Compositions and uses thereof

Abstract

The present invention relates to a composition for use in the treatment and / or prevention of dry and / or sensitive skin conditions in a subject. The composition comprises at least two bacterial species that reduce levels of interleukin-17 and / or interleukin-23 in a subject, and / or increase levels of interleukin-10 in a subject, and / or improve gut barrier function in a subject. The at least two bacterial species may comprise Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri, and / or Lactococcus lactis.

Description

[Technical field]

[0001] Technical Field The present invention relates to compositions and uses of said compositions in the treatment or prevention of dry or sensitive skin conditions, such as psoriasis. [Background technology]

[0002] Background to the invention Humans live in constant contact with many microorganisms. The intestine is by far the most colonized, and the gut microbiota has been shown to play multiple roles in normal physiology, including nutrient sequestration and the generation of normal immune responses. Furthermore, the gut microbiota has increasingly been shown to play a role in disease and the treatment and management of disease.

[0003] Among the normal gut microbiota, so-called probiotic bacteria exist. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. The concept that probiotics are beneficial for gut health has been extensively investigated and studies have demonstrated that probiotics can potentially improve gut function through several mechanisms, including improving epithelial barrier function and modulating immune responses. There is also evidence that probiotics can prevent gut colonization by pathogens, for example, by downregulating virulence factors or inhibiting pathogen adhesion to the epithelium.

[0004] Ingestion of probiotic bacteria has been shown to prevent or treat gastrointestinal disorders such as antibiotic-associated diarrhea and inflammatory bowel disease. However, in general, relatively little information is available regarding the molecular mechanisms that mediate the observed effects of probiotics.

[0005] Because probiotics may have a positive effect on the gut, their potential effects on other organs, such as the oral cavity and urogenital tract, are also beginning to be explored, and topical application of probiotics to the skin has been investigated in a limited number of studies. Compelling evidence suggests that gastrointestinal (GI) disorders are associated with several inflammatory skin diseases, such as rosacea, psoriasis, and atopic dermatitis. Patients with psoriasis are at increased risk of developing enteritis, and 7-11% of patients with inflammatory bowel disease are diagnosed with psoriasis. Studies have also shown that individuals with psoriasis and atopic dermatitis have a lower diversity of the gut microbiome, which may be related to a reduced ability of the gut to regulate immune responses and local inflammatory responses. Alterations in the gut microbiome have also been linked to immune system reactivity and disturbances in skin homeostasis and inflammatory skin diseases. In addition, other mechanisms involved in the gut-skin axis have been demonstrated, including the ability of the gut microbiota to synthesize molecules that can travel to the bloodstream and accumulate in the skin, which may affect skin condition, and the effect of the gut microbiota on mood. Although these mechanisms have yet to be fully elucidated, there is compelling evidence demonstrating connections between the nervous, immune and secretory systems, as well as a relationship between the gut microbiome and skin health that involves environmental factors.

[0006] Psoriasis is a complex chronic inflammatory condition that appears as scaly, erythematous and painful, itchy, unsightly dry skin plaques. These lesions are usually found on the hands, feet and scalp. Psoriasis has a profound mental and social impact, leading to isolation, affecting employment and causing anxiety and depression. It is also associated with co-morbidities such as inflammatory bowel disease, cardiovascular disease and diabetes. The severity of psoriasis varies from 1-2% skin plaques (mild) to covering almost the entire body (severe) and is classified into the following types: plaque, guttate, inverse, pustular and erythrodermic. Plaque psoriasis is the most common form of psoriasis, accounting for approximately 85-90% of cases. This type of psoriasis typically appears as red patches with white or silvery scales on the top, most commonly seen on the elbows, knees and scalp. The prevalence of psoriasis in the UK is 2-4% and the economic impact of psoriasis exceeds £1 billion per year.

[0007] Although the processes involved in the development of psoriasis are not fully understood, psoriasis has an immune component and is now often thought to be an autoimmune condition in which the immune system attacks healthy skin cells. Furthermore, as mentioned above, psoriasis patients have a low diversity of the gut microbiome and "leaky gut" has been observed in people with psoriasis. In mouse models of psoriasis, modulation of the gut microbiome influences the skin. It has not been determined how the microbiome exerts its effect on the skin, but it is thought that it may be related to the modulatory effect of probiotics on systemic immunity.

[0008] Many treatment options are available for psoriasis, but there is no cure. Patient care is under the supervision of a dermatologist, but many also purchase supportive products to reduce the severity and extent of disease. Although therapeutic drugs are effective, few patients have good disease control, and there is significant treatment dissatisfaction with drugs that have a significant side effect profile.

[0009] Due to the suspected immune origin of psoriasis, many treatments have focused on the use of immunosuppressants, both topical and systemic. In milder cases of the condition, topical treatments such as vitamin D or corticosteroids are often used. In more severe cases, phototherapy or systemic treatments are utilized. Patients with psoriasis often exhibit elevated levels of inflammatory markers such as interleukins, particularly interleukin-17 (IL-17) and interleukin-23 (IL-23), and more recently there has been a focus on modulating the levels of such inflammatory markers, or developing therapeutic approaches that affect molecular pathways related to immune pathways.

[0010] Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory skin condition. AD is the most common form of eczema, currently adversely affecting approximately 20% of the pediatric population in the Western world. AD causes itchy, red, dry and cracked skin. Scratching aggravates the condition and increases the risk of skin infections in affected individuals. Once the skin barrier is breached, irritants such as soaps and detergents dry out the skin, further aggravating the weakened skin barrier. Foods, microbes and other allergens can also penetrate the upper layers of the skin, potentially triggering an allergic reaction. Some people have only small patches of dry skin, while others have red, inflamed skin all over their body.

[0011] Treatments used to control symptoms and manage AD include self-care techniques such as reducing scratching and avoiding triggers, emollients (moisturizers), and topical corticosteroids used to reduce swelling, redness, and itching during flare-ups.

[0012] Topical corticosteroids may cause a mild tingling sensation upon application and, rarely, may cause skin thinning, skin thickening, stretch marks, changes in skin color, acne, and increased hair growth. Less common but more serious side effects of steroids include glaucoma, cataracts, small pink bumps on the skin, red, pus-filled hair follicles, adrenal suppression, and topical steroid dependency / withdrawal. For particularly severe flare-ups, corticosteroid tablets may be prescribed, but treatment periods longer than 7 days are generally avoided due to the potential risk of serious side effects.

