WO2017085655A1

WO2017085655A1 - Compositions with a synergistic action between a mucoadherent gelling complex against the passage of antigens, and immunomodulatory anti-il17 bacteria for use in the treatment of un¬ related autoimmune and neurodegenerative diseases.

Info

Publication number: WO2017085655A1
Application number: PCT/IB2016/056918
Authority: WO
Inventors: Giovanni Mogna
Original assignee: Probiotical SpA
Current assignee: Probiotical SpA
Priority date: 2015-11-18
Filing date: 2016-11-17
Publication date: 2017-05-26
Anticipated expiration: 2018-05-18
Also published as: ITUB20155700A1; HK1255849A1; EP3377083A1

Abstract

The present invention relates to compositions with a synergistic action between a mucoadherent gelling complex against the passage of antigens, and immunomodulatory anti-IL17 bacteria for use in the treatment of IL-17-related autoimmune and neurodegenerative diseases.

Description

DESCRIPTION of the invention entitled:

Compositions with a synergistic action between a mucoadherent gelling complex against the passage of antigens, and immunomodulatory anti-IL17 bacteria for use in the treatment of Unrelated autoimmune and neurodegenerative diseases.

The present invention relates to compositions with a synergistic action between a mucoadherent gelling complex against the passage of antigens, and immunomodulatory anti-IL17 bacteria for use in the treatment of IL17-related autoimmune and neurodegenerative diseases.

Alteration of the intestinal permeability, also referred to as Leaky Gut Syndrome, is known to be at the basis of several diseases among which Candida infection, Crohn's disease, atopic eczema, food intolerances and allergies, asthma, arthritis and all the autoimmune and neurodegenerative diseases in general.

The immune system exerts its activity of control at lymphatic ganglia of intestine and walls thereof (in particular in the small intestine by the Peyer's plaques) where acts avoiding the passage of body's dangerous or harmful substances.

Under healthy conditions, the digestive system is well functioning and, thus, only few, carefully selected components can cross the intestinal mucosa and enter the bloodstream. However, under non-optimal conditions, inflammation of the intestinal mucosa, in particular of the colon and rectum, can occur, with a consequent reduction of its capability of selective permeability. Furthermore, a dysbiotic intestine, namely with an impaired and poor bacterial flora, allows several toxics to accumulate therein, continuously overloading the immune system (IS), which can lose over time its efficiency and cause several dysfunctions and diseases.

Some studies demonstrate that a pathological intestinal permeability can be seriously harmful for the health. For example, an increased intestinal permeability leads to a failure of the intestinal defence abilities allowing even to large peptides, toxins, bacteria, pathogens, yeasts, fungi and parasites, in contrast to normal conditions, to overcome the protective barrier, consisting of the intestinal mucosa, and enter the bloodstream.

Pathogenic bacteria attack and penetrate more easily the intestinal mucosa when the intestinal mucosa is inflamed and/or the mucus is poor in the intestinal wall. Therefore, it is imperative to be able to preserve the intestinal mucosa in order to avoid, reduce or, at least, counteract the harmful action of pathogenic bacteria.

The increase in intestinal permeability leads to a failure of the intestinal defence abilities; large peptides, bacteria, fungi and parasites, which under normal conditions could not cross the intestinal mucosa, are now able to pass it, thus triggering the reaction of the Immune System (IS). A high intestinal permeability, referred to as Leaky Gut Syndrome, has been related for example to some forms of arthritis, besides food allergies and intolerances, and is also found in autoimmune diseases. The continuous exposure to substances, with a too permeable intestine being unable to preventing their absorption, allows to also overcome the detoxifying function of the liver thus causing several symptoms.

Therefore, thus far, it is obvious that under healthy conditions, only few food antigens are able to overcome the intestinal wall and are immediately neutralized. However, if the amount of these antigens is high, non-specific immune cells, mast cells and immature IgMs, become saturated thus allowing other antigens to cross the intestinal mucosa triggering a high antibody response. When these antigens are also allergens, they would reach, via the bloodstream, the mucosae of the respiratory tract and skin, which are areas rich in specific antibodies, IgEs. Such IgEs, binding to mast cells, which recognized the antigen, would trigger the release of chemical mediators.

It is thus clear that the intestinal permeability is the cause leading to an overproduction of cytokines such as, for example, cytokines of IL-17 family, which comprise proinflammatory cytokines (interleukins) such as IL-17A, IL-17B, IL-17C, IL-17D and IL-17F produced by Th17 cells.

Interleukin 17 (IL-17 or IL-17A) is produced by T helper 17 lymphocytes (human proinflammatory cells - Th17) and induced by IL-23. Th17 cells are involved, by way of a non-limiting example, in psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, which is an inflammatory disease characterized by an usually reversible obstruction of lower airways and, therefore, only involves the respiratory tract, epilepsy, cerebral ischemia, lupus erythematosus, uveitis and chronic pelvic pain syndrome (CPPS).

From a functional point of view, IL-17 belongs to the molecules of both innate and adaptive immunity. As stated above, the maintenance of an optimal functionality condition of both the innate (non-specific or natural) and adaptive (specific) immune system is fundamental for the body's defence against invading pathogens. An intact and well-functioning intestinal mucosa provides a defence barrier against potentially harmful antigens to the host, controlling the tolerance effects towards them.

Psoriasis is a chronic inflammatory disease, which affects up to 3% of the world's population. The immune system plays a main role in psoriasis development since the immune system (IS) produces several proteins called cytokines, which act as "messengers", coordinating the signalling among the immune cells in response to an infection. One of these cytokines, interleukin-17A (IL-17A), is believed to play a key role in the development of psoriasis. The occurrence of higher skin levels of IL-17A can trigger an immune response even in the absence of an infectious stimulus, thus causing inflammatory symptoms such as itching and redness. Furthermore, IL-17A stimulates the skin production of new cells at a higher than normal rate, thereby leading to symptoms typical of psoriasis, such as skin thickening and plaques (scaly skin), due to the build-up of cells over the skin surface.

Interleukin-17A (IL-17A) is one of the many "messenger" proteins called cytokines, which are responsible, in our body, for the coordination of signals among immune cells. Usually, cytokines act by stimulating the infection-fighting cells to trigger an immune response against a foreign agent. IL-17A proved to have a key role in some immune-mediated diseases, such as moderated to severe plaque psoriasis, and is considered a main target for measuring the efficacy of developing therapies.

