Compositions and methods for ameliorating and managing symptoms associated with eczema

Abstract

The present disclosure relates to compositions and methods useful for dietary augmentation to provide therapeutic intervention for the amelioration of symptoms associated with rosacea-prone skin. According to one embodiment of the present disclosure, there is provided an orally administrable composition containing a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (iii) Bifidobacterium longum, and (iii) Streptococcus thermophilus; and (b) at least one plant-based, antioxidant-rich source of fiber.

Description

Docket No. 0218-0012W01COMPOSITIONS AND METHODS FOR AMELIORATING AND MANAGING SYMPTOMS ASSOCIATED WITH ECZEMAField of the Invention

[0001] The present disclosure relates to orally administered supplement compositions and methods of ameliorating and managing symptoms associated with eczema. Supplement compositions are provided comprising a blend of probiotic species in combination with natural, antioxidant-rich sources of fiber which, when taken on a consistent basis, help to ameliorate, manage, and / or attenuate symptoms associated with atopic dermatitis, also called eczema.Background of the Invention

[0002] Eczema refers to a group of conditions that cause the skin to become itchy and inflamed. It occurs when an irritant or allergen, either from the environment or within the body, triggers the immune system, resulting in inflammation. This immune response can create the hallmark symptoms seen in most forms of eczema. Though it may sometimes be mistaken for other common conditions, such as hay fever, psoriasis, allergic reactions, or poison ivy, eczema can affect almost any part of the body, including the head, legs, arms, hands, and feet.

[0003] Typical symptoms of eczema include persistent itching, inflamed and crusted skin, as well as areas of dryness. In more severe cases, eczema can lead to blisters that may ooze clear fluid during flare-ups, along with the formation of thick, scaly patches. Since eczema compromises the skin's protective barrier, individuals with this condition are more susceptible to skin infections and may also be at higher risk for other skin disorders in affected areas.

[0004] In addition, eczema is often associated with a "leaky gut," i.e., when the integrity of the intercellular junctions in the intestinal lining is compromised. Along with skin barrier dysfunction that is characteristic of the disease, a correlation to a weakened intestinal barrier as also been noted, leading to increased gut permeability. Recent research has found correlation between gut bacteria Faecalibacterium prausnitzii and atopic dermatitis, and as markers of gut epithelial inflammation which can lead to barrier impairment. Specifically, the data suggests that feedback interactions between dysbiosis in Faecalibacterium prausnitzii and dysregulation of gut epithelial inflammation might be an underlying cause for chronic progression of atopic dermatitis resulting in impairment of the gut epithelial barrier which ultimately leads to aberrant TH2-typeDocket No. 0218-0012W01 immune responses to allergens in the skin. It is further thought that these gut markers are harbingers of intestinal barrier impairment, hence harbingers for many other disease states resulting from systemic inflammation.

[0005] There are seven distinct types of dermatitis, namely:

[0006] Atopic dermatitis is the most common form of eczema, characterized by inflammation, dryness, and itching of the skin. It often begins in childhood but can occur at any age.

[0007] Contact dermatitis, also known as allergic contact dermatitis, is triggered by environmental factors, such as allergens or irritants that encounter the skin.

[0008] Neurodermatitis, also referred to as discoid eczema, affects small, localized areas of skin, causing them to become itchy and develop scaly patches.

[0009] Dyshidrotic eczema results in dry, irritated skin, often accompanied by a burning sensation, as well as rashes and blisters.

[0010] Nummular eczema, also called nummular dermatitis, leads to the appearance of round, coin-shaped lesions, which typically occur on the arms and legs.

[0011] Seborrheic dermatitis, is an inflammatory form of eczema that primarily affects the scalp, causing redness, itching, and flaking.

[0012] Stasis dermatitis causes skin discoloration and inflammation, typically on the lower legs, often related to poor circulation.

[0013] In all of these cases, systemic inflammation drives activation of proteases and oxidative pathways that break down key structural and barrier proteins in the skin - especially extracellular matrix proteins (collagens, elastin, fibronectin, laminin), epidermal structural proteins (keratins, filaggrin, loricrin, involucrin, desmogleins), and basement-membrane components (type IV collagen, laminin). The result is thinning, fragility, impaired barrier function, loss of elasticity, delayed wound healing and easy bruising.

[0014] In recent decades, there has been a noticeable increase in atopic conditions, particularly in industrialized nations. This trend suggests that certain aspects of modern living are major contributors to this global issue. Factors such as consuming sterilized foods, improved hygiene practices, smaller family sizes, and the widespread use of antimicrobial and antibioticDocket No. 0218-0012W01 medications have led to fewer childhood infections. As a result, early exposure to microbes has decreased, which is believed to play a role in the development of the immune system.

[0015] Over the years, there has been a significant rise in allergic diseases, making them one of the most pressing health concerns in developed countries, affecting both children and adults. Recent data indicates that up to 40% of the population may be affected by atopic conditions, and this number continues to grow. Environmental factors are largely responsible for this increase, as they have a significant influence on the balance of microorganisms in the gastrointestinal tract.

[0016] This has led to growing interest in the potential role of products which help restore human microbiomes (e.g., probiotics) and aid in the prevention and treatment of allergic diseases. Other triggers that have been noted are both environmental and dietary. Specifically, air pollution through direct contact with the skin and dietary routes have been found to aggravate atopic dermatitis. The advent of highly processed foods, micro- and nano-plastics, as well as lower microbial diversity all add to this increase in atopic diseases.

[0017] Eczema can be triggered from within the body through a weakening of the intestinal barrier; eczema is often associated with a "leaky gut." Along with skin barrier dysfunction that is characteristic of atopic diseases, it is known that the intestinal barrier can also become more permeable leading to many issues - of note those that are issues related to the skin.

[0018] Atopic dermatitis (AD) is generally referred to as a chronic inflammatory skin disorder characterized by a compromised skin barrier, which leads to increased permeability. There is, however, a debate as to whether the compromised skin barrier results from gut issues, or whether from external influences. This is often referred to as the "Inside-out" hypothesis and the "Outside-in" hypothesis. Irrespective of this dichotomy, a weakened barrier makes the skin more susceptible to allergic reactions, elevates the skin's pH, and reduces its natural defenses against both resident and adventitious microbes, resulting in a higher likelihood of chronic, recurring inflammation.