[0013] Alternative nonsteroidal AD treatments include topical calcineurin inhibitors such as pimecrolimus and tacrolimus, which suppress the immune system, phototherapy, bandages or wet wraps, immunosuppressant tablets, and alitretinoin, which treats severe eczema affecting the hands of adults. However, there are concerns that calcineurin inhibitors may increase the risk of skin cancer or lymphoma.

[0014] Ichthyosis is a condition that causes widespread, persistent, thick, dry, scaly skin. There are more than 20 different types of ichthyosis, which vary in severity and appearance. The most common type of ichthyosis, ichthyosis vulgaris, causes relatively mild symptoms. However, the most severe types of ichthyosis can be life-threatening.

[0015] Treatment for ichthyosis typically involves topical emollients or creams and exfoliation to remove the scale. In more severe cases, oral retinoids may be prescribed to reduce skin cell production. However, treatment options are limited.

[0016] It is an object of the present invention to avoid or alleviate one or more of the above problems and / or to provide an improved treatment for dry and / or sensitive skin conditions such as psoriasis, atopic dermatitis and ichthyosis. Summary of the Invention

[0017] Summary of the Invention The present invention relates to compositions and uses of compositions in the treatment or prevention of dry and / or sensitive skin conditions. The present invention is based in part on research by the inventors showing that certain probiotic bacterial species can reduce the expression of interleukin-17 (IL-17) and interleukin-23 (IL-23), increase the expression of interleukin-10 (IL-10), and improve intestinal barrier function. The inventors have shown that oral use of such probiotic bacterial species, particularly a blended population of such probiotic bacterial species, results in improved skin health.

[0018] In a first aspect of the present invention there is provided a composition for use in the treatment and / or prevention of a dry and / or sensitive skin condition in a subject, the composition comprising at least two bacterial species to reduce levels of interleukin-17 and / or interleukin-23 in the subject, and / or to increase levels of interleukin-10 in the subject, and / or to improve intestinal barrier function in a subject.

[0019] In a second aspect of the present invention, there is provided a composition comprising at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23, and / or increases levels of interleukin-10, and / or improves intestinal barrier function.

[0020] The bacterial species may be a probiotic bacterial species. Thus, the composition of the present invention may comprise at least two probiotic bacterial species, and therefore can be described as a probiotic composition. Probiotic bacteria are defined by the World Health Organization as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. Thus, as will be understood by those skilled in the art, the "probiotic composition" of the present invention is a composition that comprises at least two probiotic bacterial species that, when applied to a subject, provides a beneficial effect to the subject.

[0021] The inventors have found that managing inflammatory responses in individuals with dry or sensitive skin conditions can treat these conditions. Many such conditions, such as psoriasis, are associated with uncontrolled or excessive inflammatory responses, and reducing this inflammatory response to more normal levels (i.e., levels seen in subjects not affected by such conditions) can manage the condition. By using a blend of bacterial species (rather than a single strain approach), the inventors have developed a composition that can take advantage of the use of a blended population of probiotics that target different physiological aspects of skin diseases.

[0022] As used herein, the phrase "reducing the levels of interleukins" means that the levels of interleukins in a subject are reduced compared to the levels prior to treatment with a bacterial species. Reducing the levels of interleukins (e.g., IL-17, IL-23) in a subject with a dry or sensitive skin condition, such as psoriasis, reduces the levels of these interleukins to the levels of interleukins observed in subjects without said dry or sensitive skin condition.

[0023] As used herein, the phrase "increasing the levels of interleukins" means that the levels of interleukins in a subject are increased compared to the levels prior to treatment with a bacterial species. Increasing the levels of interleukins (e.g., IL-10) in a subject having a dry or sensitive skin condition, such as psoriasis, increases the levels of these interleukins to at least the levels of interleukins observed in subjects without said dry or sensitive skin condition.

[0024] As will be appreciated by those skilled in the art, there are a variety of ways in which the levels of interleukins can be measured, for example, by testing the concentration of said interleukins in the blood using an enzyme-linked immunosorbent assay (ELISA).

[0025] As mentioned above, dry and sensitive skin conditions, such as psoriasis, have been found to be associated with altered microbiomes and leaky gut. As used herein, the phrase "improve gut barrier function" means that the gut's function of preventing the passage of pathogens and other harmful molecules across the gut is improved compared to its function before treatment with the bacterial species. The gut function is improved to be more comparable to the gut function of subjects without said dry or sensitive skin condition. Those skilled in the art will understand that gut function can be tested, for example, by measuring the ratio of mannitol:lactulose in urine after oral ingestion of sugars such as mannitol and lactulose.

[0026] As will be appreciated by those of skill in the art, references to bacterial species in a composition that reduce interleukin levels and / or increase interleukin levels and / or improve intestinal function are referring to interleukin levels and / or intestinal function in a subject to which the composition is administered.

[0027] In embodiments, the bacterial species may be selected from the group consisting of Lactobacillus sp., Bifidobacterium sp., Lactococcus sp., Streptococcus sp., and / or combinations thereof. In embodiments, the bacterial species may be selected from the group consisting of Lactobacillus sp., Bifidobacterium sp., Lactococcus sp., Streptococcus sp., and / or combinations thereof.

[0028] Bacterial species of the present invention include, for example, Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri, Lactococcus lactis / Lactococcus cremoris, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus paracasei, Lactobacillus The bacterium may be selected from Lactobacillus paracasei, Lactobacillus acidophilus and Bifidobacterium breve.

[0029] In an embodiment of the invention, the composition comprises at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis.

[0030] Lactococcus lactis may also be known as Lactococcus cremoris. Thus, in an embodiment, the composition comprises at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus cremoris.

[0031] Thus, the present invention provides a composition for use in the treatment and / or prevention of a dry and / or sensitive skin condition in a subject, the composition comprising at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0032] The present invention also provides compositions comprising at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0033] Bifidobacterium animalis (B. animalis) is a gram-positive, anaerobic, rod-shaped bacterium found in the gastrointestinal tract of many mammals, including humans. The scientific classification of B. animalis is: Kingdom: Bacteria; Phylum: Firmicutes; Class: Actinobacteria; Order: Bifidobacteria; Family: Bifidobacteriaceae; Genus: Bifidobacterium; Species: Bifidobacterium animalis. B. animalis is commonly used as a probiotic.