Psoriasis, which is characterized by epidermal hyperplasia is, thus, a disease different from atopic dermatitis, since the latter is a chronic inflammatory, but non-autoimmune disease of the skin, which can be caused by a deficient barrier function of the skin and mainly affects pediatric patients (about 0-14 years). The most common symptom of atopic dermatitis is the eczema, namely redness of the skin, which results dry, irritated and sometime with small liquid-filled blisters, which can become swollen.

Psoriasis (autoimmune disease) is a systemic inflammatory disease due to a dysregulation of the immune system. IL-17A is found at higher concentrations in the psoriatic skin, with up to six-fold greater amount than those found in a non-psoriatic cutis. Higher skin amounts of IL-17A were also related to a more severe psoriasis.

For example in the case of systemic lupus erythematosus (SLE) Th17 cells and cytokines IL-17 (IL-17A) were reported to play a main role in SLE pathogenesis. Similarly, with reference also to rheumatoid arthritis, multiple sclerosis and noninfectious uveitis, Th17 cells and cytokines IL-17 (IL-17A) were found to play a main role in the corresponding diseases.

Recent studies found that IL-17A triggers a vicious circle in psoriasis, as it sends signals to the skin and immune system cells, provoking the typical symptoms of the disease. For this reason, IL-17A was identified as the main target of the treatment and the pharmacological research focused in developing drugs, which directly or indirectly inhibit IL-17A.

However, the concept of "direct or indirect inhibition" of IL-17A does not lead to significant results as demonstrated by studies (for example the article entitled "Targeting of interleukin-17 in the treatment of psoriasis" -Clinical Cosmetic and Investigational Dermatology 2014:7 251-259) carried out with therapies based on biological drugs such as Brodalumab, which blocks the subunits of IL-17RA receptors; monoclonal antibody Secukinumab for the IL-17A ligand which selectively neutralizes IL-17A; Ixekizumab which is a humanized monoclonal anti-IL-17 antibody. As regards the above biological drugs, which are highly expensive, additional long-term studies are required in order to carefully determining the efficacy, side effects and safety thereof. Indeed, as set forth in the above-cited article, the administration of biological drugs results in the almost complete suppression, which cannot be modulated, of cytokines IL- 17, which exposes the treated subject to even severe infections, and tumors, since the main function of IL- 17 is to protect against infectious diseases.

Therefore there is a need for having a novel therapy or combined treatment system which is natural, effective, inexpensive, safe for the treated subjects and devoid of side effects for the treatment of an autoimmune disorder or disease, neurodegenerative disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 (IL-17, IL-17A). The Applicant, following to a long and intense research and development activity, succeeded to suitably meet the above-cited needs by developing a composition being natural, effective, safe for the treated subjects and devoid of side effects.

It is an object of the present invention the compositions having the technical characteristics as set forth in the appended claims.

The technical solution underlying the present invention advantageously solves the technical problem at the basis of the present invention by acting, in a combined way, with a double action: the first one is directed and aimed to reducing/decreasing the intestinal permeability, thereby reducing the antigens which overcome the barrier and, thus, intrinsically reducing the body's overproduction of cytokines such as IL-17, while the second action is directed as interventional activity directly on the immune system so that to decrease/modulate the immune response with a further reduction of the level of cytokines such as IL-17. The technical solution underlying the present invention entails that a reduced intestinal permeability leads to a decrease of antigens, which overcome the intestinal barrier. A reduced amount of antigens, which cross the intestinal barrier, results in a lower body's overproduction of cytokines such as IL-17 (IL-17A). Then, the residual amount of IL-17 (IL-17A), if any, is further reduced by the modulation of the immune response, instead of a direct or indirect inhibition of IL-17 (IL-17A).

With reference to the aspect concerning the modulation of the immune response, the Applicant, contrary to the teachings of the known technique, which lead to a "direct or indirect inhibition" of IL-17A, applied a novel therapeutic concept based on the principle of modulating the IL-17 reduction (rather than inhibiting the IL-17 production) to such an extent that IL-17 keeps and maintains its protective function against infections.

Therefore, the Applicant developed compositions having a synergistic action because of the presence of both a mucoadherent gelling complex, which plays a targeted action against the passage of antigens, and selected immunomodulatory anti-IL17 (IL-17A) bacteria, said compositions being for use in the treatment of IL17-related autoimmune and neurodegenerative diseases.

Advantageously, the compositions of the present invention are for oral use and useful in the preventive or curative treatment of an autoimmune disorder or disease or neurodegenerative disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing cytokines such as interleukins-17 (IL-17, IL-17A), wherein said treatment can comprise reducing or inhibiting the production of interleukins-17 (IL-17, IL-17A).

Preferred embodiments of the present invention are hereinafter reported in order to better describe the object of the present invention, without wishing to limit in any way the scope thereof.

Table 1 reports a list of strains of Lactobacilli being used in the present in vitro study.

Table 2 reports a list of strains of Bifidobacteria being used in the present in vitro study.

Figure 1 reports the interleukin-17 modulation by strains belonging to the genus Lactobacillus. Figure 2 reports the interleukin-17 modulation by strains belonging to the genus Bifidobacterium.

Figure 3 reports the strains with inhibitory ability belonging to the genus Lactobacillus.

Figure 4 reports the strains with inhibitory ability belonging to the genus Bifidobacterium.

Within the context of the present invention by autoimmune and neurodegenerative diseases and systemic inflammatory disease are meant those related to an overproduction of IL-17 such as, by way of a non- limiting example, psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS).

Furthermore, within the context of the present invention by "composition of the present invention" is meant to encompass pharmaceutical compositions, compositions for medical devices, food compositions and compositions for supplement products.

The composition of the present invention comprises a mixture which comprises or, alternatively, consists of: (i) a first selection of bacterial strains, said bacterial strains producing in situ in the gastrointestinal tract bacterial gums such as exopolysaccharides (briefly, EPS), once administered; (ii) vegetable gums and (iii) a second selection of bacterial strains.