[0019] Probiotics have been shown to play a key role in restoring gut barrier integrity by enhancing tight junction protein expression and reducing intestinal permeability. According to Cristofori et al., specific strains of Lactobacillus and Bifidobacterium can upregulate antiinflammatory cytokines like IL-10 while suppressing pro-inflammatory mediators such as TNF- a, thereby mitigating gut-derived systemic inflammation. (Cristofori et al., "Anti-InflammatoryDocket No. 0218-0012W01 and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body," Front Immunol. 12:578386; 2021.) These effects collectively strengthen the mucosal barrier and modulate immune responses, suggesting that probiotic supplementation may offer therapeutic potential in conditions, such as eczema, where leaky gut is implicated in disease progression.

[0020] The intestinal microbiota in individuals with atopic dermatitis (AD) differs from that of healthy individuals. In a healthy gut, beneficial species such as Lactobacillus (phylum Firmicutes) and Bifidobacterium (phylum Actinobacteria) are commonly present. However, in people with atopic diseases, microorganisms like Clostridium (phylum Firmicutes) and Staphylococcus (phylum Firmicutes) are more frequently found. These microbes are also more prevalent in children born via cesarean section, a group that is known to have an increased susceptibility to atopic conditions.

[0021] There are established therapeutic strategies for managing AD, such as promoting skin hydration, using emollients, avoiding allergens, and applying antihistamines and / or corticosteroids during flare-ups. These treatments mainly target symptom relief. Despite their benefits, these treatment modalities often fall short in providing long-term control, and recurrence rates including flare-ups remain high.

[0022] While the historical body of clinical studies on probiotics and atopic dermatitis remains ambiguous regarding efficacy, the consensus in the conventional medical community currently leans at best to implying that probiotics are not proven for the treatment of established atopic dermatitis but may be helpful in its prevention. This view of probiotics is starting to break down as genetic sequencing has afforded medical science a better window into which probiotics work for whom, when, and why. Additionally, attention is being focused on the condition of the gut microbiome and which species and strains are present / absent. Equivalently, increasing attention is also being focused on the particular strains delivered in probiotic supplements vis-a-vis the patient's own microbiome. In the gut, as with the skin, perturbations to the gut microbial diversity (e.g. change in relative populations of strains and species) may inhibit the maturation of the T-regulatory cells causing Thl and / or Th2 induced inflammation.

[0023] In recent years, various studies have explored the use of prebiotics, probiotics, and symbiotics as potential therapies for the treatment and management of AD and eczema. Probiotics commonly used in this context include bacteria from the Lactobacillus andDocket No. 0218-0012W01Bifidobacterium genera, as well as yeasts like Saccharomyces boulardii. These microorganisms naturally exist in the human gut flora and can survive the digestive process, making them suitable candidates for supplementation. The primary criteria for selecting these probiotics are their ability to reach the intestines alive and adhere to the intestinal walls, where they can exert their beneficial effects. However, there is growing recognition of the value of para-biotics and post-biotics. The term probiotics will be used here to include Parabiotics (aka paraprobiotic) and Postbiotics as many, if not the majority, of probiotic products on the market are not live or viable at delivery or past the initial stages of the gut / digestive system (e.g. stomach and small intestine) owing to the low pH environment.

[0024] Parabiotics are defined as inactivated, often intentionally, non-viable microbial cells whole cells, cell fragments, or crude cell preparations made from defined strains. These strains chosen such that, when given in adequate amounts, confer a health benefit. The effect is primarily via cell-associated structures like Microbe-Associated Molecular Pattern (MAMPs ) (e.g., peptidoglycan, lipoteichoic acid, teichoic acids, surface proteins). Parabiotics are also called "ghost" or "tyndallized" probiotics.

[0025] Postbiotics are defined as a preparation of inanimate microorganisms and / or their components that confers a health benefit. This can include whole inactivated cells, cell fragments, and associated cell components. Current consensus usage is described, e.g., by the International Scientific Association for Probiotics and Prebiotics (ISAPP), 2021. doi : 10.1038 / s41575-021 -00440-6. Previous definitions of postbiotics included cell-free microbial products (metabolites, peptides, short chain fatty acids / SCFAs, exopolysaccharides / EPS, bacteriocins) obtained from cultures or lysates with no cells present.

[0026] In the case where there is no need to repopulate a specific strain missing in the gut microbiome, but there is a need to modulate the immune response - non-viable probiotics (e.g. parabiotics and postbiotics) have demonstrated significant efficacy. In fact, for many applications they have equivalent effect as the live probiotic counterpart.

[0027] In commercial products, parabiotics, probiotics, and postbiotics may be combined inadvertently and are often referred to only as "probiotics."

[0028] As discussed above, there is growing evidence that the gut microbiome plays a crucial role in regulating systemic inflammation and influencing various diseases. While each person'sDocket No. 0218-0012W01 gut microbiome is unique, it can also be influenced by a wide range of external (exogenous) and internal (endogenous) factors, leading to changes in its composition and function. These fluctuations can impact overall health, including the body's inflammatory responses and susceptibility to conditions like AD.

[0029] Probiotics have been found to exhibit immunomodulatory effects by enhancing the intestinal barrier and reducing inflammation associated with allergic conditions such as AD. They inhibit the adherence of harmful pathogens to the intestinal epithelium and mucosal surfaces, preventing these pathogens from penetrating through the intestinal lining. By restoring the mucosal barrier function and breaking down food antigens, probiotics help reduce pathogen proliferation and, in turn, the inflammatory response.

[0030] Probiotics play a key role in improving gut permeability in individuals with AD by helping to restore the intestinal barrier's protective function and by reducing inflammation, or by reducing pathogen adhesion to the intestinal barrier. Several studies have demonstrated that probiotic treatment significantly reduces microbial translocation in AD patients, meaning fewer harmful microbes pass through the intestinal lining. Combining different probiotic strains has been shown to significantly enhance immunomodulatory activity, supporting the body's ability to maintain and strengthen epithelial barrier integrity. (lemoli et al., J Clin Gastroenterol. 46 Suppl:S33-40, 2012.) Additionally, probiotics help regulate the balance between Thl and Th2 cytokine responses, making them a promising adjunctive therapy for managing adult AD.