[0034] Lactobacillus brevis (L. brevis) is a gram-positive, rod-shaped, lactic acid bacterium that is commonly found, for example, in dairy products. The scientific classification of L. brevis is: Kingdom: Bacteria; Phylum: Gram-positive Bacteria; Class: Bacilli; Order: Lactobacillales; Family: Lactobacilliaceae; Genus: Lactobacillus; Species: Lactobacillus brevis.

[0035] Lactobacillus reuteri (L. reuteri) is a gram-positive, rod-shaped, anaerobic bacterium found in the gastrointestinal tract of many mammals, including humans. The scientific classification of L. reuteri is: Kingdom: Bacteria; Phylum: Gram-positive Bacteria; Class: Bacilli; Order: Lactobacillales; Family: Lactobacilliaceae; Genus: Lactobacillus; Species: Lactobacillus reuteri.

[0036] Lactococcus lactis (L. lactis) is a gram-positive lactic acid bacterium. The scientific classification of L. lactis is: Kingdom: Bacteria; Phylum: Gram-positive bacteria; Class: Bacilli; Order: Lactobacillales; Family: Streptococcaceae; Genus: Lactococcus; Species: Lactococcus lactis. L. lactis can also be Lc. cremoris.

[0037] In an embodiment of the invention, the composition comprises at least two of B. animalis, L. brevis, L. reuteri and L. lactis / Lc. cremoris.

[0038] In an embodiment of the present invention, the composition may comprise two of the bacterial species listed above. For example, in an embodiment, the composition may comprise B. animalis and L. brevis. In an embodiment, the composition may comprise B. animalis and L. reuteri. In an embodiment, the composition may comprise B. animalis and L. lactis / Lc. cremoris. In an embodiment, the composition may comprise L. brevis and L. reuteri. In an embodiment, the composition may comprise L. brevis and L. lactis / Lc. cremoris. In an embodiment, the composition may comprise L. reuteri and L. lactis / Lc. cremoris.

[0039] In an embodiment of the present invention, the composition may comprise three of the bacterial species listed above. For example, in an embodiment, the composition may comprise B. animalis, L. brevis and L. reuteri. In an embodiment, the composition may comprise B. animalis, L. brevis and L. lactis / Lc. cremoris. In an embodiment, the composition may comprise B. animalis, L. reuteri and L. lactis / Lc. cremoris. In an embodiment, the composition may comprise L. brevis, L. reuteri and L. lactis / Lc. cremoris. In an embodiment, the composition may comprise L. brevis, L. reuteri and L. lactis / Lc. cremoris.

[0040] In a preferred embodiment of the invention, the composition may comprise B. animalis, L. brevis, L. reuteri and L. lactis / Lc. cremoris.

[0041] In an embodiment of the invention, the bacterial species present in the composition may consist of one of the above combinations, for example B. animalis, L. brevis, L. reuteri and L. lactis / Lc. cremoris.

[0042] The inventors have surprisingly found that these bacterial species may be particularly useful in treating dry and / or sensitive skin conditions, as they are effective in reducing the levels of IL-17 and / or IL-23, and / or increasing the levels of IL-10, and / or improving the gut barrier. The inventors have further shown that this combination of bacterial species results in improved skin health. By utilizing this blend of bacterial species, the inventors have developed a composition that can take advantage of using a blended population of probiotics that target different physiological aspects of skin disease (e.g., immune and gut-related aspects). Without wishing to be bound by theory, the inventors hypothesize that by reducing the levels of these pro-inflammatory interleukins (IL-17 and / or IL-23) and / or increasing the levels of the anti-inflammatory interleukin IL-10, and / or improving the gut barrier, improvement of dry and sensitive skin conditions, particularly psoriasis, may be achieved.

[0043] In embodiments where the composition comprises B. animalis, the B. animalis may comprise, for example, Bifidobacterium animalis subsp. lactis. In embodiments, the B. animalis may comprise, for example, Bifidobacterium animalis subsp. lactis BB-12® and / or strains derived therefrom. In embodiments where the composition comprises B. animalis, the B. animalis may comprise B. animalis W53, commercially available from Winclove Probiotics BV, and / or strains derived therefrom.

[0044] In embodiments in which the composition comprises L. brevis, the L. brevis may comprise, for example, L. brevis LP9 and / or strains derived therefrom. In embodiments in which the composition comprises L. brevis, the L. brevis may comprise L. brevis W63, available commercially from Winclove Probiotics BV, and / or strains derived therefrom.

[0045] In embodiments in which the composition comprises L. reuteri, the L. reuteri may comprise, for example, L. reuteri FN041 and / or strains derived therefrom. In embodiments in which the composition comprises L. reuteri, the L. reuteri may comprise L. reuteri W192 and / or strains derived therefrom, which are commercially available from Winclove Probiotics BV.

[0046] In embodiments in which the composition comprises L. lactis, the L. lactis may, for example, comprise L. lactis NZ9000 and / or strains derived therefrom. In embodiments in which the composition comprises L. lactis, the L. lactis may, for example, comprise Lc. cremoris W224, available commercially from Winclove Probiotics BV, and / or strains derived therefrom.

[0047] As used herein, the phrase "strain derived therefrom" refers to a strain that has a genomic mutation (e.g., insertion, deletion, substitution) compared to the original strain, but retains the ability to treat or prevent a skin condition by reducing the levels of interleukin-17 and / or interleukin-23 in a subject, and / or increasing the levels of interleukin-10 in a subject, and / or improving the intestinal barrier function in a subject. A person skilled in the art will know how such a strain can be derived using mutagenesis methods well known in the art, such as, for example, site-directed mutagenesis or random mutagenesis.

[0048] In embodiments of the invention in which the composition comprises at least two of Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and L. lactis / Lc. cremoris, the composition may comprise additional bacterial species, e.g., probiotic bacterial species. Suitable probiotic bacterial species include, for example, bacterial species selected from the group consisting of Lactobacillus sp., Bifidobacterium sp., Lactococcus sp., Streptococcus sp., and combinations thereof. In particular, bacterial species particularly suitable for inclusion in the compositions of the present invention include, for example, Lactobacillus acidophilus (e.g., strain LA5), Lactobacillus casei (e.g., strain DN001), Lactobacillus plantarum (e.g., strain HY7714 / K8), Lactobacillus pentosus, Lactobacillus paracsei (e.g., strain CS3), Lactobacillus acidophilus (e.g., strain IDCC3302), Bifidobacterium infantis (e.g., strain 35624), and Bifidobacterium breve (e.g., strain B3).

