OA18795A

OA18795A - Compositions comprising bacterial strains.

Info

Publication number: OA18795A
Application number: OA1201800179
Authority: OA
Inventors: Imke Elisabeth MULDER; Amy Beth HOLT; Seanin Marie MCCLUSKEY; Grainne Clare LENNON; Suaad AHMED
Original assignee: 4D Pharma Research Limited
Priority date: 2015-11-23
Filing date: 2016-11-23
Publication date: 2019-06-28

Abstract

The invention provides compositions comprising bacterial strains for treating and preventing inflammatory and autoimmune diseases.

Description

COMPOSITIONS COMPRISING BACTERIAL STRAINS

TECHNICAL FIELD

This invention is in the field of compositions comprising bacterial strains isolated from the mammalian digestive tract and the use of such compositions in the treatment of disease.

BACKGROUND TO THE INVENTION

The human intestine is thought to be stérile in utero, but it is exposed to a large variety of maternai and environmental microbes immediately after birth. Thereafter, a dynamic period of microbial colonization and succession occurs, which is influenced by factors such as delivery mode, environment, diet and host génotype, ail of which impact upon the composition of the gut microbiota, particularly during early life, Subsequently, the microbiota stabtlizes and becomes adult-like [1], The human gut microbiota contains more than 500-1000 different phylotypes belonging essentially to two major bacterial divisions, the Bacteroidetes and the Firmicutes [2]. The successful symbiotic relationships arising from bacterial colonization of the human gut hâve yielded a wide variety of metabolic, structural, protective and other bénéficiai fiinctions. The enhanced metabolic activities of the colonized gut ensure that otherwise indigestible dietary components are degraded with release of by-products providing an important nutrient source for the host. Simîlarly, the îmmunological importance of the gut microbiota is well-recognized and is exemplified in germfree animais which hâve an impaired immune system that is functionally reconstituted following the introduction of commensal bacteria [3-5].

Dramatic changes in microbiota composition hâve been documented in gastrointestinal disorders such as inflammatory bowel disease (IBD). For example, the levels of Clostridium cluster XlVa bacteria are reduced in IBD patients whilst numbers of E. coli are increased, suggesting a shift in the balance of symbionts and pathobionts within the gut [6-9], Interestingly, this microbial dysbiosis is also associated with imbalances in T effector cell populations.

In récognition of the potential positive effect that certain bacterial strains may hâve on the animal gut, various strains hâve been proposed for use in the treatment of various diseases (see, for example, [10-13]). Also, certain strains, including mostly Lactobacillus and Bifidobacterium strains, hâve been proposed for use in treating various inflammatory and autoimmune diseases that are not directly linked to the intestines (see [14] and [15] for reviews). However, the relationship between different diseases and different bacterial strains, and the précisé effects of particular bacterial strains on the gut and at a systemic level and on any particular types of diseases, are poorly characterised.

Cell wall fragments from Streptococcus pyogeues, Lactobacillus casei and various strains of Eubacterium, including E. contortum, hâve been found to induce chronic polyarthritis and joint inflammation (see [ 16]).

There is a requirement in the art for new methods of treating inflammatory and autoimmune diseases. There is also a requirement for the potential effects of gut bacteria to be characterised so that new thérapies using gut bacteria can be developed.

SUMMARY OF THE INVENTION

The inventors hâve developed new thérapies for treating and preventing inflammatory and autoimmune diseases. In particular, the inventors hâve developed new thérapies for treating and preventing diseases and conditions mediated by IL-17 or the Thl7 pathway. In particular, the inventors hâve identified that bacterial strains from the genus Eubacterium can be effective for treating and preventing diseases and conditions mediated by IL-17 or the Thl7 pathway. As 10 described in the examples, oral administration of compositions comprising Eubacterium contortum may reduce the severity of the inflammatory response, including the Thl7 inflammatory response, in mouse models of uveitis.

Therefore, in a first embodiment, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing a disease or condition 15 mediated by IL-I7 or the Thl7 pathway. The inventors hâve identified that treatment with bacterial strains from this species can provide clinical benefits in mouse models of inflammatory and autoimmune diseases mediated by IL-l 7 and the Thl7 pathway, may reduce levels of cytokines that are part of the Thl7 pathway, including IL-17, and may alleviate the Thl7 inflammatory response.