[0031] In AD, Th2 cells dominate over Thl cells, leading to an imbalance between these two immune cell types. This imbalance contributes to defects in filaggrin production, which weakens the skin barrier and diminishes its ability to protect against pathogens and allergens. It is thought that early exposure to microbial agents may promote Thl cell maturation and reduce the overactive Th2 response. Prebiotics also play a role by inducing regulatory T cells (Tregs) and modulating Toll-like receptors (TLRs), which can activate dendritic cells and promote the Thl immune response, or directly influence T-cells.

[0032] Furthermore, studies have indicated that probiotics may enhance Thl activity while repressing Th2 and Thl7 responses. Elevated Thl7 cell levels are often observed during acute AD flare-ups and are correlated with severity; therefore, reducing Thl7-driven inflammation may contribute to improved symptom control and reduced disease burden. The exactDocket No. 0218-0012W01 mechanisms by which each probiotic, live and / or dead and / or fragmented, exert this influence is still under study as it appears that each probiotic acts on different receptors in the intestinal wall, dendritic cells, and other cells.

[0033] The adult gastrointestinal tract is home to trillions of microbial cells. Research has identified approximately 9.9 million microbial genes in the human intestine, showcasing the immense complexity of the gut microbiome. This diverse community of microorganisms plays a crucial role in regulating numerous physiological processes, including intestinal hormone production, cell growth, blood vessel formation, biosynthesis of various compounds, and detoxification. Additionally, the gut microbiota is essential for modulating immune pathways and supporting the development and maintenance of the gut mucosal lining.

[0034] When the integrity of the intercellular junctions in the intestinal lining is compromised, i.e., leaky gut syndrome, the body's ability to regulate which substances enter the bloodstream is impaired. This can result in partial or complete loss of control over the agents that cross into the bloodstream, potentially causing health issues, including parasitic infections or vitamin deficiency.

[0035] The gut microbiota performs numerous essential functions in the body, including protective, metabolic, trophic (nutritional support), and immune roles. Its immune function is particularly significant in facilitating the elimination of antigens, thus contributing to the body's defense against harmful invaders.

[0036] The gut and skin, which are connected at the lips of the mouth and anus serve as a physical barrier to the outside and act as the body's first line of defense against harmful microorganisms. The innate immune system is capable of distinguishing between beneficial, commensal bacteria and harmful pathogens, ensuring that the adaptive immune system is not triggered by the normal, healthy bacteria that reside in the skin microbiome. It is believed that resident bacteria prevent the spread of pathogenic or non-resident bacteria by occupying key sites on the skin and gut, effectively blocking them from establishing themselves.

[0037] In addition, by-products of commensal bacteria have been found to directly influence the immune system. These bacteria can release antimicrobial peptides that work alongside the host's own peptides to selectively kill harmful pathogens. For instance, certain non-harmful strains ofDocket No. 0218-0012W01Staphylococcus have been shown to inhibit the growth of Staphylococcus aureus through this mechanism.

[0038] Therefore, maintaining a balance of commensal bacteria is crucial for proper immune function. Disruptions or imbalances in these resident microbes can weaken the immune response and contribute to inflammatory skin conditions, highlighting the integral role of the skin microbiome in overall skin health.

[0039] The Gut-Skin Axis (GSA) more directly highlights this connection between gut health and skin health, largely due to the gut's immunological and metabolic functions. While it is challenging to establish a direct cause-and-effect relationship between the gut microbiome and skin conditions, numerous studies have shown an association between gastrointestinal (GI) disorders and dermatological diseases. For instance, 10% to 25% of patients with GI diseases like ulcerative colitis, Crohn's disease, and celiac disease also exhibit skin manifestations, particularly psoriasis and cutaneous ulcers. Some skin symptoms linked to inflammatory bowel disease may reflect the degree of gut inflammation. Additionally, conditions such as celiac disease and dermatitis herpetiformis show a clear connection, with skin flares often coinciding with gut dysbiosis, especially following dietary triggers.

[0040] The exact mechanisms behind the interaction between the gut and skin remain unclear, though the immune and endocrine systems are believed to play critical roles. A common theory is that inflammation, whether in the gut or the skin, may be initiated by gut dysbiosis, which disrupts the balance of gut bacteria and triggers systemic inflammation. This inflammation can compromise skin homeostasis. One proposed mechanism involves gut imbalances activating T- cells and impairing immunosuppressive cytokines and regulatory T-cells (Tregs), which are essential for maintaining tolerance toward microbiota. This results in chronic inflammation in both the gut and skin, which the body's normal immune response is unable to control.

[0041] Another theory suggests that gut dysbiosis leading to increased intestinal permeability allows gut bacteria and / or pathogens (e g., endotoxins) to enter the bloodstream and other organs, further contributing to systemic inflammation. This effect is often referred to as "translocation." Studies have found higher levels of gut bacterial DNA in the bloodstream of patients with chronic skin conditions, which may exacerbate the immune response. Additionally, metabolic byproducts from gut bacteria can circulate and accumulate in the skin, potentially impairing keratinDocket No. 0218-0012W01 production and affecting epidermal differentiation. While this mechanism doesn't directly target the immune system, it weakens the skin barrier, making it more prone to inflammation and to the activities of adventitious agents. Diet also plays a role in this process; high fat intake can enhance the effect and proliferation of inflammatory bacteria in the GI tract, which may then enter the bloodstream through a weakened intestinal barrier.

[0042] The neuroendocrine relationship between the gut and skin microbiomes is driven by gut microorganisms' ability to activate neural pathways through the production of neurotransmitters such as norepinephrine, serotonin, and acetylcholine. These neurotransmitters prompt the release of hormones from enteroendocrine cells, leading to widespread inflammation that can impact the skin. For example, elevated serotonin levels may trigger the itch-scratch cycle, a key factor in the development of atopic dermatitis; approximately 90% of the body's serotonin is produced by enterochromaffin cells in the gut. Conversely, lower acetylcholine levels in atopic dermatitis lesions suggest that this neurotransmitter may play a protective role in preventing inflammation.