[0049] Preferably, the additional bacterial species is a bacterial species that reduces the level of IL-23 and / or IL-17.Preferably, the additional bacterial species is a bacterial species that increases the level of IL-10.Preferably, the bacterial species is a bacterial species that improves intestinal barrier function.As shown by the present inventors, the bacterial species that exhibit these activities are particularly suitable for treating dry or sensitive skin conditions.

[0050] The bacterial species present in the composition of the present invention are live bacterial species, i.e., alive and not killed or inactivated. However, it will be understood that the composition of the present invention, in addition to containing live probiotic bacteria, may further contain cellular components of said probiotic bacteria (e.g., cell wall components, cell membrane components, nucleic acids, proteins, etc.), metabolic products and / or molecules secreted by said bacteria.

[0051] The compositions of the present invention may be used to treat and / or prevent dry and / or sensitive skin conditions in a subject.

[0052] As used herein, the terms "treatment," "treat," or "treating" mean that the composition relieves or alleviates the signs or symptoms of a dry and / or sensitive skin condition, improves the clinical course of the condition, reduces the number or severity of exacerbations, or reduces other objective or subjective manifestations of the condition.

[0053] As used herein, the terms "prevention," "prevent" or "preventing" mean that the composition avoids the occurrence of a condition, particularly, for example, if the subject is predisposed to the condition.

[0054] Those skilled in the art will appreciate that the phrase "dry and / or sensitive skin condition" encompasses conditions in which a subject's skin becomes itchy, irritated, red, dry, cracked, and / or inflamed, including, for example, psoriasis, eczema, ichthyosis, dermatitis (e.g., contact dermatitis or atopic dermatitis), acne, rosacea, and Netherton syndrome.

[0055] In an embodiment of the invention, the composition is for use in the treatment and / or prevention of psoriasis, atopic dermatitis, contact dermatitis, eczema, ichthyosis, acne, rosacea or Netherton syndrome. In a preferred embodiment of the invention, the composition is for use in the treatment and / or prevention of psoriasis, atopic dermatitis, contact dermatitis, eczema or ichthyosis.

[0056] Use of the compositions of the present invention advantageously avoids the side effects seen with corticosteroids which are frequently prescribed for the treatment of such conditions.

[0057] In a preferred embodiment of the present invention, the composition is for use in the treatment and / or prevention of psoriasis.As mentioned above, psoriasis can be classified into the following types: plaque, guttate, inverse, pustular and erythrodermic.The composition of the present invention can be used for the treatment and / or prevention of any type of psoriasis.

[0058] The inventors have surprisingly found that the compositions of the present invention may be particularly effective in treating or preventing psoriasis, which is associated with elevated levels of inflammatory markers such as IL-17 and IL-23, altered microbiome and leaky gut. The inventors have shown that when subjects suffering from psoriasis are treated with the probiotic bacteria composition of the present invention, the skin condition is significantly improved. Without wishing to be bound by theory, the inventors hypothesize that the provision of the probiotic bacteria of the present invention reduces IL-17 and IL-23 inflammatory markers, and / or increases the levels of anti-inflammatory markers such as IL-10, and / or restores or improves gut function, thereby resulting in improved skin condition.

[0059] As used herein, the term "subject" is used to refer to any individual suffering from dry or sensitive skin conditions.In an embodiment of the present invention, the subject may be, for example, a human or an animal, such as a dog, cat, rabbit, bird, cow, sheep, goat, horse or pony.However, in a preferred embodiment, the subject is a mammal, preferably a human.

[0060] In the compositions of the present invention, the bacterial species present, e.g., Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and / or L. lactis / Lc. cremoris, are present in a therapeutically effective amount. One of skill in the art will appreciate that the term "therapeutically effective amount" is used herein to mean the amount of bacterial species necessary to provide a therapeutic or preventive effect on dry and / or sensitive skin conditions.

[0061] As will be appreciated by one of skill in the art, a therapeutically effective amount may vary based on the subject's characteristics, such as the subject's age, weight, and sex. A therapeutically effective amount may also vary based on the route of administration.

[0062] In an embodiment of the invention, the total concentration of probiotic bacterial species in the composition is 10 6 From 10 12 cfu / g. Preferably, the total concentration of probiotic bacterial species in the composition is 10 8 From 10 10 cfu / g. More preferably, the total concentration of probiotic bacterial species in the composition is approximately 10 9 cfu / g.

[0063] In an embodiment of the invention, a therapeutically effective amount of a bacterial species is 10 6 From 10 12 cfu / day. Preferably, the therapeutically effective amount of a bacterial species is from 10 8 From 10 10 cfu / day. More preferably, the therapeutically effective amount of a bacterial species is approximately 10 9 When referring to a therapeutically effective amount of a bacterial species herein, the total amount of the bacterial species is 10 6 From 10 12 cfu / day, 10 8 From 10 10 cfu / day, or approximately 10 9 This refers to the number of cfu / day.

[0064] In an embodiment of the invention, the total concentration of the bacterial species Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lc. cremoris in the composition is 10 6 From 10 12 Preferably, the total concentration of the bacterial species Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and L. lactis / Lc. cremoris in the composition is 10 8 From 10 10More preferably, the total concentration of the bacterial species Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and L. lactis / Lc. cremoris in the composition is approximately 10 9 cfu / g.

[0065] In an embodiment of the invention, a therapeutically effective amount of the bacterial species Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris is 10 6 From 10 12 cfu / g. Preferably, the therapeutically effective amount of a bacterial species is up to 10 8 From 10 10 cfu / g. More preferably, the therapeutically effective amount of a bacterial species is approximately 10 9 cfu / day. When referring to a therapeutically effective amount of a bacterial species herein, the total amount of the bacterial species is 10 6 From 10 12 cfu / day, 10 8 From 10 10 cfu / day, or approximately 10 9 This refers to the number of cfu / day.

[0066] The compositions of the present invention have been shown to be useful in treating or preventing dry or sensitive skin conditions, such as psoriasis.However, alternatively or in addition, the compositions of the present invention may be used in cosmetics.The compositions may be used in cosmetics to improve the appearance and / or texture of skin.For example, the compositions may result in smoother and / or softer skin, or skin with fewer blemishes, increased firmness, reduced dryness, reduced redness, reduced skin sensitivity or reduced itching.The inventors have surprisingly shown that subjects treated with the probiotic compositions of the present invention often show improved skin health, such as smoother, softer skin and fewer blemishes.