In particular embodiments, the invention provides a composition comprising a bacterial strain of the 20 genus Eubacterium, for use in a method of treating or preventing a disease or condition selected from the group consisting of: uveitis; cancer, such as breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer; multiple sclerosis; arthritis, such as rheumatoid arthritis, osteoarthritis, psoriatic arthritis, or juvénile idiopathic arthritis; neuromyelitis optica (Devic's disease); ankylosing spondylîtis; spondyloarthritis; psoriasis; systemic lupus erythematosus; inflammatory bowel disease, 25 such as Crohn’s disease or ulcerative colitis; celiac disease; asthma, such as allergie asthma or neutrophilie asthma; chrome obstructive pulmonary disease (COPD); scleritis; vasculitis; Behcefs disease; atherosclerosis; atopie dermatitis; emphysema; periodontitis; allergie rhinitîs; and allograft rejectîon. The effect shown for the bacterial strains from the genus Eubacterium on the Thl7 inflammatory response and on diseases mediated by IL-17 and the Thl7 pathway may provide 30 therapeutic benefits for other diseases and conditions mediated by IL-17 and the ThI7 pathway, such as those listed above.

In particularly preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing uveitis, such as posterior uveitis. The inventors hâve identified that treatment with Eubacterium strains can reduce 35 disease incidence and disease severity in a mouse model of uveitis and can prevent or reduce retinal damage. In preferred embodiments, the invention provides a composition comprising a bacterial strain of the species Eubacterium contortum, for use in the treatment of uveitis. Compositions using Eubacterium contorlum may be particularly effective for treating uveitis.

In further preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing asthma, such as neutrophilie asthma or allergie asthma. Treatment with Eubacterium strains may reduce recruitment of neutrophils and eosinophils into the lungs, which can help treat or prevent asthma. In certain embodiments, the composition is for use in a method of treating or preventing neutrophilie asthma or éosinophilie asthma. The compositions of the invention may be particularly effective for treating or preventing neutrophilie asthma and éosinophilie asthma. Indeed, in certain embodiments, the composition is for use in a method of reducing a neutrophilie inflammatory response in the treatment or prévention of asthma, or the composition is for use in a method of reducing an éosinophilie inflammatory response in the treatment or prévention of asthma. In preferred embodiments, the invention provides a composition comprising a bacterial strain of the species Eubacterium contortum for use in the treatment of asthma, and in particular éosinophilie or allergie asthma. Also, Eubacterium contortum may hâve a particularly pronounced effect on neutrophils in asthma models and treatment with Eubacterium contortum may be particularly effective for treating neutrophilie asthma.

In further preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing rheumatoid arthritis. Treatment with Eubacterium strains may provide clinical benefits in a mouse model of rheumatoid arthritis and reduce joint swelling. In preferred embodiments, the invention provides a composition comprising a bacterial strain of the species Eubacterium contortum, for use in the treatment of rheumatoid arthritis. Compositions using Eubacterium contortum may be particularly effective for treating rheumatoid arthritis.

In further preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing multiple sclerosis. Treatment with Eubacterium strains may reduce disease incidence and disease severity in a mouse model of multiple sclerosis. In preferred embodiments, the invention provides a composition comprising a bacterial strain of the species Eubacterium contortum, for use in the treatment of multiple sclerosis. Compositions using Eubacterium contortum may be particularly effective for treating multiple sclerosis.

In further preferred embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for use in a method of treating or preventing cancer, such as breast, lung or liver cancer. Compositions comprising a bacterial strain of the genus Eubacterium may reduce tumour growth in mouse models of breast, lung and liver cancer. In certain embodiments, the composition is for use in a method of reducing tumour size or preventing tumour growth in the treatment of cancer. In certain embodiments, the invention provides a composition comprising a bacterial strain of the species Eubacterium contortum, for use in the treatment of cancer.

In certain embodiments, the compositions of the invention are for use in a method of reducing IL-l 7 production or reducing Thl7 cell différentiation in the treatment or prévention of a disease or condition mediated by IL-l7 or the Thl7 pathway. In particular, the compositions of the invention may be used in reducing IL-l7 production or reducing Thl7 cell différentiation in the treatment or prévention of asthma, rheumatoid arthritis, multiple sclerosis, uveitis or cancer. Preferably, the invention provides compositions comprising a bacterial strain of the genus Eubacterium contortum. for use in reducing IL-l7 production or reducing Thl7 cell différentiation in the treatment or prévention of asthma, rheumatoid arthritis, multiple sclerosis, uveitis or cancer.

In certain embodiments, the composition is for use in a patient with elevated IL-l7 levels or Th17 cells. The effect shown for Eubacterium strains on uveitis, which is strongly associated with the Thl7 inflammatory response, means that Eubacterium strains may be particularly bénéficiai for such patients.

In preferred embodiments of the invention, the bacterial strain in the composition is of Eubacterium contortum. Closely related strains may also be used, such as bacterial strains that hâve a I6s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the I6s rRNA sequence of a bacterial strain of Eubacterium contortum. Preferably, the bacterial strain has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: 1, 2, 3 or 4. Preferably, the sequence identity is to SEQ ID NO:4. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:4.