Said bacterial gums being produced by selected bacterial strains (i) in situ in the gastrointestinal tract. Said bacterial gums being produced in the presence of said vegetable gums (ii) after the administration of said mixture present in said composition. Said bacterial gums being produced in situ directly in the gastrointestinal tract by selected bacterial strains (i), along with vegetable gums (ii), are able to preserve and protect the intestinal mucosa so that to avoid, reduce or at least counteract the harmful action of pathogenic bacteria to the mucosa itself.

Said mixture comprises at least a strain of bacteria (i) (which produces in situ directly in the gastrointestinal tract said bacterial gums such as exopolysaccharides (briefly, EPS)), a vegetable gum (ii) and a second selection of bacterial strains (iii).

Said at least one strain of bacteria (i) producing EPS is selected from the group comprising the bacterial strains belonging to the genus Streptococcus, Lactobacillus and Bifidobacteria. Said at least a strain of bacteria (i) is preferably selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus pentosus, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus reuteri, Bifidobacterium breve, Bifidobacterium bifidum, Bidifobacterium lactis, Lactobacillus fermentum and Lactobacillus delbrueeckii.

Said at least one strain of bacteria (i) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus. Said bacterial strains (i) should produce, once administered, EPS in situ in the gastrointestinal tract. Advantageously, said bacterial strains (i) producing EPS in situ in the gastrointestinal tract belong to the species Streptococcus thermophilus.

Advantageously, said mixture comprises at least one strain of bacteria (i) (which produces in situ directly in the gastrointestinal tract said bacterial gums such as exopolysaccharides (briefly EPS)) belonging to the species Streptococcus thermophilus, a vegetable gum (ii) and a second selection of bacterial strains (iii). Said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of the bacterial strains belonging to the species Lactobacillus salivarius.

Said mixture can comprise at least one, or two or three or four bacterial strains (i) producing EPS, preferably belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus, combined with a vegetable gum (ii) and a second selection of bacterial strains (iii). Said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius.

Advantageously, said at least one, or two or three or four bacterial strains (i) producing EPS in situ in the gastrointestinal tract belong to the species Streptococcus thermophilus. Said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius.

The present invention further encompasses embodiments comprising mixtures of two or three or four bacterial strains selected from bacterial strains belonging to the species Streptococcus thermophilus and/or Lactobacillus plantarum and/or Lactobacillus rhamnosus, combined with a vegetable gum (ii) and a second selection of bacterial strains (iii). Said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius.

A gum is a dehydrated or freeze-dried or dry powdery or flake-like material which, once contacted with water, produces a gel of gum in water (aqueous gel) or a gum gelatin. Alternatively, a previously prepared gel or gelatin can be suitably used. Gums used within the context of the present invention are all gums for oral use being approved and used for food supplement products and medical devices.

Said vegetable gum (ii) present in said mixture, contained in the compositions of the present invention is selected from the group comprising or, alternatively, consisting of Aloe, Aloe vera (Aloe vera -Aloe barbadensis Miller, is a plant of the Aloeacee family), Aloe arborescens, alginates, xyloglucans (or xylogel), carrageenans, pectins, agar-agar and tara gum.

Advantageously, the vegetable gum (ii) contained in said mixture is selected from the group comprising or, alternatively, consisting of Aloe, Aloe vera, Aloe arborescens and tara gum.

Said mixture can comprise at least one, or two or three or four bacterial strains (i) producing EPS, preferably belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus, combined with a vegetable gum (ii) selected from Aloe, Aloe vera, Aloe arborescens and tara gum, and a second selection of bacterial strains (iii). Said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of the bacterial strains belonging to the species Lactobacillus salivarius.

Advantageously, said at least one, or two or three or four bacterial strains (i) producing EPS in situ in the gastrointestinal tract belong to the species Streptococcus thermophilus.

Advantageously, said vegetable gum (ii) is a commercially available tara gum.

The bacterial gum produced in situ in the gastrointestinal tract by bacterial strains (i), once administered, and the vegetable gum (ii) mechanically protect the inflamed intestinal mucosae. The vegetable gum (ii), such as tara gum, forms a protective mucoadherent film of protein origin which protect the intestinal mucosa. However, a vegetable gum (ii), such as for example tara gum, from its ingestion until it reaches the intestine, is subjected to a slow but continuous degradation during its transit from the stomach to the intestine. The vegetable gum (ii) degrades and loses its efficacy of restoring the physiological functions of the intestine walls.

This degradation is due to multiple factors such as for example pH, enzymes, attacks to the endogenous bacterial flora, the effect of the gastroduodenal barrier and a dilution effect. Basically, there is an increasing loss of efficacy when the vegetable gum (ii), such as for example tara gum, passes the gastrointestinal tract even after an acidic attack, by bile salts, pancreatic juices, enzymes. When the vegetable gum (ii), such as for example tara gum, reaches the colon is partially degraded and, thus, is less effective in protecting the intestine walls from pathogenic bacteria, which are able to penetrate them through their flagella.

The Applicant found that the bacterial gum, produced in situ by the strains (i) of the present invention selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus, on the one hand, and a vegetable gum (ii), on the other hand, they each have their own effect being complementary to each other.

The first effect is a gelling effect exerted by the vegetable gum (ii), which is maximum in the stomach (maximum protection) and minimum in the colon, because of the degradation and consequent loss of efficacy in protecting the inflamed intestinal mucosae.

The second effect is a protective effect exerted by the bacterial gum, in particular by exopolysaccharides (EPS) produced in situ by the strains of the present invention selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus. This second effect is minimum in the stomach and maximum in the colon where the bacteria of the present invention, which arrive alive and viable and at a high concentration, produce EPS in situ directly in the gastrointestinal tract. These two complementary effects, combined together, assure a full protection throughout the stomach (due to the vegetable gum (ii)) and gastrointestinal tract (due to the bacterial gum) against bacterial infections.

The composition of the present invention as a result of said two complementary effects exerted by the vegetable gum (ii) and the bacterial gum, respectively, allows to reduce/decrease the intestinal permeability, in order to thereby lessening the antigens which overcome the barrier and, thus, intrinsically reducing the body's overproduction of cytokines such as IL-17 (IL-17A) (first action).

The compositions of the present invention are able to restore the deficient barrier effect, resulting from a poor protection of the mucosa of the gastrointestinal tract.