[0067] Those skilled in the art will understand that the composition of the present invention can be in any suitable form, such as, for example, solution, gel or powder.In an embodiment, the composition is formulated for oral administration to a subject.As will be understood by those skilled in the art, as used herein, "oral" means administered or ingested by mouth.

[0068] Formulations suitable for oral administration include liquids, solutions (e.g., aqueous, non-aqueous), suspensions (e.g., aqueous, non-aqueous), emulsions (e.g., oil-in-water, water-in-oil), elixirs, syrups, lozenges, tablets, granules, powders, capsules, cachets, pills, ampoules, and boluses. Alternatively, the composition may be in the form of a foodstuff or food additive. The composition may be in the form of a drinkable liquid, a spread and / or powder that can be mixed with a solid or liquid foodstuff. The composition may be used as a dietary supplement, for example, blended with a food / drink or consumed together with a food / drink.

[0069] The composition may be encapsulated. Encapsulation techniques will be apparent to those skilled in the art and the technique employed will be adapted to the required stability of the bacterial species during the digestive passage.

[0070] The bacterial species may be concentrated and / or freeze-dried. Advantageously, many probiotic bacteria exhibit excellent freeze-drying survival.

[0071] In an embodiment, the composition comprises a powder that can be mixed with a liquid, such as water. The powder may comprise freeze-dried bacterial species.

[0072] The composition of the present invention may further comprise one or more pharma- ceutically or cosmetically acceptable ingredients or excipients. Pharmaceutically acceptable ingredients are well known to those skilled in the art and include, but are not limited to, pharma- ceutically acceptable carriers, adjuvants, excipients, diluents, fillers, buffers, preservatives, antioxidants, lubricants, stabilizers, solubilizers, surfactants (e.g., wetting agents), masking agents, colorants, fragrances, and penetrants.

[0073] The composition may further comprise one or more other active agents, eg, other therapeutic and / or prophylactic agents.

[0074] In a further aspect of the present invention, there is provided a method for treating and / or preventing a dry and / or sensitive skin condition in a subject, the method comprising administering to the subject a composition comprising at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23 in the subject, and / or increases levels of interleukin-10 in the subject, and / or improves intestinal barrier function in the subject.

[0075] Details of the composition are given above in relation to the first and second aspects of the invention.

[0076] In an embodiment, the composition comprises at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0077] Accordingly, the present invention provides a method for treating and / or preventing dry and / or sensitive skin conditions in a subject, the method comprising administering to the subject a composition comprising at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0078] In an embodiment of the method of the present invention, the composition is orally administered to a subject.Accordingly, the present invention provides a method for treating and / or preventing dry and / or sensitive skin conditions in a subject, the method comprising orally administering to the subject a composition comprising at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0079] As will be appreciated by those of skill in the art, as used herein, "oral" means ingested or administered through the mouth.

[0080] In an embodiment of the present invention, the composition may be administered to a subject daily for one week or more, for example, daily for one week, daily for two weeks, daily for three weeks, daily for four weeks, daily for five weeks, daily for six weeks, daily for seven weeks, daily for eight weeks. In an embodiment of the present invention, the composition may be administered to a subject daily for one month or more, for example, daily for one month, two months, three months, four months, five months, six months. In an embodiment of the present invention, the composition may be administered daily for an extended period of time, for example, for one year or more. In an embodiment of the present invention, the composition may be administered to a subject twice or three times a day, daily for one week or more.

[0081] The composition may be administered to the subject at any time of the day, however, preferably, the composition is administered on an empty stomach.

[0082] The compositions may be administered alone or in combination with other treatments, either simultaneously or sequentially.

[0083] The invention also provides the use of a composition in the manufacture of a medicament for the treatment and / or prevention of dry and / or sensitive skin conditions, the composition comprising at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23, and / or increases levels of interleukin-10, and / or improves intestinal barrier function.

[0084] In an embodiment, the composition comprises at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0085] Thus, the present invention provides the use of a composition in the manufacture of a medicament for the treatment and / or prevention of dry and / or sensitive skin conditions, the composition comprising at least two of the following bacterial species: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

[0086] Details of the composition are given above in relation to the first and second aspects of the invention.

[0087] In a further aspect of the present invention there is provided the use of a composition in the manufacture of a cosmetic composition for use in improving the appearance and / or texture of the skin, the composition comprising at least two bacterial species which reduce levels of interleukin-17 and / or interleukin-23 and / or increase levels of interleukin-10 and / or improve intestinal barrier function.

[0088] Use of the composition of the present invention for cosmetically improving the appearance and / or texture of skin is also provided.For example, the composition may result in smoother and / or softer skin, or skin with fewer blemishes, increased firmness, reduced flakiness, reduced redness, reduced skin sensitivity or reduced itching.

[0089] Details of the composition are given above in relation to the first and second aspects of the invention.

[0090] The embodiments described and illustrated are to be considered as exemplary and not restrictive in nature, it being understood that only the preferred embodiments have been shown and described, and that it is desired to protect all changes and modifications that come within the scope of the invention as defined in the claims.

[0091] Any features described herein may be used individually or in combination with one another, where appropriate, particularly in such combinations as are described in the appended claims. Any features for each aspect or exemplary embodiment of the invention described herein should also be read as applicable to other aspects or exemplary embodiments of the invention, where appropriate. In other words, a person skilled in the art reading this specification should consider any features for each exemplary embodiment of the invention to be interchangeable and combinable between different exemplary embodiments.

[0092] It should be understood that the use in the specification of words such as "preferable," "preferably," "preferred," or "more preferred" indicates that the feature so described may be desirable, but may nevertheless not be necessary, and embodiments lacking such features may be contemplated as being within the scope of the invention as defined in the appended claims. In the context of a claim, when words such as "a," "an," or "at least one" are used to preface a feature, no intention is intended to limit the claim to only such one feature, unless the claim specifically recites to the contrary.