In certain embodiments, the composition of the invention is for oral administration. Oral administration of the strains ofthe invention can be effective for treating IL-17- or Thl7 pathwaymediated diseases and conditions. Also, oral administration is convenient for patients and practitioners and allows delivery to and / or partial or total colonisation of the intestine.

In certain embodiments, the composition of the invention comprises one or more pharmaceutîcally acceptable excipients or carriers.

In certain embodiments, the composition of the invention comprises a bacterial strain that has been lyophilised. Lyophilisation is an effective and convenient technique for preparing stable compositions that allow delivery of bacteria.

In certain embodiments, the invention provides a food product comprising the composition as described above.

In certain embodiments, the invention provides a vaccine composition comprising the composition as described above.

Additionally, the invention provides a method of treating or preventing a disease or condition mediated by IL-17 or the Thl7 pathway, comprising administering a composition comprising a bacterial strain of the genus Eubacterium.

In developing the above invention, the inventors hâve identified and characterised a bacterial strain that is particularly useful for therapy. The Eubacterium contortum strain of the invention is shown to be effective for treating the diseases described herein, such as uveitis. Therefore, in another aspect, the invention provides a cell of the Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689), or a dérivative thereof. The invention also provides compositions comprising such cells, or biologically pure cultures of such cells. The invention also provides a cell of Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689), or a dérivative thereof, for use in therapy, in particular for the diseases described herein.

BRIEF DESCRIPTION OF DRAWINGS

Figure 1: Mouse model of uveitis - TEFI Scores in the control group. Data are presented as Mean ± SEM.

Figure 2: Mouse model of uveitis - TEFI Scores on Day 28. Data are presented as Mean ± SEM.

DISCLOSURE OF THE INVENTION

Bacterial strains

The compositions of the invention comprise a bacterial strain of the genus Eubacterium. The examples demonstrate that bacteria of this genus are useful for treating or preventing uveitis and diseases and conditions mediated by IL-17 or the Th 17 pathway. The preferred bacterial strains are of the species Eubacterium contortum.

The invention provides a Eubacterium, for example, a Eubacterium contortum for use in therapy, for example, for use in treating or preventing an inflammatory and/or autoimmune disease. Similarly, the invention provides a composition comprising a bacterial strain of the genus Eubacterium, for example, a Eubacterium contortum, for use in therapy, for example, for use in treating or preventing an inflammatory and/or autoimmune disease. In certain embodiments, the compositions of the invention comprise Eubacterium. for example, a Eubacterium contortum, and do not contain any other bacterial genus. In certain embodiments, the compositions of the invention comprise a single species of Eubacterium, for example, a Eubacterium contortum, and do not contain any other bacterial species. In certain embodiments, the compositions of the invention comprise a single strain of Eubacterium, for example, of Eubacterium contortum and do not contain any other bacterial strains or species.

Examples of Eubacterium species for use in the invention include Eubacterium contortum, Eubacterium fissicatena, Eubacterium limosum, Eubacterium rectale and Eubacterium aerofaciens. Eubacterium are gram positive, obligately anaérobie, non-spore-forming rods which do not produce propionic acid or lactic acid as a major acid product [17], The type strain of Eubacterium contortum is ATCC 25540 = DSM 3982 [l 7], GenBank accession numbers for the 16S rRNA gene sequence for Eubacterium contortum strain DSM 3982 are FR749945, FR749946 and L34615 (disclosed herein as SEQ ID NO: l-3). Exemplary Eubacterium contortum strains are described in [ 17],

In some embodiments, the Eubacterium species for use in the invention is not Eubacterium ventriosuni. In some embodiments, the Eubacterium species for use in the invention is not Eubacterium eligens. In some embodiments, a composition for use in the invention does not comprise Eubacterium ventriosum. In some embodiments, a composition for use in the invention does not comprise Eubacterium eligens.

The Eubacterium contortum bacterium tested in the Examples is referred to herein as strain MRX050. A 16S rRNA sequence for the MRX050 strain that was tested is provided in SEQ ID NO:4. Strain MRX050 was deposited with the international depositary authority NCIMB, Ltd. (Ferguson Building, Aberdeen, AB2I 9YA, Scotland) by 4D Pharma Research Ltd. (Life Sciences Innovation Building, Aberdeen, AB25 2ZS, Scotland) on I5th November 2016 and was assigned accession number NCIMB 42689. The terms “MRX050” and “MRx0050 are used interchangeably herein.

Bacterial strains closely related to the strain tested în the examples are also expected to be effective for treating or preventing uveitis and diseases and conditions mediated by IL-I7 or the Thl7 pathway. In certain embodiments, the bacterial strain for use in the invention has a 16s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to the 16s rRNA sequence of a bacterial strain of Eubacterium contortum. Preferably, the bacterial strain for use in the invention has a I6s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: l, 2, 3 or 4. Preferably, the sequence identity is to SEQ ID NO:4. Preferably, the bacterial strain for use in the invention has the 16s rRNA sequence represented by SEQ ID NO:4.