The compositions of the present invention are able to prevent and cure infections, inflammations and disorders of the gastrointestinal system, pathogenic bacteria, candidiasis and intestinal permeability. The composition of the present invention is able to form a specific mucoadherent gelling complex, consisting of EPS, bacterial exopolysaccharides (produced by selected strains of bacteria (i) and listed below, in particular belonging to the species Streptococcus thermophilus, such as for example Streptococcus thermophilus ST10 -DSM 25246, Streptococcus thermophilus (Y04) DSM 16592 or mixtures thereof in a weight ratio comprised from 1 :2 to 2: 1 , preferably 1 : 1, and a vegetable gum (ii) such as tara gum, a plant polysaccharide. Said gelling complex is able to establish a mechanical barrier effect of protection throughout the gastrointestinal tract.

The composition of the present invention due to the presence of the gelling tara gum, is able to form a hydrogel within few minutes from ingestion because of its thixotropic characteristics and thereby create in the first gastrointestinal tract a mechanical barrier effect against pathogenic bacteria and metabolites with proinflammatory activity. Such a barrier effect is completed and extended throughout the gastrointestinal tract by the presence of exopolysaccharides (EPS), produced in situ by the bacterial strains belonging to the species Streptococcus thermophilus, listed below, such as for example Streptococcus thermophilus ST10, Streptococcus thermophilus YO04 or mixtures thereof, which thereby enhance the viscosity of the surrounding environment through a self-controlled and only mechanical mechanism. By the intake of said bacterium, a source of molecules with gelling activity is carried to the human intestine, thus exerting a fully complementary action to that of the vegetable gum (ii) such as tara gum. The above-cited mucoadherent gelling complex has an innovative property to be considered: the tara gum (similarly to all plant gums) is gradually degraded during its intestinal transit by the resident microbiota, thus progressively reducing its gelling power of mechanical hindrance. The gradual lessening of the vegetable gum action is effectively counterbalanced by the increasing release of exopolysaccharides (EPS) in the intestinal lumen by for example the bacterial strain ST10 and/or YO04, which mainly exhibits its peculiarity in the ileum and colon. The synergistic combination among tara gum and exopolysaccharides (EPS) thus ensures the presence of gelling molecules throughout the gastrointestinal tract, maximizing and optimizing the mechanical barrier action of the product. The presence, production and maintenance of the hydrophilic gel in the lumen of the organ can, therefore, be considered for the first time really complete, with a first area wherein the action of the vegetable gum is maximum, and a second area wherein the action of exopolysaccharides (EPS) is maximum.

Advantageously, the bacterial strains (i) comprised in said mixture contained in turn in the composition of the present invention are selected from the group comprising or, alternatively, consisting of:

- Streptococcus thermophilus DSM 16590 (Y02) deposited at the DSMZ institute in Germany on 20/07/2004,

- Streptococcus thermophilus DSM 16592 (Y04) deposited at the DSMZ institute in Germany on 20/07/2004,

- Streptococcus thermophilus DSM 17843 (Y08) deposited at the DSMZ institute in Germany on 21/12/2005,

- Streptococcus thermophilus DSM 25246 (ST10) deposited at the DSMZ institute in Germany on 19/09/2011 ,

- Streptococcus thermophilus DSM 25247 (ST11) deposited at the DSMZ institute in Germany on 19/09/2011 ,

- Streptococcus thermophilus DSM 25282 (ST12) deposited at the DSMZ institute in Germany on 20/10/2011.

Bacterial strains were deposited according to the Budapest Treaty and are publicly available.

In an embodiment the composition of the present invention comprises a mixture which comprises or, alternatively, consists of at least one, or two or three or four bacterial strains (i) selected from the group comprising or, alternatively, consisting of: Streptococcus thermophilus DSM 16590 (Y02), Streptococcus thermophilus DSM 16592 (Y04), Streptococcus thermophilus DSM 17843 (Y08) and Streptococcus thermophilus DSM 25246 (ST10), combined with a vegetable gum (ii) selected from Aloe, Aloe vera, Aloe arborescens and tara gum, and at least a strain of bacteria selected from a second selection of bacterial strains (iii). Advantageously, said vegetable gum (ii) is a tara gum, and said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius, such as those hereinafter referred to as (a), (b), (c), (d) and (e). In another embodiment the composition of the present invention comprises a mixture which comprises or, alternatively, consists of Streptococcus thermophilus DSM 25246 (ST10), combined with a vegetable gum (ii) selected from Aloe, Aloe vera, Aloe arborescens and tara gum, and at least a strain of bacteria selected from a second selection of bacterial strains (iii). Advantageously, said vegetable gum (ii) is a tara gum, and said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius, such as those hereinafter referred to as (a), (b), (c), (d) and (e), preferably that referred to as (a). In another embodiment the composition of the present invention comprises a mixture which comprises or, alternatively, consists of Streptococcus thermophilus DSM 25246 (ST10) and at least a strain selected from Streptococcus thermophilus DSM 16590 (Y02), Streptococcus thermophilus DSM 16592 (Y04), Streptococcus thermophilus DSM 17843 (Y08), combined with a vegetable gum (ii) selected from Aloe, Aloe vera, Aloe arborescens and tara gum, and at least a strain of bacteria selected from a second selection of bacterial strains (iii). Advantageously, said vegetable gum (ii) is a tara gum, and said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius, such as those hereinafter referred to as (a), (b), (c), (d) and (e), preferably that referred to as (a).

In another embodiment the composition of the present invention comprises or, alternatively consists of Streptococcus thermophilus DSM 25246 (ST10) and Streptococcus thermophilus DSM 16592 (Y04), combined with a vegetable gum (ii) selected from Aloe, Aloe vera, Aloe arborescens and tara gum, and at least a strain of bacteria selected from a second selection of bacterial strains (iii). Advantageously, said vegetable gum (ii) is a tara gum, and said second selection of bacterial strains (iii) is selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius, such as those hereinafter referred to as (a), (b), (c), (d) and (e), preferably that referred to as (a).