[0043] The GSA also plays a role in the development of atopy. Early-life dysfunction of the epithelial barrier can lead to sensitization to allergens and pathological immune activation. Mutations in the skin barrier protein filaggrin are linked to atopic dermatitis, asthma (“leaky lung”), intestinal permeability, and allergic sensitization, meaning that ingesting certain food allergens can worsen skin lesions in these individuals. While most studies focus on how the gut microbiome affects the skin, evidence suggests that the relationship may also work in reverse. For instance, in type I food-specific Ig-E-mediated allergic reactions, sensitization may occur through inflamed skin before food is even ingested, particularly during the first months of life. This indicates that exposure through compromised skin, rather than the GI tract, may initiate allergies. This also highlights the bidirectional nature of GSA. Additionally, patients with atopic dermatitis and a weakened skin barrier may experience gut epithelial sensitization, further contributing to the development of food allergies.

[0044] Currently, there is no definite treatment option for atopic dermatitis in modern medicinal practice, and disease control is based on: identification and avoidance of factors that stimulate a flare-up; sufficient hydration and moisturization of the skin; control of pruritus and infection; and usage of topical corticosteroids in mild cases. Severe and resistant cases are often treated with immunosuppressive medication. However, due to numerous adverse effects associated withDocket No. 0218-0012W01 immunosuppressive drugs and long-term corticosteroid use, safer therapeutic treatment is required.

[0045] As a result, there remains a need for the development of new therapeutic eczema treatment assets for managing eczema-prone skin with little to no negative side effects that are capable of effectively addressing the symptoms associated with inherent inflammation and gut dysbiosis, simultaneously.Summary of the Invention

[0046] According to embodiments, therapeutic compositions and supplements are provided comprising probiotic blends and plant-derived actives, and a method of treating eczema-prone skin.

[0047] The present disclosure relates to compositions and methods useful for dietary augmentation to provide therapeutic intervention for the treatment and management of eczema- prone skin. According to one embodiment of the present disclosure, there is provided an orally administrable composition containing a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (Hi) Bifidobacterium longum, and (iv) Streptococcus thermophilus; and (b) a plant based, antioxidant-rich source of fiber.

[0048] In another embodiment, there is provided a method of treating eczema-prone skin, comprising orally administering to a human subject in need thereof, a therapeutically effective oral dose of a composition containing: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (Hi) Bifidobacterium longum, and (iv) Streptococcus thermophilus; and (b) a plant-based, antioxidant-rich source of fiber.

[0049] These and other features, aspects and advantages of the present disclosure will become evident to those skilled in the art from a reading of the present disclosure.Brief Description of the Drawings

[0050] FIG. 1 shows the results of an open label study with 30 participants using the probiotic of Example 1 as described herein. In FIG. 1, "SCORAD" stands for SCORing Atopic Dermatitis.Docket No. 0218-0012W01Detailed Description of the Invention

[0051] The compositions of the present invention can comprise, consist essentially of, or consist of, the components of the present invention as well as other ingredients described herein. 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 the 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.

[0052] 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 useful and is not intended to exclude other embodiments from the scope of the disclosure.

[0053] 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.

[0054] 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.

[0055] As used herein, "eczema" refers to dermatitis-like skin disorders which present with at least one of the following symptoms: redness (or ashy tone in skin of color), inflammation, blisters, skin that is itchy, burning, crusty, thick, and scaly, and a compromised skin barrier.

[0056] The phrase "therapeutically effective amount" as used herein refers to an amount that, when administered to a subject suffering from eczema, exhibits an effect of ameliorating symptoms associated with eczema-prone skin.

[0057] As used herein, "treatment" or "treating" means the alleviation, prophylaxis or reversal of a condition, a disease, or a disorder, or at least a discernible symptom thereof. In one embodiment, "treatment" or "treating" refers to a mitigation, prophylaxis, or reversal of at least one measurable physical parameter or symptom related to the condition, disease, or disorderDocket No. 0218-0012W01 being treated, not necessarily discernible in or by the individual, being treated. In yet another embodiment, "treatment" or "treating" refers to inhibiting or slowing the progression of a condition, a disease, or a disorder, either physically, e.g., stabilization of a physiologically discernible symptom, e.g., stabilization of a physical parameter, or both. In yet another embodiment, "treatment" or "treating" refers to delaying the onset of a condition, disease, or disorder.

[0058] As used herein, the term "probiotics" is defined as substances which: a. stimulate the growth of gut microbiome based organisms, especially those with beneficial properties that give health benefits to the host when orally administered in an appropriate amount b. comprise metabolites and / or cell-wall components, secreted by live bacteria or released after bacterial lysis, with demonstrated beneficial activities in the host; c. include parabiotics and postbiotics, i.e., "other" terms by which probiotics are oftentimes referred, especially in commercial products. As discussed herein, postbiotics may induce anti-inflammatory, immunomodulatory, anti-obesogenic, anti-hypertensive, hypocholesterolemic, anti-proliferative, and antioxidant activities.

[0059] Their established safety and beneficial effects on human health have led to the emergence of probiotics as substitutes or complements to medicines. The advantage of probiotics is that they generally have very few side effects compared to typical western medical constructs.

[0060] The term "prebiotics" typically refers to foods having a high fiber content which can act as a food source for human microflora.

[0061] As used herein, the term "synbiotics" refers to dietary supplements comprised of both prebiotic and probiotic ingredients, the combination of which have immunomodulating and gastrointestinal flora-restoring activity.

[0062] As used herein, the acronym CFU stands for colony forming units.

[0063] As used herein, the term "inflammatory skin disorders" refers to skin conditions associated with inflammation including, for example, eczema (dermatitis) and psoriasis.