Bacterial strains that are biotypes of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) and ATCC 25540 are also expected to be effective for treating or preventing uveitis and diseases and conditions mediated by IL-17 or the Thl7 pathway. A biotype is a closely related strain that has the same or very similar physiological and biochemical characteristics.

Strains that are biotypes of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 and that are suitable for use in the invention may be identified by sequencing other nucléotide sequences for strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540. For example, substantially the whole genome may be sequenced and a biotype strain for use in the invention may hâve at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity across at least 80% of its whole genome (e.g. across at least 85%, 90%, 95% or 99%, or across its whole genome). For example, in some embodiments, a biotype strain has at least 98% sequence identity across at least 98% of its genome or at least 99% sequence identity across 99% of its genome. Other suitable sequences for use in identifying biotype strains may include hsp60 or répétitive sequences such as BOX, ERIC, (GTGL, or REP or [I8]. Biotype strains may hâve sequences with at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to the corresponding sequence of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540. In some embodiments, a biotype strain has a sequence with at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to the corresponding sequence of strain MRX050 deposited as NCIMB 42689 and comprises a 16S rRNA sequence that is at least 99% identical (e.g. at least 99.5% or at least 99.9% identical) to SEQ ID NO:4. In some embodiments, a biotype strain has a sequence with at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% sequence identity to the corresponding sequence of strain MRX050 deposited as NCIMB 42689 and has the 16S rRNA sequence of SEQ ID NO:4.

Alternatively, strains that are biotypes of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 and that are suitable for use in the invention may be identified by using strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 and restriction fragment analysis and/or PCR analysis, for example by using fluorescent amplified fragment length polymorphism (FAFLP) and répétitive DNA element (rep)-PCR fïngerprinting, or protein profîling, or partial 16S or 23s rDNA sequencing. In preferred embodiments, such techniques may be used to identify other Eubacterium contortum strains.

In certain embodiments, strains that are biotypes of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 and that are suitable for use in the invention are strains that provide the same pattern as strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 when analysed by amplified ribosomal DNA restriction analysis (ARDRA), for example when using Sau3AI restriction enzyme (for exemplary methods and guidance see, for example,[l9]). Alternatively, biotype strains are identified as strains that hâve the same carbohydrate fermentation patterns as strains MRX050 (în particular MRX050 deposited as NCIMB 42689) or ATCC 25540.

Other Eubacterium contortum strains that are useful in the compositions and methods of the invention, such as biotypes of strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540, may be identified using any appropriate method or strategy, including the assays described in the examples. For instance, strains for use in the invention may be identified by culturing in anaérobie YCFA and/or administering the bacteria to the type II collagen-induced arthritîs mouse model and then assessing cytokine levels. In particular, bacterial strains that hâve simîlar growth patterns, metabolic type and/or surface antigens to strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540 may be useful in the invention. A useful strain will hâve comparable immune modulatory activity to strains MRX050 (in particular MRX050 deposited as NCIMB 42689) or ATCC 25540. In particular, a biotype strain will elicit comparable effects on the uveitis disease models to the effects shown in the Examples, which may be identified by using the culturing and administration protocols described in the Examples.

A particularly preferred strain of the invention is strain MRX050 strain (in particular MRX050 deposited as NCIMB 42689). This is the exemplary strain tested in the examples and shown to be effective for treating disease. Therefore, the invention provides a cell, such as an isolated cell, of Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689), or a dérivative thereof. The invention also provides a composition comprising a cell of Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689), or a dérivative thereof. The invention also provides a biologically pure culture of Eubacterium contortum strain MRX050 (în particular MRX050 deposited as NCIMB 42689). The invention also provides a cell of Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689), or a dérivative thereof, for use in therapy, in particular for the diseases described herein. A dérivative of Eubacterium contortum strain MRX050 (in particular MRX050 deposited as NCIMB 42689) may be a daughter strain (progeny) or a strain cultured (subcloned) from the original.

A dérivative of a strain of the invention may be modified, for example at the genetic level, without ablating the biological activity. In particular, a dérivative strain of the invention is therapeutically active. A dérivative strain will hâve comparable immune modulatory activity to the Eubacterium contortum strain MRX050 (în particular MRX050 deposited as NCIMB 42689). In particular, a dérivative strain will elicit comparable effects on the uveitis disease models to the effects shown in the Examples, which may be identified by using the culturing and administration protocols described în the Examples. A dérivative of strain MRX050 (in particular MRX050 deposited as NCIMB 42689) will generally be a biotype of strain MRX050 (in particular MRX050 deposited as NCIMB 42689).