It is an object of the present invention a pharmaceutical composition, or a composition for medical devices, or a composition for a supplement product or a composition for a food product, comprising a mixture, which comprises or, alternatively, consists of:

(i) a first selection of bacterial strains, said bacterial strains producing in situ in the gastrointestinal tract bacterial gums such as exopolysaccharides (briefly, EPS), once administered; (ii) vegetable gums and (iii) a second selection of bacterial strains;

said composition being for use in the preventive or curative treatment of an autoimmune disorder or disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 -IL-17, said composition being for use in the preventive or curative treatment of an autoimmune or neurodegenerative disorder or disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 (IL-17, IL- 17A) wherein said autoimmune or neurodegenerative disease or systemic inflammatory disease is selected from the group comprising or, alternatively, consisting of psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS).

Said treatment preferably comprises the reduction or inhibition of the production of interleukins-17 (IL-17, IL-17A). Th17 cells are involved, by way of a non-limiting example, in psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis and chronic pelvic pain syndrome (CPPS).

Said second selection of bacterial strains (iii) relates to a selection of lactic bacteria for use in the preventive or curative treatment of an autoimmune disorder or disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins- 17 -IL-17, having the characteristics as set forth in the appended independent claim. Th17 cells are involved, by way of a non-limiting example, in psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS). Said strains of lactic bacteria (iii) belong to the species Lactobacillus salivarius.

Advantageously, said at least one strain of bacteria selected from said second selection of bacterial strains (iii) belongs to the species Lactobacillus salivarius and is selected from the group comprising or, alternatively, consisting of:

(a) Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical SpA,

(b) Lactobacillus salivarius DSM 32204 (LS02), deposited on 13/11/2015 at the DSMZ institute by Probiotical SpA,

(c) Lactobacillus salivarius DSM 22776 (LS03), deposited on 23/07/2009 at the DSMZ institute by Probiotical SpA,

(d) Lactobacillus salivarius DSM 26037 (LS06), deposited on 06/06/2012 at the DSMZ institute by Probiotical SpA,

(e) Lactobacillus salivarius DSM 29476 (LS07), deposited on 09/10/2014 at the DSMZ institute by Probiotical SpA.

Said at least a strain of bacteria selected from said second selection of bacterial strains (iii) can also be selected from the group comprising or, alternatively, consisting of:

(f) Lactobacillus plantarum LMG P-21021 (LP01), deposited on 16/10/2001 at the BCCM LMG Institute by Mofin S.r.l.

(g) Lactobacillus reuteri DSM 23880 (LRE04), deposited on 05/08/2010 at the DSMZ institute by Probiotical SpA,

(h) Lactobacillus reuteri DSM 25685 (LRE09), deposited on 16/02/2012 at the DSMZ institute by Probiotical SpA,

(i) Lactobacillus delbruekii DSM 22106 (LDD01), deposited on 10/12/2008 at the DSMZ institute by Probiotical SpA,

(I) Bifidobacterium breve DSM 29494 (BR05), deposited on 09/10/2014 at the DSMZ institute by Probiotical SpA. In a preferred embodiment, in the composition for use according to the present invention the bacterial strain (iii) is Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical SpA.

In a preferred embodiment, in the composition for use according to the present invention the bacterial strain (i) is Streptococcus thermophilus DSM 25246 (ST10), deposited at the DSMZ institute in Germany on 19/09/2011 , combined with a vegetable gum (ii), which is tara gum, and the bacterial strain (iii) is Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical SpA.

Every single bacterial strain (i) and/or (iii) is present in said mixture, contained in the composition of the present invention, at a concentration comprised from 1x10⁶ to 1x10¹¹ CFU/g, preferably from 1x10⁸ to 1x10¹⁰ CFU/g. Bacterial strains (i) and/or (iii) can be present in said mixture, contained in the composition of the present invention, in a solid or powdery or freeze-dried form.

Bacterial strains (i) and/or (iii) can be present in said mixture, contained in the composition of the present invention, as live or died, sonicated, tyndallized or lysed cells, or as enzymes or components extracted from bacterial cells.

In the case of bacterial strains (i) belonging to the species Streptococcus thermophilus, said bacteria are in a protected form (coated bacteria). In the case of bacterial strains (iii) belonging to the species Lactobacillus salivarius, said bacteria can preferably be in a protected form (coated bacteria). In both the cases, when bacteria (i) and (iii) are in a protected form, they can be coated with a lipid coating (single- coated or single-coating) or with two lipid coatings (bi-coated or double coating) of animal or plant origin (microencapsulated form). The lipid coating has a melting point comprised from 35 to 85°C, preferably from 45 to 75°C, even more preferably from 55 to 65°C.

The lipid coating can be a single coating or a double coating made with the same or different lipids. Coating is prepared by using the equipment, lipids and techniques known to the skilled in the field.

The mixture is contained in the composition of the present invention in a weight ratio of 1 :1 (50% of the total weight of the composition) or in an amount by weight comprised from 50% to 75%, relative to the total weight of the composition.

As regards the mixture contained in the composition of the present invention, said mixture contains the bacterial strains (i) in a weight ratio relative to the vegetable gum (ii) comprised from 2: 1 to 1 :2, preferably 1 : 1.

As regards the mixture contained in the composition of the present invention, said mixture contains the bacterial strains (i), said vegetable gum (ii) and said bacterial strains (iii) in a weight ratio of 1 :1 : 1 , or 2: 1 :2. The above-cited bacterial strains (i) and (iii) are present in the composition of the present invention in an amount comprised from 0.1 to 50% by weight, preferably from 0.5 to 15% by weight, even more preferably from 1 to 10%, relative to the total weight of the composition or supplement product. However, said percentage is based on the kind of the intended pharmaceutical form to be produced. For example, in the case of capsules the amount of said bacteria is greater than 30%, for example greater than 35%. In an embodiment, the composition comprises a mixture of bacterial strains at a concentration comprised from 1x10⁶ to 1x10¹¹ CFU/g, preferably from 1x10⁸ to 1x10¹⁰ CFU/g of mixture or single bacterial strain.

In an embodiment, the composition comprises bacterial strains at a concentration comprised from 1x10^s to 1x10¹¹ CFU/dose, preferably from 1x10⁸ to 1x10¹⁰ CFU/dose. The dose can be from 0.2 to 10 g, for example can be 0.25 g, 1 g, 3 g, 5 g or 7 g. Bacterial strains can be present in the composition in a solid form, for example in the form of powder, dry powder, or freeze-dried powder.

The composition of the present invention is for oral use and for the treatment of an autoimmune disorder, or disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 -IL-17. Th17 cells are involved, by way of a non-limiting example, in psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis and chronic pelvic pain syndrome (CPPS).