[0064] Skin barrier disfunction with dysbiosis, resultant impairment of immune tolerance / hypersensitivity, gut dysbiosis, leaky gut, food allergies, systemic chronic low-grade inflammation are all believed to play a role in the pathogenesis of eczema.Docket No. 0218-0012W01

[0065] That said, the inventors have surprisingly and unexpectedly discovered that the use of dietary supplement compositions in accordance with the present disclosure effectively ameliorate and manage inflammatory skin disorders, especially eczema, based on their ability to mitigate inflammatory mediators, support immunity, and restore skin barrier function via the gut-skin axis.

[0066] Accordingly, an object of the present disclosure is to provide compositions for ameliorating symptoms associated with eczema comprising a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (Hi) Bifidobacterium longum, and (iv) Streptococcus therm ophilus, and (b) at least one plant-based, antioxidant-rich source of fiber, wherein the composition is administered orally.

[0067] The Lactobacillus helveticus bacterium of the present disclosure is a beneficial bacterium commonly used as a probiotic. It is naturally found in the body, as well as in fermented foods and helps to support both the immune and digestive systems. It may be employed in the form of live cells or fermentation products (e.g., supernatants). Lactobacillus helveticus can improve digestion of dairy proteins, support intestinal barrier function, modulate local immune responses, produce antimicrobial compounds, and helping reduce some functional GI symptoms. Many people suffering from eczema are lactose intolerant, and this can be problematic for children in their growth phase. This bacterium can be beneficial as it enhances digestion of dairy proteins: strong proteolytic activity breaks down casein during fermentation, increasing digestibility and producing bioactive peptides that can alter gut physiology and peptide signaling.

[0068] In some embodiments, the amount of Lactobacillus helveticus bacterium employed depends on the age of the subject to whom the composition is administered, e.g., newborns to adults. In some embodiments, the Lactobacillus helveticus bacterium is employed in an amount of from about 0.1 to about 20 billion CFU, from about 0.2 to about 20 billion CFU, from about 0.5 to about 10 billion CFU, from about 0.1 to about 10 billion CFU, or about 5 billion CFU, or about 1 billion CFU. In some embodiments, the amount of Lactobacillus helveticus bacterium is about 5 billion CFU for individuals aged 13 years of age or older (" 13+"), and about 1 billion CFU for children up to the age of about 13. Here, "CFU" are specifically meant to represent all of the microbial population alive, dead, or its constituent.Docket No. 0218-0012W01

[0069] The J ctobacillus plantarum of the present disclosure is a species of lactic acidproducing, gram-positive, rod-shaped, anaerobic bacteria. L. plantarum is found in the human mouth and gastrointestinal tract, as well as in various fermented foods. L. plantarum differs from other lactobacilli because of its pseudo-catalase activity and ability to reduce nitrate. It has been shown to upregulate tight junction proteins and mucin production, help preserve epithelial integrity, and reduce intestinal permeability (leaky gut). It has also been shown to stimulate anti-inflammatory cytokines (e.g., IL-10), downregulate proinflammatory signaling (e.g., TNF-a, IL-6), and reduce neutrophil infiltration.

[0070] In some embodiments, the amount of Lactobacillus plantarum bacterium employed depends on the age of the subject to whom the composition is administered, e.g., newborns to adults. In some embodiments, the Lactobacillus plantarum bacterium is employed in an amount of from about 0.1 to about 20 billion CFU, from about 0.1 to about 10 billion CFU, from about 0.2 to about 2 billion CFU, or about 5 billion CFU, or about 1 billion CFU, or about 0.2 billion CFU. In some embodiments, the amount of Lactobacillus plantarum bacterium is about 1 billion CFU for individuals aged 13+ and about 0.2 billion CFU for children up to the age of about 13.

[0071] The Bifidobacterium longum of the present invention is a multifunctional probiotic that is effective in alleviating gastrointestinal, immunological and infectious diseases. It generally can benefit the gut by supporting barrier function, reducing inflammation, producing short-chain fatty acids, competing with pathogens, improving bowel habits, and modulating host immunity and the gut-brain axis. More specifically, it promotes tight-j unction protein expression and mucin production, lowering intestinal permeability. It can also stimulate regulatory pathways (e.g., increases IL-10, promotes regulatory T cells), lower proinflammatory cytokines, and reduce gut inflammation. Finally, it can also ferment carbohydrates to acetate and lactate (and promotes cross-feeding to butyrate producers), which nourish colonocytes, lower luminal pH, and support a healthy gut microbiome.

[0072] In some embodiments, the amount of Bifidobacterium longum bacterium employed depends on the age of the subject to whom the composition is administered, e.g., newborns to adults. In some embodiments, the Bifidobacterium longum bacterium is employed in an amount of up about 20 billion CFU, from about 0.1 billion to about 10 billion CFU, from about 0.1 to about 5 billion CFU, from about 0.2 to about 5 billion CFU, or about 2.4 billion CFU, or about 2 billion CFU, or about 0.5 billion CFU. In some embodiments, the amount of BifidobacteriumDocket No. 0218-0012W01 longum bacterium is about 2 billion CFU for individuals aged 13+ and about 0.5 billion for children up to the age of about 13.

[0073] The Streptococcus thermophilus is a non-pathogenic, Gram positive, generally recognized as safe (GRAS) bacterium. It provides several gut benefits, most reliably improving lactose digestion, which may be important in eczema, as many children and adults are lactose intolerant. It also can help gut barrier function, modulate immunity, inhibit pathogens, and support beneficial microbial metabolism. More specifically, it produces P-galactosidase (lactase) that breaks lactose into glucose and galactose during fermentation and transiently in the gut after ingestion. These can be cross-fed to butyrate-producing gut bacteria, supporting colonocyte health and anti-inflammatory short-chain fatty acid (SCFA) production. In addition, it may also stimulate mucin expression and strengthen epithelial defenses like its previous two counterparts, which supports mucus integrity and adhesion of beneficial microbes. Finally, it can increase secretory IgA in the gut and influence cytokine balance.

[0074] In some embodiments, the amount of Streptococcus thermophihis bacterium employed depends on the age of the subject to whom the composition is administered, e.g., newborns to adults. In some embodiments, the Streptococcus thermophilus bacterium is employed in an amount of from about 0.2 to about 20 billion CFU, from about 1 to about 20 billion colony forming units CFU, from about 0.5 to about 10 billion CFU, from about 1 to about 10 billion CFU, or about 5 billion CFU, or about 2 billion CFU, or about 1 billion CFU. In some embodiments, the amount of Streptococcus thermophilus bacterium is about 5 billion CFU for individuals aged 13+ and about 1 billion for children up to the age of about 13.