References to cells of Eubacterium contortum strain MRX050 encompass any cells that hâve the same safety and therapeutic efficacy characteristics as strain MRX050, and such cells are encompassed by the invention. Reference to MRX050 deposited as NCIMB 42689 refers to the deposited MRX050 strain only.

In preferred embodiments, the bacterial strains in the compositions of the invention are viable and capable of partially or totally colonising the intestine.

Therapeutic uses

As demonstrated in the examples, the bacterial compositions of the invention are effective for reducing the Thl 7 inflammatory response. In particular, treatment with compositions of the invention achieves clinical improvements in animai models of conditions mediated by IL-17 and the Thl 7 pathway and may achieve a réduction in 1L-17A levels and other Thl7 pathway cytokines. Therefore, the compositions of the invention may be useful for treating or preventing inflammatory and autoimmune diseases, and in particular diseases or conditions mediated by IL-I7. In particular, the compositions of the invention may be useful for reducing or preventing élévation of the IL-17 inflammatory response.

Thl 7 cells are a subset of T helper cells that produce, for example, IL-17A, IL17-F, IL-21 and IL-22. Thl7 cell différentiation and IL-17 expression may be driven by IL-23. These cytokines and others form important parts of the Thl7 pathway, which is a well-established inflammatory signalling pathway that contributes to and underlies a number of inflammatory and autoimmune diseases (as described in, for example, [20-25]). Diseases wherein the Thl7 pathway is activated are Thl7 pathway-mediated diseases. Thl7 pathway-mediated diseases can be ameliorated or alleviated by repressing the Thl7 pathway, which may be through a réduction in the différentiation of Thl7 cells or a réduction in their activity or a réduction in the level of Thl7 pathway cytokines. Diseases mediated by the Thl7 pathway may be characterised by increased levels of cytokines produced by Thl7 cells, such as IL-I7A, IL-17F, IL-21, IL-22, lL-26, lL-9 (reviewed in [26]). Diseases mediated by the Thl 7 pathway may be characterised by increased expression of Th-l7-related genes, such as Stat3 or IL-23R. Diseases mediated by the Thl7 pathway may be associated with increased levels of Thl 7 cells.

IL-17 is a pro-inflammatory cytokine that contributes to the pathogenesis of several inflammatory and autoimmune diseases and conditions. IL-17 as used herein may refer to any member of the IL-17 family, including IL-17A, IL-17B, IL-I7C, IL-17D, 1L-17E, and IL-I7F. IL-l7-mediated diseases and conditions are characterised by high expression of IL-17 and/or the accumulation or presence of IL-l7-positive cells in a tissue affected by the disease or condition. Similarly, IL-l7-mediated diseases and conditions are diseases and conditions that are exacerbated by high IL-17 levels or an increase in IL-17 levels, and that are alleviated by low IL-17 levels or a réduction in IL-17 levels. The IL-17 inflammatory response may be local or systemic.

ΙΟ

Examples of diseases and conditions that may be mediated by IL-17 or the Thl7 pathway include uveitis; cancer, such as breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer; multiple sclerosis; arthritis, such as rheumatoid arthritis, osteoarthritis, psorîatic arthritis, or juvénile idiopathic arthritis; neuromyelitis optica (Devic's disease); ankylosing spondylitis; spondyloarthritis; psoriasis; systemic lupus erythematosus; inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; celiac disease; asthma, such as allergie asthma or neutrophilie asthma; chronic obstructive pulmonary disease (COPD); scleritis; vasculitîs; Behcet's disease; atherosclerosis; atopie dermatitis; emphysema; periodontitis; allergie rhinitis; and allograft rejection. In preferred embodiments, the compositions of the invention are used for treating or preventing one or more of these conditions or diseases. In further preferred embodiments, these conditions or diseases are mediated by IL-17 or the Thl7 pathway. In some embodiments, the disease or condition treated by the invention is not colorectal cancer and/or colitis.

In some embodiments, the pathogenesis of the disease or condition affects the intestine. In some embodiments, the pathogenesis of the disease or condition does not affect the intestine. In some embodiments, the pathogenesis of the disease or condition is not localised at the intestine. In some embodiments, the treating or preventing occurs at a site other than at the intestine, In some embodiments, the treating or preventing occurs at the intestine and also at a site other than at the intestine. In certain embodiments, the disease or condition is systemic.