Preferably, said treatment comprises the reduction of the amount of interleukins-17 (IL-17) in the treated subject. Preferably, said autoimmune disorder or disease or systemic inflammatory disease is selected from psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, particularly noninfectious uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS). More preferably, said autoimmune disease is selected from asthma, psoriasis, rheumatoid arthritis, even more preferably said autoimmune disease is psoriasis.

It is an object of the present invention some pharmaceutical compositions or a composition for medical devices, or a composition for supplement products or a composition for food products for the preventive or curative treatment of an autoimmune disorder or disease or systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 -IL-17. Th17 cells are involved, by way of a non-limiting example, in psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis and chronic pelvic pain syndrome (CPPS).

Preferably, said treatment comprises the reduction of interleukins-17 (IL-17) in the treated subject. Preferably, said autoimmune disorder or disease or systemic inflammatory disease is selected from psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, particularly noninfectious uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS). More preferably, said autoimmune disease is selected from asthma, psoriasis, rheumatoid arthritis, even more preferably said autoimmune disease is psoriasis.

The composition of the present invention is in a solid, liquid, semiliquid or powdery form and can be formulated by using the suitable technological additives or co-formulants, pH stabilizers, dispersants, flavors and excipients of pharmaceutical grade for oral administration in the form of tablet, lozenge, capsule, packet or stick.

In vitro studies

The Applicant conducted several tests and experiments on a first wide group of both lactic bacteria and bifidobacteria strains thus obtaining, after careful selections, a second group of lactic bacteria (Table 1) and bifidobacteria (Table 2) more effective in reducing IL-17 or IL-17A (rather than inhibiting the production of IL-17 or IL-17A) to an extent in which IL-17 keeps and maintains its protective function against infections. These tests and experiments were conducted in order to obtain said second selection of bacterial strains (iii).

In the present in vitro study, conducted at the laboratories Biolab Research-Mofin Alee Group, the ability of several bacterial strains to modulate, after 5-day stimulation, the secretion of the human cytokine IL-17A was assessed.

1. METHOD

1.1 Bacterial cultures and growth conditions

In the present in vitro study a number of bacterial strains (Tables 1 and 2), all belonging to the Probiotical SpA's collection, were used. The different strains were cultured in Man Rogosa Sharpe (MRS) medium, supplemented, for bifidobacteria only, with 0.05% L-cysteine (Sigma Chemical), in a thermostatic bath at specific temperatures for each strain (range 30-37°C). As regards the immunomodulation experiments, following to a growth period of about 16 hours, bacteria were subcultured for 6 hours, under the above- cited conditions, in order to achieve the exponential growth phase. They were thus washed twice with sterile phosphate-buffered saline (PBS, pH 7.2); the physiological condition and the cell number were determined by a cytofluorimetric technique by using the commercial kit "Cell Viability Kit with liquid beads", marketed by Becton Dickinson, following the producer's instructions. Cell were thus brought to the optimum concentration determined in previous experiments and used in subsequent tests.

Table 1

L. fermentum LF09 1462 DSM 18298

L. fermentum LF10 1637 DSM 19187

L. fermentum LF11 1639 DSM 19188

L plantarum LP01 1171 LMG P-21021

L. plantarum LP02 91 LMG P-21020

L. reufer/ LRE01 1775 DSM 23877

L. reuteri LRE02 1774 DSM 23878

L. reuteri LRE03 1777 DSM 23879

L. reuteri LRE04 1779 DSM 23880

L. reuteri DL LRE07 1848 DSM 25683

L reuten^' DL LRE08 1841 DSM 25684

L reuteri DL LRE09 1842 DSM 25685

L salivarius LS01 1797 DSM 22775

L salivarius LS02 1468 DSM 32204

L salivarius LS03 1382 DSM 22776

L salivarius LS05 1719 DSM 26036

L salivarius LS06 1727 DSM 26037

L salivarius DLV1 1806 DSM 25138

L salivarius DLV8 1813 DSM 25545

Table 2 Internal Identification Deposit number

Strain name - Probiotical abbreviation

Code (ID) International collection

B. animalis subsp lactis BS01 1195 LMG P-21384

B. breve BR03 1270 DSM 16604

B. lactis BA05 1518 DSM 18352

B. longum BL01 1293 DSM 28173

B. longum BL02 1295 DSM 28174

B. longum BL03 1152 DSM 16603

B. longum BL04 1740 DSM 23233

B. longum BL05 1352 DSM 23234

B. longum BL06 N.A. DSM 24689

B. longum W11 1114

S. /ongw? W11wt 1161

S. /ongum PCB133 1687 DSM 24691

B. longum B1975 1742 DSM 24709

S. longum DLBL08 1823 DSM 25670 a longum DLBL10 1824 DSM 25672 a pseudolongum subsp. globosum BPS01 1812 DSM 26456

1.2 Separation of peripheral blood mononuclear cells

Peripheral blood mononuclear cells (PBMC) comprise cells involved both in natural and specific immunity, and are a valid model for studying the immunological properties of potential probiotic bacteria, in particular for the analysis of cytokine secretion. Peripheral blood mononuclear cells (PBMC) were separated by density gradient centrifugation. For this purpose for each experiment 20 ml of "buffy coat" of healthy donors from the Immuno-transfusion Service of Ospedale di Borgomanero were used, thus obtaining an average yield of 200 x 10⁶ PBMC/buffy. The amount of separated cells was determined by cell counting in Burker chambers, by using the Turk's solution, which allows to discriminating between mononuclear cells and polymorphonuclear cells. Cells were brought to a concentration of 2 x 10⁶ cells/ml in growth medium RPMI-1640 (Invitrogen) supplemented with 10% heat-inactivated fetal calf serum (FCS, Gibco), 1% glutamine and 25 mM Hepes.

1.3 PBMC stimulation with bacterial strains

After separation, PBMCs were stimulated for 5 days with all the bacterial strains listed in Tables 1 and 2. The internal controls for each experiment are represented by:

Negative control: PBMC alone

Positive control: PBMC stimulated with 10 pg/ml Phytohaemagglutinin (PHA-P; Sigma

Chemicals Co., St. Louis, MO).

