving gut and skin barrier function to mitigate gut and skin inflammation, the method comprising orally administering a composition comprising: (a) at least one prebiotic oligosaccharide selected from a fructo-oligosaccharide (FOS), a galacto-oligosaccharide (GOS), a xylo-oligosaccharide (XOS), and mixtures thereof; (b) at least one polysaccharide mucilage having demulcent activity; (c) at least one source of insoluble dietary fiber having antioxidant activity; (d) at least one amino acid capable of supporting gut barrier integrity: (e) at least one source of resistant starch; and, optionally (f) at least one natural ingredient capable of protecting gastrointestinal (GI) function.

10. Tire method of claim 9, wherein (a) is employed in an amount of from about 0.1 to about 10 grams by weight; (b) is employed in an amount of from about 0. 1 to about 10 grams by weight;(c) is employed in an amount of from about 0.1 to about 10 grams by weight; (d) is employed in an amount of from about 0.1 to about 10 grams by weight; and (e) is employed in an amount of from about 0.1 to about 10 grams by weight, all weights based on the total dry weight of the composition.

11. Tire method of claim 9, wherein (a) is employed in an amount of from about 0.5 to about 5 grams by weight; (b) is employed in an amount of from about 0.2 to about 5 grams by weight; (c) is employed in an amount of from about 0.5 to about 5 grams by weight; (d) is employed in an amount of from about 0.5 to about 5 grams by weight; and (e) is employed in an amount of from about 1 .0 to about 7.5 grams by weight, all weights based on the total dry weight of the composition.

12. Tire method of claim 9, wherein (a) is employed in an amount of from about 0.5 to about 3.0 grams by weight; (b) is employed in an amount of from about 0.2 to about 2.0 grams by w eight; (c) is employed in an amount of from about 0.5 to about 2.5 grams by weight; (d) is employed in an amount of from about 0.5 to about 2.5 grams by weight; and (e) is employed in an amount ofAttorney Docket No. 0218-0013W01 from about 2.0 to about 5.0 grams by weight, all weights based on tire total dry weight of the composition.

13. The method of any one of claims 9-12, wherein the prebiotic oligosaccharide comprises FOS and GOS in a ratio by weight of about 1:2, respectively.

14. Tire method of any one of claims 9-12, wherein the prebiotic oligosaccharide comprises both FOS and XOS in a ratio by weight of about 1:2, respectively.

15. The method of any one of claims 9 to 14, wherein (f) is employed in an amount of from about 0.01 to about 1 grams, all weights based on the total dry weight of the composition.

16. The method of any one of claims 9-15, wherein (a) is employed in an amount of about 1 grams by weight; (b) is employed in an amount of about 0.5 grams by weight; (c) is employed in an amount of about 1.5 grams by weight; (d) is employed in an amount of about 1 grams by weight; (e) is employed in an amount of about 3.5 grams by weight: and (f) is employed in an amount of about 0.05 grams by weight, all weights based on the total dry weight of the composition.

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