[0093] Detailed Description of the Invention The invention will now be further described with reference to the following figures: [Brief description of the drawings]

[0094] [Figure 1] Figure 1: Improvement in skin health of subjects after 56 days of daily treatment with a probiotic composition. The percentage of subjects that showed improvement in skin health is shown. [Diagram 2]Figure 2: Skin health outcomes in subjects with psoriasis (overall skin health, skin sensitivity, skin itchiness, skin flaking and skin redness). Subjects received the probiotic composition daily for 56 days. Percentage of subjects with improvement and no change in skin health outcomes are shown. [Diagram 3] Figure 3: Skin health outcomes over time in psoriasis subjects (skin sensitivity, skin itchiness, skin flaking, and skin redness). Shows the percentage of subjects who experienced no change, slight improvement, much improvement, or very improvement in their skin health outcomes over 56 days of treatment with daily probiotic compositions. [Figure 4] Figure 4: Images showing the skin of a psoriasis subject at various times (A, B, C) throughout the study. [Diagram 5] Figure 5: Energy, sleep and mood benefits in psoriasis subjects who reported improved skin health. Percentage of subjects who showed improvement or no change in energy, sleep and mood are shown. [Figure 6] Figure 6: Improved skin health in subjects with eczema after 56 days of treatment with daily probiotic composition. The percentage of subjects showing improved skin health is shown. [Figure 7] Figure 7: Effect of Lc. cremoris W224, L. reuteri W192, L. brevis W63 and B. animalis W53 strains on IL-17 produced by anti-CD3 / anti-CD28 stimulated PBMCs after 72 h of co-culture. Unstimulated PBMCs and stimulated PBMCs without the addition of bacterial strains were used as controls. Values ​​for stimulated controls were set to 100% and are indicated by the dotted line. Dots represent values ​​for individual donors. Data represent the mean ± standard error of the mean. [Figure 8]Figure 8: Effect of Lc. cremoris W224, L. reuteri W192, L. brevis W63 and B. animalis W53 on IL-23 produced by activated DCs after 24 h co-culture. Unstimulated DCs and DCs stimulated with Th17 cocktail were used as controls. Dexamethasone was used as a positive control for Th17 inhibition. Values ​​for stimulated control were set as 100% and are indicated by dotted lines. Dots represent values ​​for individual donors. Data represent the mean ± standard error of the mean. [Figure 9] Figure 9: Effect of L. brevis W63 and B. animalis W53 on cytokine-induced barrier dysfunction after 24 h of incubation with TNF-α and IL-1β. The value of the control without added stressor was set as 100%. The dotted line indicates 80% protection of transepithelial electrical resistance (TEER) and the inverted triangles indicate strains with the ability to protect against cytokine-induced barrier dysfunction. Data represent the mean ± standard deviation.

[0095] As mentioned above, the present invention is based on the inventors' research showing that certain probiotic bacterial species and strains can reduce IL-17 and IL-23 levels and / or increase IL-10 levels and / or improve gut barrier function.Because subjects with dry and sensitive skin conditions such as psoriasis have been found to have elevated levels of IL-17 and IL-23, altered microbiomes and leaky gut, the inventors hypothesized that probiotic bacterial species could be used to treat and prevent dry and sensitive skin conditions.Human consumer studies conducted by the inventors showed that subjects treated with the probiotic bacterial composition according to the present invention showed improved skin health. EXAMPLES

[0096] Example 1 - Human Consumer Study Human consumer studies were conducted to establish the benefits of using the compositions of the present invention in subjects with dry and sensitive skin conditions such as psoriasis, atopic dermatitis, contact dermatitis, eczema, acne, rosacea and ichthyosis.

[0097] The study involved 267 subjects. Subjects could be male or female and were selected based on a medical history of having dry or sensitive skin conditions (psoriasis, eczema, rosacea, acne, etc.). Subjects were excluded if they were taking antibiotics, were pregnant, nursing or planning to become pregnant during the study period, or had an allergy or intolerance to any of the composition's ingredients.

[0098] Subjects were provided with a two month supply of the compositions of the present invention. Formulation details of the compositions used in the study are shown in Table 1 below:

[0099] [Table 1]

[0100] Before the study, subjects were asked to fill out some questions about their lifestyle and skin condition and to take photos of their skin. The study began the next day. One sachet (containing 3g of powder) was added to a small amount of warm water, stirred and then consumed. 3g (1 sachet) of the composition was taken daily on an empty stomach. During the study, subjects were asked to comment on their skin health and upload photos of their skin every 7 days to evaluate the effect of the composition on their skin health.

[0101] Subjects were asked to comment on their general skin health and the following specific skin health outcomes every 7 days during the study: itchiness; irritability; redness; smoothness; softness; blemishes; dryness; flakiness and firmness.

[0102] After 56 days of the study, 65% of subjects reported improved skin health (Figure 1). Specifically, 75% reported less itching, 74% reported less sensitivity, 73% reported less redness, 62% reported less dryness, and 64% reported fewer flaky patches. This demonstrates the effectiveness of the composition in treating dry and sensitive skin conditions, such as psoriasis, atopic dermatitis, contact dermatitis, eczema, ichthyosis, acne, rosacea, or Netherton syndrome. The 56-day data also showed that a significant proportion of subjects reported smoother skin (66%), softer skin (63%), and firmer skin (48%) along with fewer blemishes (59%), indicating that the composition may be effective in promoting cosmetic skin improvement.

[0103] Of the study participants, 177 had psoriasis. Specific skin health outcomes for psoriasis patients included skin sensitivity, itchy skin, flaky skin, and red skin. After 56 days of study, 91 psoriasis subjects reported outcomes. 72% of psoriasis subjects reported improvement in general skin health. Regarding psoriasis-specific outcomes, 73% of psoriasis subjects reported improvement in skin sensitivity, 76% of psoriasis subjects reported improvement in itchy skin, 65% of psoriasis subjects reported improvement in flaky skin, and 75% of psoriasis subjects reported improvement in red skin (Figure 2). In addition to the psoriasis-specific outcomes (sensitivity, itchiness, flaky skin, and redness), 69% of psoriasis subjects reported smoother skin, 64% reported softer skin, 62% reported fewer blemishes, and 49% reported firmer skin.

[0104] Skin health outcomes (itchiness, irritation, flakiness, and redness) in subjects with psoriasis were analyzed with subjects indicating they experienced no improvement, slight improvement, much improvement, or very improvement at 7, 14, 21, 28, and 56 days after beginning the study (Figure 3). Interestingly, for all skin health outcomes (itchiness, irritation, flakiness, and redness), the number of subjects reporting much improvement and very improvement increased over time, such that by day 56 after the study, 20-50% of subjects with psoriasis had much improvement and very improvement in their skin health outcomes. Improvement in skin condition was seen within 7 days, and improvement continued for the duration of the study.