[0075] Any or all of the Lactobacillus helveticus, Lactobacillus plantarum, Bifidobacterium longum, and Streptococcus thermophilus may be employed in the form of live cells or dead cells. In some embodiments, one or more of the Lactobacillus helveticus, Bifidobacterium longum, and Streptococcus thermophilus are employed in the form of live cells or dead cells. In some embodiments, the Lactobacillus helveticus, Bifidobacterium longum, and Streptococcus thermophilus are employed in the form of live cells or dead cells.

[0076] The composition of the present disclosure further includes at least one plant-based, antioxidant-rich source of fiber. Examples thereof include, but are not limited to, all varieties ofDocket No. 0218-0012W01 berries having anthocyanin antioxidants such as blueberries, chokeberries, bilberries, or blackberries.

[0077] In some embodiments, the plant-based, antioxidant-rich source of fiber is employed in a therapeutically effective amount which can include from about 100 mg to about 5000 mg, including from about 400 mg to about 2000 mg, or from about 100 to about 500 mg, or about 800 mg, or about 200 mg, all weights based on the total dry actives weight of the composition.

[0078] According to one embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema comprising: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (iii) Bifidobacterium longum, and (iv) Streptococcus thermophilis,' and (b) at least one plant-based, antioxidant-rich source of fiber.

[0079] According to one embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema comprising a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) from about 0.1 to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 to about 20 billion CFU of Lactobacillus plantarum, (iii) up to about 20 billion CFU of Bifidobacterium longum, and (iv) from about 1 to about 20 billion CFU of Streptococcus thermophilus, and (b) from about 100 to about 5000 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition, and wherein the composition is administered orally. In some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0080] According to yet another embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema comprising a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) 0.1 to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 1 to about 10 billion CFU of Streptococcus thermophilus,- and (b) from about 100 to about 500 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition, and wherein theDocket No. 0218-0012W01 composition is administered orally. Tn some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0081] According to a particular embodiment of the present disclosure, the composition contains a therapeutically effective amount of: (a) a probiotic blend of bacterial components containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 5 billion CFU of Lactobacillus plantarum , (iii) about 2.4 CFU of Bifidobacterium longum, and (iv) about 2 billion CFU of Streptococcus thermophilus; and (b) about 200 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition, and wherein the composition is administered orally. In some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0082] According to another embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema, the composition comprising: (a) from about 1 mg to about 100 mg of a probiotic blend containing at least: (i) from about 0.2 billion to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 billion to about 10 billion CFU of Bifidobacterium longum, and (iv) from about 0.2 billion to about 20 billion CFU of Streptococcus thermophilus; and (b) from about 100 mg to about 5000 mg of at least one plant-based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.

[0083] According to a further embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema, the composition comprising: (a) from about 5 mg to about 50 mg of a probiotic blend containing at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 billion to about 10 billion CFU of Streptococcus thermophilus; and (b) from about 400 mg to about 2000 mg of at least one plantbased, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.

[0084] According to a further embodiment of the present disclosure, there is provided a composition for ameliorating and managing symptoms associated with eczema, the compositionDocket No. 0218-0012W01 comprising: (a) from about 5 mg to about 50 mg of a probiotic blend containing at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 billion to about 10 billion CFU of Streptococcus thermophilus; and (b) from about 100 mg to about 1000 mg of at least one plantbased, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.

[0085] According to yet another embodiment of the present disclosure, the composition contains: (a) about 50 mg of a probiotic blend containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and (b) about 200 mg of blueberry powder, all weights based on the total dry weight of the composition.

[0086] According to yet another embodiment of the present disclosure, the composition contains: (a) about 50 mg of a probiotic blend containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and (b) about 800 mg of blueberry powder, all weights based on the total dry weight of the composition.

[0087] Additional probiotic strains which may also be employed in the compositions of the present disclosure include, but are not limited to: 7. acidophilus DCC3302, L. acidophilus 1-92, L. rhamnosus, L. paracasei, L. salivarius LS01, Limosilactobacillus reuteri DSM 17938, L. johnsonii, B. bifidum, B. breve BR03, and B. lactis.

[0088] The compositions of the present disclosure can also include at least one vitamin chosen from B3, B5, B6, B7, B9, and B 12. A deficiency in any one or more of these B vitamins can trigger various digestive tract issues such as diarrhea, colitis, digestive problems, and the breakdown of intestinal tight junctions within the gut’s mucosal barrier.

[0089] Regarding B12, a deficiency in this vitamin has been directly correlated with elevated homocysteine levels. High homocysteine can indicate increased inflammation, which may further contribute to the weakening of the intestinal barrier, exacerbating leaky gut issues.Docket No. 0218-0012W01

[0090] More particularly, a deficiency in vitamin B12 has been associated with leaky gut in eczema sufferers due to increased intestinal permeability. Vitamin B 12 deficiency has also been associated with autoimmune conditions due to disruptions in the body’s immune system.

[0091] The composition may include one or more B vitamins selected from B3, B5, B6, B7, B9, and B12. In some embodiments, the B vitamin is employed in an amount of from about 100 to about 5000 mg, including from about 100 to about 500 mg, and particularly about 200 mg, all weights based on the total dry actives weight of the composition. In some embodiments, the composition includes vitamin B 12. The vitamin B12 component may be included at a dose ranging from about 2.4 micrograms (mcg) up to 1000 micrograms (1 mg) per dose, depending on the formulation goal. These amounts are based on the total dry active weight of the composition. In some embodiments, the composition includes vitamin B12 and one or more B vitamins selected from vitamin B3, B5, B6, B7, and B9. In some embodiments, the composition includes vitamin B 12 and vitamin B6. Exemplary amounts of B vitamins that may be included in the composition are as described in the following Table 1.Table 1.Docket No. 0218-0012W01

[0092] In some embodiments, the composition includes about 2.4 mcg to about 1 mg vitamin B12, and about 1.3 to about 100 mg vitamin B6.