At the end of stimulation, cultures were centrifuged at 1500 rpm for 10 minutes. Supernatants were taken and stored at -20°C until analysis.

1.4 Cytokine assay

Cytokine concentration in the culture supernatants was determined by E.L.I.S.A. assay (Enzyme-Linked Immunoabsorbent Assay). Specifically, for the IL-17A assay the kit "Human ELISA Ready-SET-Go!" from eBioscence, (San Diego CA) was used, following the producer's instructions. KIT sensitivity: 4 pg/ml. 2. RESULTS

2.1 Interleukin 17 modulation

The different spectrum of cytokines secreted by cell subpopulations involved in the immune responses plays a main role in selecting the kind of effector system, which should be used in response to a particular antigenic stimulus. Lymphocytes T are the main effector and regulatory cells of the cell-mediated immunity. As a response to an antigen or pathogen, T cells synthesize and secrete a variety of cytokines required for the growing, differentiation and as activation factors for the other immunocompetent cells. In order to investigate whether the studied bacterial strains could inhibit the secretion of cytokine IL-17A by human PBMCs, such cells were co-cultured with bacteria for 5 days. The amount of cytokine, released in the culture supernatants, was determined by E.L.I.S.A assay.

As shown in Figure 1 , 14 of the 22 different studied bacterial strains, all belonging to the genus Lactobacillus (Table 1), showed to be able to inhibiting the secretion of the investigated cytokine. As regards bacteria belonging to the genus Bifidobacterium (Table 2), only 6 of them shown an equal ability (Figure 2). In order to study whether the inhibitory action on IL-17 was a peculiarity of either the species or bacterial strain, a comparison by using strains belonging to the same species was made. As shown in Figures 1 B and 1C, reporting data concerning the species L. reuteri and L. salivarius, respectively, it is clear that modulation of IL-17A is not typical of the species, but strain-related. Similar results were obtained by using bacterial strains of B. longum, (Figure 2).

The comparison of the results of strains, which inhibited the IL-17 secretion, demonstrated that the bacterial strains, with a greater inhibitory ability, belong to the species L. plantarum (n=1 ; inhibition 57%), L. reuteri (n=4; DL LRE09 46%; overall inhibition range: 14-46%) and L. salivarius (n=5; LS03 54%; LS06 57%; overall inhibition range: 19-57%) (Figure 3). By contrast, the analysis of the strains of Bifidobacteria did not allow to select strains with marked inhibitory properties (20-25% inhibition for all the studied strains) (Figure 4).

Figure 1 shows the modulation of interleukin 17 by strains belonging to the genus Lactobacillus.

The analysis was conducted on culture supernatants after 5 days of bacterial stimulation. Values, being expressed as percentage, represent:

Horizontal bold line: Mean of 8 independent experiments. Box of the experimental data range (minimum- maximum). Box under the dotted line (basal, no stimulation)→ cytokine inhibition; box above the dotted line (basal, no stimulation)→ cytokine induction.

Figure 2 shows the modulation of interleukin 17 by strains belonging to the genus Bifidobacterium.

Figure 3 shows the strains with inhibitory ability belonging to the genus Lactobacillus. The analysis was conducted on culture supernatants after 5 days of bacterial stimulation. Values, being expressed as percentage, represent:

Figure 4 reports the strains with inhibitory ability belonging to the genus Bifidobacterium. The analysis was conducted on culture supernatants after 5 days of bacterial stimulation. The values, being expressed as percentage, represent:

Horizontal bold line: Mean of 8 independent experiments. Box of the experimental data range (minimum- maximum). Box under the dotted line (basal, no stimulation)→ cytokine inhibition; box above the dotted line (basal, no stimulation)→ cytokine induction. In the present study, the effect of some strains on the inhibition of interleukin 17 secreted by human PBMCs was assessed. Data allowed the selection of some strains, belonging to both the genus Lactobacillus and Bifidobacterium, able to inhibiting the IL-17 secretion (L plantarum LP01 57%; L. reuteri DL LRE09 46%; L. salivarius LS03 54%; L. salivarius LS06 57%; Bifidobacteria range 20-25%).

The detailed procedure used in the above-cited method with reference to the present in vitro study is described below.

All the samples and reagents used in the above method were brought to room temperature of 25°C prior to their use. All the steps described below were carried out at 25°.

(i) Taking a number of flat-bottom 96-well plates, specific for E.L.I.S.A. assays (Corming Costar 9018 ELISA, included in the kit), so that to have one well for each sample to be tested and a sufficient number of wells for preparing the standard calibration curve (16 wells in total).

(ii) Diluting 250 times a stock solution of primary antibody (Capture Ab; final concentration 10 pg/ml) in the coating solution 1X (stock solution 10X, included in the kit, to be diluted 1 :10 in sterile distilled water).

(iii) Dispensing 100 μΙ of such a solution in all the wells; coating the plate with an adhesive strip, and incubating overnight (O.N.) at 4°C (refrigerator).

(iv) Washing 5 times each well with 200 μΙ of washing solution (0.05% Tween 20 in PBS). By using a vacuum pump, sucking the liquid from the last wash in all the wells and inverting the plate over an absorbent paper sheet for the removal of any remaining solution.

(v) Adding 200 μΙ of assay buffer 1X (stock solution 5X, included in the Kit, to be diluted 1 :5 in sterile distilled water) to all the wells and incubating for 1 hour at room temperature (RT).

(vi) Washing 5 times each well with 200 μΙ of washing solution. By using a vacuum pump, sucking the liquid from the last wash in all the wells and inverting the plate over an absorbent paper sheet for the removal of any remaining solution.

(vii) Preparing the solution containing the recombinant human cytokine, required for the standard calibration curve, following the table below, centrifuging all the tubes before their opening:

Cytokine: IL-17A; curve range 8 points: 4-500; curve dilution: 1 :2; stock 5 1; buffer: 10 ml.

(viii) Serially diluting according to the scheme reported in Figure 5, dispensing 100 μΙ of assay buffer 1X in C2-C8 wells. Dispensing 200 μΙ of STOCK (prepared according to the previous table) in well Ci and proceeding with the serial dilutions 1 :2 as reported in the scheme (Fig. 5). Dilutions can be directly done in the wells or in eppendorf tubes. The curve should be prepared in duplicate.