In certain embodiments, the compositions of the invention are for use in a method of reducing IL-17 production or reducing Thl7 cell différentiation in the treatment or prévention of a disease or condition mediated by IL-17 or the Thl7 pathway. In certain embodiments, the compositions of the invention are for use in treating or preventing an inflammatory or autoimmune disease, wherein said treatment or prévention is achieved by reducing or preventing élévation of the Thl 7 inflammatory response. In certain embodiments, the compositions of the invention are for use in treating a patient with an inflammatory or autoimmune disease, wherein the patient has elevated IL-17 levels or elevated Thl7 cells or is exhibiting a Thl7 inflammatory response. In certain embodiments, the patient may hâve been diagnosed with a chronic inflammatory or autoimmune disease or condition, or the composition of the invention may be for use in preventing an inflammatory or autoimmune disease or condition developing into a chronic inflammatory or autoimmune disease or condition. In certain embodiments, the disease or condition may not be responsive to treatment with TNF-a inhibitors. These uses of the invention may be applied to any of the spécifie disease or conditions listed in the preceding paragraph.

IL-I7 and the Thl7 pathway are often associated with chronic inflammatory and autoimmune diseases, so the compositions of the invention may be particularly useful for treating or preventing chronic diseases or conditions as listed above. In certain embodiments, the compositions are for use

H in patients with chronic disease. In certain embodiments, the compositions are for use in preventing the development of chronic disease.

The compositions of the invention may be useful for treating diseases and conditions mediated by IL17 or the Th 17 pathway and for addressîng the Th 17 inflammatory response, so the compositions of 5 the invention may be particularly usefiil for treating or preventing chronic disease, treating or preventing disease in patients that hâve not responded to other thérapies (such as treatment with TNF-α inhibitors), and/or treating or preventing the tissue damage and symptoms associated with IL17 and Th 17 cells. For example, IL-17 is known to activate matrix destruction in cartilage and bone tissue and IL-17 has an inhibitory effect on matrix production in chondrocytes and osteoblasts, so the 10 compositions of the invention may be useful for treating or preventing bone érosion or cartilage damage.

In certain embodiments, treatment with compositions of the invention provides a réduction or prevents an élévation in IL-17 levels, in particular IL-17A levels. In certain embodiments, treatment with compositions of the invention provides a réduction or prevents an élévation in TNFa, IFN-γ or 15 IL-6 levels. Such réduction or prévention of elevated levels of these cytokines may be useful for treating or preventing inflammatory and autoimmune diseases and conditions, in particular those mediated by IL-17 or the Th 17 pathway.

Uveitis

In preferred embodiments, the compositions of the invention are for use in treating or preventing 20 uveitis. The examples demonstrate that the compositions of the invention achieve a réduction in disease incidence and disease severity in an animal model of uveitis and so they may be useful in the treatment or prévention of uveitis. Uveitis is inflammation of the uvea and can resuit in retinal tissue destruction. It can present in different anatomical forms (anterior, intennediate, posterior or diffuse) and resuit from different, but related, causes, including systemic autoimmune disorders. IL-17 and 25 the Th 17 pathway are centrally involved in uveitis, so the efficacy of the compositions of the invention for treating uveitis indicates that the compositions of the invention may be particularly effective for treating and preventing diseases and conditions mediated by IL-17 or the Th 17 pathway. References [27-34] describe elevated sérum levels of interleukin-17A in uveitis patients, spécifie association of IL17A genetic variants with panuveitis, the rôle of Thl7-associated cytokines in the 30 pathogenesis of experimental autoimmune uveitis, the imbalance between Thl 7 Cells and regulatory

T Cells during monophasic experimental autoimmune uveitis, the up-regulation of IL-17A in patients with uveitis and active Adamantiades-Behçet and Vogt-Koyanagi-Harada (VKH) diseases, the treatment of non-infectious uveitis with seeukinumab (anti-lL-17A antibody), and Th 17 in uveitic eyes.

In certain embodiments, the uveitis is posterior uveitis. Posterior uveitis présents primarily with inflammation of the retina and choroid and the examples demonstrate that the compositions of the invention are effective for reducing retinal inflammation and damage.

In certain embodiments, treatment with the compositions of the invention results in a réduction in retinal damage. In certain embodiments, the compositions of the invention are for use în reducing or preventing retinal damage in the treatment of uveitis. In certain embodiments, the compositions are for use in treating patients with severe uveitis that are at risk of retinal damage. In certain embodiments, treatment with the compositions of the invention results in a réduction in optic dise inflammation. In certain embodiments, the compositions of the invention are for use in reducing or preventing optic dise inflammation. In certain embodiments, treatment with the compositions of the invention results in a réduction in retinal tissue infiltration by inflammatory cells. In certain embodiments, the compositions of the invention are for use in reducing retinal tissue infiltration by inflammatory cells. In certain embodiments, treatment with the compositions of the invention results in vision being maintained or improved. In certain embodiments, the compositions of the invention are for use in maintaining or improving vision.