[0093] Since the compositions of the present disclosure are, in some embodiments, meant to be orally administered, a carrier suitable for ingestion should be used. If the composition is employed in dry form, such as in the case of an enterically coated capsule, the formulation agents and excipients used to make the capsules are well known in the field. The rationale behind the use of compositions in an encapsulated form is to significantly improve their survival time as they travel through the body. In such a case, the use of certain types of capsules can retard or prevent the degradation of the microorganism in the gastrointestinal tract. It should be noted, however, that the compositions may be employed in any type of galenic form typically used for oral administration.

[0094] Besides their direct and independent benefits, the ingredients of the dietary supplements of this disclosure are believed to work together synergistically in a manner that powerfully enhances each ingredient's level of efficacy, thereby further promoting their beneficial eczema symptom ameliorating effect. Without intending to be bound by theory, the inventors believe that the disclosed probiotic blend, in combination with prebiotic in the form of a plant-based, antioxidant rich source of fiber, helps to facilitate gut microbiome symbiosis / balance, enhanced support of the body's immune system, mitigation of inflammatory mediators, and the restoration of skin barrier integrity, all of which is facilitated via the gut-skin-axis.

[0095] According to yet another embodiment, the present disclosure is also directed to a method of treating eczema-prone skin, comprising orally administering to a human subject in need thereof, a therapeutically effective oral dose of the above-disclosed compositions.

[0096] In some embodiments, the method comprises orally administering a composition comprising: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (iii) Bifidobacterium longum, and (iv) Streptococcus thermophilis, and (b) at least one plant-based, antioxidant-rich source of fiber.Docket No. 0218-0012W01

[0097] In some embodiments, the method comprises orally administering a composition comprising: (a) a probiotic blend of bacterial components containing at least: (i) from about 0.1 to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 to about 20 billion CFU of Lactobacillus plantarum, (iii) up to about 20 billion CFU of Bifidobacterium longum, and (iv) from about 1 to about 20 billion CFU of Streptococcus thermophilus,' and (b) from about 100 to about 5000 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition. In some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0098] In some embodiments, the method comprises orally administering a composition comprising: (a) a probiotic blend of bacterial components containing at least: (i) 0.1 to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 1 to about 10 billion CFU of Streptococcus thermophilus, and (b) from about 100 to about 500 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the compositionV In some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0099] In some embodiments, the method comprises orally administering a composition comprising: (a) a probiotic blend of bacterial components containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 5 billion CFU of Lactobacillus plantarum, (iii) about 2.4 CFU of Bifidobacterium longum, and (iv) about 2 billion CFU of Streptococcus thermophilus, and (b) about 200 mg of a plant based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition. In some embodiments, the probiotic blend is about 1 mg to about 100 mg, or about 5 mg to about 50 mg, or about 50 mg.

[0100] In some embodiments, the method comprises orally administering a composition comprising: (a) from about 1 mg to about 100 mg of a probiotic blend containing at least: (i) from about 0.2 billion to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 billion to about 10 billion CFU of Bifidobacterium longum, and (iv) from about 0.2 billion to about 20 billion CFU of Streptococciis thermophilus; and (b) from about 100 mg to about 5000 mg of at least one plant-based, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.Docket No. 0218-0012W01

[0101] In some embodiments, the method comprises orally administering a composition comprising: (a) from about 5 mg to about 50 mg of a probiotic blend containing at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 billion to about 10 billion CFU of Streptococcus thermophilus; and (b) from about 400 mg to about 2000 mg of at least one plantbased, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.

[0102] In some embodiments, the method comprises orally administering a composition comprising: (a) from about 5 mg to about 50 mg of a probiotic blend containing at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 billion to about 10 billion CFU of Streptococcus thermophilus; and (b) from about 100 mg to about 1000 mg of at least one plantbased, antioxidant-rich source of fiber, all weights based on the total dry weight of the composition.

[0103] In some embodiments, the method comprises orally administering a composition comprising: (a) about 50 mg of a probiotic blend containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and (b) about 200 mg of blueberry powder, all weights based on the total dry weight of the composition.

[0104] In some embodiments, the method comprises orally administering a composition comprising: (a) about 50 mg of a probiotic blend containing at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and (b) about 800 mg of blueberry powder, all weights based on the total dry weight of the composition.

[0105] In some embodiments, the composition administered by the method described herein further comprises one or more B vitamins selected from B3, B5, B6, B7, B9, and B 12. In someDocket No. 0218-0012W01 embodiments, the B vitamin is employed in an amount of from about 100 to about 5000 mg, including from about 100 to about 500 mg, and particularly about 200 mg, all weights based on the total dry actives weight of the composition. Exemplary amounts of B vitamins are described in Table 1. In some embodiments, the composition includes vitamin Bl 2. In some embodiments, the composition includes vitamin B 12 and one or more B vitamins selected from vitamin B3, B5, B6, B7, and B9. In some embodiments, the composition includes vitamin B 12 and vitamin B6. In some embodiments, the composition includes about 2.4 mcg to about 1 mg vitamin B 12, and about 1.3 to about 100 mg vitamin B6.References• Atopic Dermatitis: Inside Out Or Outside in, Lawrence S. Chan and Vivian Y. Shi, Elsevier 2022. ISBN 978-0-323-84744-5, doi: 10.1016 / C2020-0-03798-9.• Leung DY, "Role of IgE in atopic dermatitis," Curr Opin Immunol. 5(6):956-62 (1993). doi : 10.1016 / 0952-7915(93)90112-6.• Cristofori et al., "Anti-Inflammatory and Immunomodulatory Effects of Probiotics in Gut Inflammation: A Door to the Body," Front Immunol. 12:578386 (2021). doi: 10.3389 / fimmu.202L 578386. PMID: 33717063; PMCID: PMC7953067.• Makrgeorgou et al., "Probiotics for treating eczema," Cochrane Database Syst Rev. ll(ll):CD006135 (2018). doi: 10.1002 / 14651858.CD006135.pub3.• Zmora et al., "Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features," Cell 174(6): 1388-1405. e21 (2018).• Miraglia Del Giudice et al., "Probiotics and Atopic dermatitis. A new strategy in Atopic Dermatitis," Digest Liver Dis. 34 Suppl.21 :S68-71 (2002).• Rook GAW and Brunet LR, "Microbes, immunoregulation, and the gut," Gut 54:317-320 (2005).• isappscience.org / postbiotics-debate-continues-and-the-isapp-definition-gains-support• Nataraj et al., "Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods," Microb Cell Fact 19: 168 (2020). doi: 10.1186 / sl2934-020-01426-w.Docket No. 0218-0012W01• Pique et al., "Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview," Int J Mol Sci. 20(10):2534 (2019). doi: 10.3390 / ijms20102534. PMID: 31126033; PMCID: PMC6566317.EXAMPLES