[0105] Subjects were also asked to submit photos of their skin. Figure 4 shows the photos submitted by subjects with psoriasis (A, B, C). As shown in Figure 4, subjects showed clear improvement in their psoriatic skin condition, especially with continued use, with the most improvement seen by day 56. Subjects also provided written feedback. Subject B commented, "My skin looks better, less red and not as painful," and on day 42, "It's working great and getting better every week." Subject C commented, "The big patch on my elbow is gone... Also, the big hard patch behind my knee and up my thigh is much flatter."

[0106] Psoriasis has a significant psychological and social impact, can be isolating and can cause anxiety and depression. As part of the study, subjects were asked to comment on various lifestyle outcomes, particularly activity levels, sleep and mood. Among subjects with psoriasis who reported positive changes in skin health (itchiness, irritation, redness and flaking) at day 56, the majority experienced benefits in activity levels, sleep and mood (Figure 5). For example, of the 73% of subjects who reported reduced skin irritation at day 56, 64% felt more energetic, 65% slept better and 67% were in a better mood. Subjects who reported reduced itching, redness and flaking also experienced similar improvements in well-being.

[0107] These data demonstrate that subjects suffering from psoriasis showed significant improvements in both skin health and lifestyle outcomes (activity level, sleep and mood) following oral administration of a probiotic composition including Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis (Lactococcus cremoris). These data demonstrate that the compositions of the present invention are particularly effective in treating dry and sensitive skin conditions such as psoriasis.

[0108] Thirty-five of the study subjects suffered from eczema. At day 56 after the start of the study, 64% of the eczema subjects reported improved skin health (Figure 6). Specifically, 71% reported less itching, 71% reported less sensitivity, 64% reported less redness, 57% reported less dryness, and 64% reported less flaky spots. Additionally, 64% of the eczema subjects reported smoother skin, 64% reported softer skin, 64% reported less blemishes, and 57% reported firmer skin. This data indicates that the compositions of the present invention are also effective in treating eczema, another dry and sensitive skin condition.

[0109] Example 2 - In vitro testing The inventors performed in vitro testing of various probiotic bacterial species to determine their suitability for use in the treatment of dry or sensitive skin conditions. In particular, the inventors investigated the effects of these bacterial species on IL-17, IL-23 and IL-10 levels, as well as on intestinal barrier function (TEER measurements in intestinal epithelial cells) and in vitro models of inflammation (cytokine release by peripheral blood mononuclear cells).

[0110] Surprisingly, the inventors have found that certain bacterial species, such as Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis, are particularly effective in reducing IL-17 and IL-23 levels and / or increasing IL-10 levels and / or improving intestinal barrier function, thereby demonstrating their suitability for the treatment of dry and / or sensitive skin conditions such as psoriasis.

[0111] Inhibition of IL-17 produced by activated PBMCs Since a key role of IL-17 in the pathogenesis of psoriasis has been suggested, reducing IL-17 is thought to be therapeutically beneficial, as IL-17 is the main source of IL-17 and Th17 lymphocytes. Therefore, we investigated the effect of probiotic bacterial species on IL-17 levels using peripheral blood mononuclear cells (PBMCs).

[0112] method PBMCs are mononuclear cells isolated from peripheral blood, including lymphocytes, monocytes, and macrophages. PBMCs were isolated from three different human donors and stimulated with anti-CD3 / anti-CD-28 monoclonal antibodies, which are activators of T lymphocytes, to stimulate an inflammatory state. PBMCs were then co-cultured with different probiotic strains. PBMCs cultured in medium alone and PBMCs cultured in medium and stimulants served as controls for each donor. Lyophilized probiotic strains were reconstituted in cell culture medium before being added to the PBMC cultures. Culture supernatants were harvested after 72 h and IL-17 levels were measured by Luminex multiplex cytokine assay.

[0113] result The results shown in Figure 7 confirm that anti-CD3 / anti-CD-28 stimulation increases the secretion of IL-17 by PBMCs in all three donors (right bars) compared to unstimulated controls (left bars). When bacteria were co-cultured with stimulated PBMCs, the probiotic strains reduced the secretion of IL-17. The most prominent effect was observed with L. cremoris (L. lactis) W224 and L. reuteri W192. Beneficial effects were also seen with L. brevis W63 and B. animalis W53.

[0114] Inhibition of IL-23 produced by activated DCs A central role for the IL-23 / IL-17 axis in the immunopathogenesis of psoriasis has been proposed. IL-23 produced by activated dendritic cells (DCs) stimulates IL-17 production by these cells, as it is central to the survival and proliferation of Th17 lymphocytes. This increase in cytokines such as IL-17 results in an inflammatory cascade that leads to psoriatic disease. Thus, reducing IL-23 is thought to be of therapeutic value in reducing inflammation for psoriatic patients. Therefore, we investigated the effect of probiotic bacterial strains on in vitro IL-23 production by DCs.

[0115] method PBMCs were isolated from three different human donors and then cloned into CD14 + Mononuclear cells were purified and differentiated into Th17 DCs over 7 days. DCs were then co-cultured with different probiotic strains. Untreated and dexamethasone-treated DCs served as controls for each donor. Dexamethasone was used as a positive control for Th17 inhibition. Lyophilized probiotic strains were reconstituted in cell culture medium before being added to DC cultures. After 6 h of incubation with probiotic strains, the TH17 cocktail was added to DCs. After 24 h of co-culture with probiotic strains, supernatants were collected. IL-23 was measured in duplicate by Luminex.

[0116] result The results shown in Figure 8 confirm that the TH17 cocktail induces IL-23 secretion in all three DC donors compared to the unstimulated control. Dexamethasone, a positive control for Th17 inhibition, convincingly inhibits IL-23 secretion in all three donors (Figure 8). After co-culture of bacterial strains with stimulated DCs, L. reuteri W192, L. brevis W63, B. animalis W53 and Lc. cremoris (L. lactis) W224 reduced IL-23 secretion. L. reuteri W192 and L. brevis W63 reduced IL-23 secretion to below 55% in all three donors compared to stimulated DCs.

[0117] Inhibition of cytokine-induced barrier breakdown (TEER) The intestinal barrier plays a key role in the communication between the intestine and the rest of the human body. Maintenance of the integrity of the intestinal epithelium, and thus the barrier function, is important for essential physiological processes, and increased permeability can lead to elevated levels of bacterial antigens in the circulating blood, which leads to systemic low-grade inflammation, a hallmark of various diseases such as psoriasis. Therefore, we sought to measure the effect of probiotic bacterial species on the intestinal epithelial barrier. Measurement of transepithelial electrical resistance (TEER) is a widely accepted quantitative technique to measure the integrity of tight junction dynamics in cell culture models of epithelial monolayers. A decrease in TEER indicates impaired intestinal barrier function.