In certain embodiments, the compositions are for use in treating or preventing uveitis associated with a non-infectious or autoimmune disease, such as Behçet disease, Crohn's disease, Fuchs hétérochromie iridocyclitis, granulomatosis with polyangiitis, HLA-B27 related uveitis, juvénile idiopathic arthritis, sarcoidosis, spondyloarthritis, sympathetic ophthalmia, tubulointerstitial nephritis and uveitis syndrome or Vogt-Koyanagi-Harada syndrome. IL-17A has been shown to be involved in, for example, Behçet and Vogt-Koyanagi-Harada diseases.

Treatment or prévention of uveitis may refer to, for example, an alleviation of the severity of symptoms or a prévention of relapse.

Cancer

In preferred embodiments, the compositions of the invention are for use in treating or preventing cancer. IL-l 7 and the Thl7 pathway hâve central rôles in cancer development and progression, and so the compositions of the invention may be useful for treating or preventing cancer.

Although the rôles of IL-17 and Thl7 cells in cancer are not fully understood, numerous pro-tumour effects of IL-17 and Thl7 cells are known. For example, Thl7 cells and IL-17 can promote angiogenesis, increase prolifération and survival of tumor cells and activate tumour-promoting transcription factors [35-37],

In certain embodiments, treatment with the compositions of the invention results in a réduction in tumour size or a réduction in tumour growth. In certain embodiments, the compositions of the invention are for use in reducing tumour size or reducing tumour growth. The compositions of the

I3 invention may be effective for reducing tumour size or growth. In certain embodiments, the compositions of the invention are for use in patients with solid tumours. In certain embodiments, the compositions of the invention are for use in reducing or preventing angiogenesîs in the treatment of cancer. IL-17 and Thl7 cells hâve central rôles in angiogenesîs. In certain embodiments, the compositions of the invention are for use in preventing metastasis.

In certain embodiments, the compositions of the invention are for use in treating or preventing breast cancer. The compositions of the invention may be effective for treating breast cancer, and IL-17 and Thl7 cells hâve important rôles in breast cancer [38]. In certain embodiments, the compositions of the invention are for use in reducing tumour size, reducing tumour growth, or reducing angiogenesîs in the treatment of breast cancer. In preferred embodiments the cancer is mammary carcinoma. In preferred embodiments the cancer is stage IV breast cancer.

In certain embodiments, the compositions of the invention are for use in treating or preventing lung cancer. The compositions of the invention may be effective for treating lung cancer, and IL-17 and Thl7 cells hâve important rôles in lung cancer [39], In certain embodiments, the compositions of the invention are for use in reducing tumour size, reducing tumour growth, or reducing angiogenesîs in the treatment of lung cancer. In preferred embodiments the cancer is lung carcinoma.

In certain embodiments, the compositions of the invention are for use in treating or preventing liver cancer. The compositions of the invention may be effective for treating liver cancer, and IL-17 and Thl 7 cells hâve important rôles in liver cancer [40], In certain embodiments, the compositions of the invention are for use in reducing tumour size, reducing tumour growth, or reducing angiogenesîs in the treatment of liver cancer. In preferred embodiments the cancer is hepatoma (hepatocellular carcinoma).

In certain embodiments, the compositions of the invention are for use in treating or preventing carcinoma. The compositions of the invention may be particularly effective for treating carcinoma. In certain embodiments, the compositions of the invention are for use in treating or preventing nonimmunogenic cancer. The compositions of the invention may be effective for treating nonimmunogenic cancers.

In further embodiments, the compositions of the invention are for use in treating or preventing acute lymphoblastic leukemia (ALL), acute myeloid leukemia, adrenocortical carcinoma, basal-cell carcinoma, bile duct cancer, bladder cancer, bone tumor, osteosarcoma/malignant fibrous histiocytoma, brainstem glioma, brain tumor, cerebellar astrocytoma, cérébral astrocytoma/malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumors, breast cancer, bronchial adenomas/carcinoids, Burkitt's lymphoma, carcinoid tumor, cervical cancer, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorders, colon cancer, cutaneous T-cell lymphoma, endométrial cancer, ependymoma, esophageal cancer,

Ewing's sarcoma, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell tumor, glioma, childhood visual pathway and hypothalamic, Hodgkin lymphoma, melanoma, islet cell carcinoma, Kaposi sarcoma, rénal cell cancer, laryngeal cancer, leukaemias, lymphomas, mesothelioma, neuroblastoma, non-Hodgkin lymphoma, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, parathyroid cancer, pharyngeal cancer, pituitary adenoma, plasma cell neoplasia, prostate cancer, rénal cell carcinoma, retinoblastoma, sarcoma, testicular cancer, thyroid cancer, or uterine cancer.