(ix) Adding 100 μΙ of each sample to be dosed (S, in duplicate) in the corresponding well according to the scheme of the plate. Covering the plate with the adhesive strip and incubating over night (O.N.) at 4°C (refrigerator).

(x) Preparing the solution containing the biotinylated secondary antibody (detection Ab), by diluting 250 times the stock solution in Assay buffer 1X, following the manufacturer's instructions. (xi) Washing 5 times each well with 200 μΙ of washing solution. By using a vacuum pump, sucking the liquid from the last wash in all the wells and inverting the plate over an absorbent paper sheet for the removal of any remaining solution.

(xii) Dispensing 100 μΙ of solution containing the secondary Ab in all the wells, coating the plate with the adhesive strip, and incubating for 1 hour at RT.

(xiii) Preparing the solution containing the enzyme Avidin-HRP, by diluting 250 times the stock solution in Assay buffer 1X, as reported in the manufacturer's instructions.

(xiv) Washing 5 times each well with 200 μΙ of washing solution. By using a vacuum pump, sucking the liquid from the last wash in all the wells and inverting the plate over an absorbent paper sheet for the removal of any remaining solution.

(xv) Dispensing 100 μΙ of enzyme solution in all the wells, coating the plate with the adhesive strip and incubating 30 min a RT.

(xvi) Washing 7 times each well with 200 μΙ of washing solution. By using a vacuum pump, sucking the liquid from the last wash in all the wells and inverting the plate over an absorbent paper sheet for the removal of any remaining solution.

(xvii) Adding 100 μΙ of Substrate (1X TMB solution) in all the wells and incubating at RT for 10 minutes in the dark (cover the plate with aluminum foil).

(xviii) Stopping the reaction by adding 50 μΙ of sulfuric acid 2N in all the wells (the color will turn from light blue to yellow).

(xix) Reading the plate with a spectrophotometric reader suitable for 96-well plates within 30 min from the development at a wavelength of 450 nm.

(xx) Proceeding with the reading of the absorbance values in the spectrophotometer in duplicate (standard and samples) and preparing the relative curves in order to calculate the amounts/concentrations of IL-17A.

Claims

1. Composition comprising a mixture, which comprises or, alternatively, consists of:

(i) a first selection of bacterial strains, said bacterial strains producing in situ in the gastrointestinal tract bacterial gums such as exopolysaccharides (briefly, EPS), once administered, and being selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species selected from the group comprising or, alternatively, consisting of the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus;

(ii) vegetable gums, and

(iii) a second selection of bacterial strains, said bacterial strains being selected from the group comprising or, alternatively, consisting of bacterial strains belonging to the species Lactobacillus salivarius;

said composition being for use in the preventive or curative treatment of an autoimmune or neurodegenerative disorder or disease or a systemic inflammatory disease due to a dysregulation of the immune system, which reacts by overproducing interleukins-17 (IL-17, IL-17A) wherein said autoimmune or neurodegenerative disease or systemic inflammatory disease is selected from the group comprising or, alternatively, consisting of psoriasis, rheumatoid arthritis, Crohn's disease, multiple sclerosis, asthma, epilepsy, cerebral ischemia, lupus erythematosus, uveitis, autoimmune prostatitis and chronic pelvic pain syndrome (CPPS).

2. The composition for use according to claim 1, said composition being for use in the preventive or curative treatment of psoriasis.

3. The composition for use according to claim 1 or 2, wherein said first selection of bacterial strains (i) comprises bacterial strains belonging to the species Streptococcus thermophilus.

4. The composition for use according to claim 3, wherein said bacterial strains (i) belonging to the species Streptococcus thermophilus are selected from the group comprising or, alternatively, consisting of:

- Streptococcus thermophilus DSM 25247 (ST11) deposited at the DSMZ institute in Germany on 19/09/2011 , - Streptococcus thermophilus DSM 25282 (ST12) deposited at the DSMZ institute in Germany on 20/10/2011.

5. The composition for use according to any one of claims 1-4, wherein said vegetable gum (ii) is selected from the group comprising or, alternatively, consisting of Aloe, Aloe vera, Aloe arborescens and tara gum; preferably is a tara gum.

6. The composition for use according to any one of claims 1-5, wherein the bacterial strain (i) belonging to the species Streptococcus thermophilus is Streptococcus thermophilus DSM 25246 (ST10) deposited at the DSMZ institute in Germany on 19/09/2011 , and said vegetable gum (ii) is a tara gum.

7. The composition for use according to any one of claims 1-6, wherein said second selection of bacterial strains (iii) comprises bacterial strains belonging to the species Lactobacillus salivarius which are selected from the group comprising or, alternatively, consisting of:

(a) Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical S.p.A.,

(b) Lactobacillus salivarius DSM 32204 (LS02), deposited on 13/11/2015 at the DSMZ institute by Probiotical SpA.,

(c) Lactobacillus salivarius DSM 22776 (LS03), deposited on 23/07/2009 at the DSMZ institute by Probiotical SpA.,

(d) Lactobacillus salivarius DSM 26037 (LS06), deposited on 06/06/2012 at the DSMZ institute by Probiotical SpA.,

8. The composition for use according to any one of claims 1-7, wherein said bacterial strains (iii) are selected from the group comprising or, alternatively, consisting of:

(a) Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical S.p.A,

(e) Lactobacillus salivarius DSM 29476 (LS07), deposited on 09/10/2014 at the DSMZ institute by Probiotical SpA,

(f) Lactobacillus plantarum LMG P-21021 (LP01), deposited on 16/10/2001 at the BCCM LMG institute by Mofin S.r.l., (g) Lactobacillus reuteri DSM 23880 (LRE04), deposited on 05/08/2010 at the DSMZ institute by Probiotical SpA,

(I) Bifidobacterium breve DSM 29494 (BR05), deposited on 09/10/2014 at the DSMZ institute by Probiotical SpA.

9. The composition for use according to any one of claims 1-8, wherein the bacterial strain (i) belonging to the species Streptococcus thermophilus is Streptococcus thermophilus DSM 25246 (ST10) deposited at the DSMZ institute in Germany on 19/09/2011 , said vegetable gum (ii) is a tara gum and the bacterial strain (iii) is Lactobacillus salivarius DSM 22775 (LS01), deposited on 23/07/2009 at the DSMZ institute by Probiotical S.p.A.