[0118] method Monolayers of Caco-2 cells were first exposed to probiotic bacterial strains for 2 hours and then exposed to inflammatory stressors (TNF-α and IL-1β) in the presence of the same probiotic bacterial strains. After 24 hours, the TEER of the monolayers was measured. The results were compared to the TEER of Caco-2 monolayers exposed to the stressors alone and to Caco-2 monolayers not exposed to the stressors. This last control was set to 100% (see Figure 9). Each condition was measured in duplicate.

[0119] result As shown in Figure 9, B. animalis W53 and L. brevis W63 exhibited a significant effect in protecting epithelial cells from cytokine-induced barrier dysfunction, and were able to maintain TEER above 90% after inflammatory stress, indicating a beneficial effect on intestinal barrier function.

[0120] Example 3 - Human Clinical Study In order to further develop the compositions of the present invention, the inventors have designed a human clinical trial to be carried out in a dermatology clinic in the North West of England.

[0121] Subjects were men or women aged 18-70 years, selected based on a history of stable plaque psoriasis without flare-ups in the 4 weeks prior to the start of the study, with a PASI score of >3. Subjects were excluded if they were taking antibiotics, had GI diseases or were on a special diet, had received phototherapy or systemic therapy (except methotrexate) within the past 3 months, had taken probiotics and / or prebiotics in the 2 weeks prior to the study, were pregnant, breastfeeding, or planning to become pregnant during the study period, or had an allergy or intolerance to any of the components of the composition.

[0122] The test product will be blinded to the subjects and the clinical team. Each subject will be asked to take the test product daily for a total of six months. The study has two arms, each of which will recruit 50 volunteers with mild to moderate psoriasis (25 placebo and 25 inventive composition): Arm 1: psoriasis patients currently prescribed methotrexate, and Arm 2: treatment-naive psoriasis patients not prescribed medication. Each subject will visit the center for evaluation at weeks 1, 6, 12 and 26. At each visit, skin, blood and stool samples will be collected for microbiome analysis, biomarkers (IL1β, IL17, IL23 and TNF-α) and disease severity assessment. Subjects will complete weekly questionnaires.

[0123] Outcomes will be assessed at the end of the study.

[0124] It will be understood that many modifications to the above method can be made without departing from the scope of the present invention as defined in the appended claims.For example, although a powder form of the composition is illustrated, it will be understood that the composition can be in any suitable form, such as liquid, solution, suspension, syrup, tablet, granule or capsule.Furthermore, although the examples focus on compositions containing Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis (Lactococcus cremoris), other suitable probiotic bacteria can also be included in the compositions of the present invention.

Claims

1. 1. A composition for use in the treatment and / or prevention of a dry and / or sensitive skin condition in a subject, the composition comprising at least two bacterial species that reduce levels of interleukin-17 and / or interleukin-23 in said subject, increase levels of interleukin-10 in said subject, and / or improve intestinal barrier function in said subject.

2. A composition for use according to claim 1, wherein the bacterial species is selected from the following: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri, Lactococcus lactis / Lactococcus cremoris, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium infantis, Lactobacillus plantarum, Lactobacillus pentosus, Lactobacillus paracasei, Lactobacillus paracasei), Lactobacillus acidophilus and Bifidobacterium breve.

3. A composition for use as described in claim 1, wherein the composition comprises at least two bacterial species selected from the group consisting of: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

4. A composition for use according to any one of claims 1 to 3, wherein the composition comprises at least three bacterial species selected from the group consisting of: Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

5. The composition for use according to any one of claims 1 to 4, wherein the composition comprises B. animalis, L. brevis, L. reuteri and L. lactis / Lc. cremoris.

6. A composition for use according to any one of claims 1 to 5, wherein the dry and / or sensitive skin condition comprises psoriasis, atopic dermatitis, contact dermatitis, eczema or ichthyosis.

7. A composition for use according to any one of claims 1 to 6, wherein the dry and / or sensitive skin condition comprises psoriasis.

8. The bacterial species is 10 6 From 10 12 cfu / g, preferably at a concentration of approximately 10 9 The composition for use according to any one of claims 1 to 7, which is present in the composition at a concentration of cfu / g.

9. The composition for use according to any one of claims 1 to 8, wherein the composition is formulated for oral administration.

10. A composition for use according to any one of claims 1 to 9, wherein the composition comprises a powder.

11. A composition comprising at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23, increases levels of interleukin-10, and / or improves intestinal barrier function.

12. The composition of claim 11, comprising at least two bacterial species selected from the group consisting of Bifidobacterium animalis, Lactobacillus brevis, Lactobacillus reuteri and Lactococcus lactis / Lactococcus cremoris.

13. The composition of claim 11 or 12, wherein the composition comprises B. animalis, L. brevis, L. reuteri and L. lactis / Lc. cremoris.

14. The bacterial species is 10 6 From 10 12 cfu / g, preferably at a concentration of approximately 10 9 The composition according to any one of claims 11 to 13, which is present in the composition at a concentration of cfu / g.

15. The composition of any one of claims 11 to 14, wherein the composition is formulated for oral administration.

16. The composition of any one of claims 11 to 15, wherein the composition comprises a powder.

17. A combination for use in the treatment and / or prevention of a dry and / or sensitive skin condition in a subject, comprising at least two bacterial species that reduce levels of interleukin-17 and / or interleukin-23 in the subject, increase levels of interleukin-10 in the subject, and / or improve intestinal barrier function in the subject.

18. A composition for use in the treatment and / or prevention of a dry and / or sensitive skin condition in a subject, comprising one of at least two bacterial species that reduce levels of interleukin-17 and / or interleukin-23 in said subject, increase levels of interleukin-10 in said subject, and / or improve intestinal barrier function in said subject; The composition, wherein the composition is administered to the subject in combination with an administration of at least one other of the at least two bacterial species.

19. A combination comprising at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23, increases levels of interleukin-10, and / or improves intestinal barrier function.

20. A composition comprising one of at least two bacterial species that reduces levels of interleukin-17 and / or interleukin-23, increases levels of interleukin-10, and / or improves intestinal barrier function, provided in combination with a composition comprising at least one other of the at least two bacterial species.

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