[0106] The following examples as set forth herein are intended for illustrative purposes only and are not intended to limit the scope of the disclosure in any way, as many variations thereof are possible without departing from the spirit and scope of the disclosure. In the example, all concentrations are listed as dry weight, unless otherwise specified.Example 1

[0107] The results of an open label study with 30 participants using the probiotic of Example 1 are shown in FIG. 1. In FIG. 1, "SCORAD" stands for SCORing Atopic Dermatitis, a well- recognized, standard clinical assessment tool used to assess the severity of eczema (atopic dermatitis). It is calculated using a formula that considers: Extent (A) = percentage of body surface area affected by eczema; Intensity (B) = based on clinical signs of the disease (redness, swelling, oozing, crusting, scratching and dryness; and Subjective symptoms (C) = patient reported score for symptoms.

[0108] At day 56 of the study:100% of all subjects showed an average of 93% improvement in SCORAD;97% of subjects showed an average of 92% reduction in itching; and 97% of subjects showed an average of 88% reduction in insomnia.

[0109] Despite the relatively small size of the study, the magnitude of the results are clear, compelling, and astonishingly surprising.

Claims

Docket No. 0218-0012W01What is claimed is:

1. A composition for ameliorating and managing symptoms associated with eczema comprising: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (iii) Bifidobacterium longum, and (iv) Streptococcus thermophilus,' and (b) at least one plant-based, antioxidant-rich source of fiber.

2. The composition of claim 1, wherein (a) is employed in an amount of from about 1 mg to about 100 mg and contains at least: (i) from about 0.2 billion to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 billion to about 10 billion CFU of Bifidobacterium longum, and (iv) from about 0.2 billion to about 20 billion CFU of Streptococcus thermophilus; and wherein (b) is employed in an amount of from about 100 mg to about 5000 mg, all weights based on the total dry weight of the composition.

3. The composition of claim 1 or 2, wherein (a) is employed in an amount of from about 5 mg to about 50 mg and contains at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 to about 10 billion CFU of Streptococcus thermophilus; and wherein (b) is employed in an amount of from about 400 mg to about 2000 mg, all weights based on the total dry weight of the composition.

4. The composition of any one of claims 1 to 3, wherein (a) is employed in an amount of about 50 mg and contains at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and wherein (b) comprises about 800 mg of blueberry powder, all weights based on the total dry weight of the composition.

5. The composition of any one of claims 1 to 3, wherein (a) is employed in an amount of about 50 mg and contains at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii)Docket No. 0218-0012W01 about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and wherein (b) comprises about 200 mg of blueberry powder, all weights based on the total dry weight of the composition.

6. The composition of any one of claims 1 to 5, further comprising at least one B vitamin selected from B3, B5, B6, B7, B9, and B12.

7. The composition of claim 6, wherein the composition comprises vitamin B6 and vitamin B12.

8. A method of ameliorating symptoms associated with eczema-prone skin comprising orally administering a composition comprising: (a) a probiotic blend of bacterial components containing at least: (i) Lactobacillus helveticus, (ii) Lactobacillus plantarum, (iii) Bifidobacterium longum, and (iv) Streptococcus thermophilus and (b) at least one plant-based, antioxidant-rich source of fiber.

9. The method of claim 8, wherein (a) is employed in an amount of from about 1 mg to about 100 mg and contains at least: (i) from about 0.2 billion to about 20 billion CFU of Lactobacillus helveticus, (ii) from about 0.1 billion to about 10 billion CFU of Lactobacillus plantarum, (iii) from about 0.1 billion to about 10 billion CFU of Bifidobacterium longum, and (iv) from about 0.2 billion to about 20 billion CFU of Streptococcus thermophilus; and wherein (b) is employed in an amount of from about 100 mg to about 5000 mg, all weights based on the total dry weight of the composition.

10. The method of claim 8 or 9, wherein (a) is employed in an amount of from about 5 mg to about 50 mg and contains at least: (i) from about 0.5 billion to about 10 billion CFU of Lactobacillus helveticus, (ii) from about 0.2 billion to about 2 billion CFU of Lactobacillus plantarum, (iii) from about 0.2 billion to about 5 billion CFU of Bifidobacterium longum, and (iv) from about 0.5 billion to about 10 billion CFU of Streptococcus thermophilus; and wherein (b) is employed in an amount of from about 400 mg to about 2000 mg, all weights based on the total dry weight of the composition.Docket No. 0218-0012W0111 . The method of any one of claims 8 to 10, wherein (a) is employed in an amount of about 50 mg and contains at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and wherein (b) comprises about 800 mg of blueberry powder, all weights based on the total dry weight of the composition.

12. The method of any one of claims 8 to 10, wherein (a) is employed in an amount of about 50 mg and contains at least: (i) about 5 billion CFU of Lactobacillus helveticus, (ii) about 1 billion CFU of Lactobacillus plantarum, (iii) about 2 billion CFU of Bifidobacterium longum, and (iv) about 5 billion CFU of Streptococcus thermophilus; and wherein (b) comprises about 200 mg of blueberry powder, all weights based on the total dry weight of the composition.

13. The method of any one of claims 8 to 12, wherein the composition further comprises at least one B vitamin selected from B3, B5, B6, B7, B9, and B 12.

14. The method of claim 13, wherein the composition comprises vitamin B6 and vitamin B12.

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