The compositions of the invention may be particularly effective when used in combination with further therapeutic agents. The immune-modulatory effects of the compositions of the invention may be effective when combined with more direct anti-cancer agents. Therefore, in certain embodiments, the invention provides a composition comprising a bacterial strain of the genus Eubacterium and an anticancer agent. In preferred embodiments the anticancer agent is an immune checkpoint inhibitor, a targeted antibody immunotherapy, a CAR-T cell therapy, an oncolytic virus, or a cytostatic drug. In preferred embodiments, the composition comprises an anti-cancer agent selected from the group consisting of: Yervoy (ipilimumab, BMS); Keytruda (pembrolizumab, Merck); Opdivo (nivolumab, BMS); MEDI4736 (AZ/Medlmmune); MPDL3280A (Roche/Genentech); Tremelimumab (AZ/Medlmmune); CT-Oll (pidilizumab, CureTech); BMS-986015 (lirilumab, BMS); MEDI0680 (AZ/Medlmmune); MSB-0010718C (Merck); PF-05082566 (Pfizer); MEDI6469 (AZ/Medlmmune); BMS-986016 (BMS); BMS-663513 (urelumab, BMS); IMP321 (Prima Biomed); LAG525 (Novartis); ARGX-HO (arGEN-X); PF-05082466 (Pfizer); CDX-H27 (varlilumab; CellDex Therapeutics); TRX-518 (GITR Inc,); MK-4166 (Merck); JTX-2011 (Jounce Therapeutics); ARGX115 (arGEN-X); NLG-9189 (indoximod, NewLink Genetics); INCB024360 (Incyte); IPH2201 (Innate Immotherapeutics/AZ); NLG-919 (NewLink Genetics); anti-VISTA (JnJ); Epacadostat (INCB24360, Incyte); F001287 (Flexus/BMS); CP 870893 (University of Pennsylvania); MGA271 (Macrogenîx); Emactuzumab (Roche/Genentech); Galunisertib (Eli Lilly); Ulocuplumab (BMS); BKT140/BL8040 (Biokine Therapeutics); Bavituximab (Peregrine Pharmaceuticals); CC 90002 (Celgene); 852A (Pfizer); VTX-2337 (VentiRx Pharmaceuticals); IMO-2055 (Hybridon, Idera Pharmaceuticals); LY2157299 (Eli Lilly); EW-7197 (Ewha Women's University, Korea); Vemurafenib (Plexxikon); Dabrafenib (Genentech/GSK); BMS-777607 (BMS); BLZ945 (Memorial Sloan-Kettering Cancer Centre); Unituxin (dinutuximab, United Therapeutics Corporation); Blincyto (blinatumomab, Amgen); Cyramza (ramucirumab, Eli Lilly); Gazyva (obinutuzumab, Roche/Biogen); Kadcyla (ado-trastuzumab emtansine, Roche/Genentech); Perjeta (pertuzumab, Roche/Genentech); Adcetris (brentuximab vedotin, Takeda/Millennium); Arzerra (ofatumumab, GSK); Vectibix (panitumumab, Amgen); Avastin (bevacizumab, Roche/Genentech); Erbitux (cetuximab, BMS/Merck); Bexxar (tositumomab-1131, GSK); Zevalin (ibritumomab tiuxetan,

Biogen); Campath (alemtuzumab, Bayer); Mylotarg (gemtuzumab ozogamicin, Pfizer); Herceptin (trastuzumab, Roche/Genentech); Rituxan (rituximab, Genentech/Biogen); volociximab (Abbvie); Enavatuzumab (Abbvie); ABT-414 (Abbvie); Elotuzumab (Abbvie/BMS); ALX-0141 (Ablynx); Ozaralizumab (Ablynx); Actimab-C (Actinium); Actimab-P (Actinium); Milatuzumab-dox (Actinium); Emab-SN-38 (Actinium); Naptumonmab estafenatox (Active Biotech); AFM13 (Affimed); AFMl l (Affimed); AGS-16C3F (Agensys); AGS-16M8F (Agensys); AGS-22ME (Agensys); AGS-15ME (Agensys); GS-67E (Agensys); ALXN6000 (samalizumab, Alexion); ALT836 (Altor Bioscience); ALT-801 (Altor Bioscience); ALT-803 (Altor Bioscience); AMG780 (Amgen); AMG 228 (Amgen); AMG820 (Amgen); AMG172 (Amgen); AMG595 (Amgen); AMGllO (Amgen); AMG232 (adecatumumab, Amgen); AMG2H (Amgen/Medlmmune); BAY20I0112 (Amgen/Bayer); Rilotumumab (Amgen); Denosumab (Amgen); AMP-514 (Amgen); MEDI575 (AZ/Medlmmune); MED13617 (AZ/Medlmmune); MEDI6383 (AZ/Medlmmune); MEDI551 (AZ/Medlmmune); Moxetumomab pasudotox (AZ/Medlmmune); MEDI565 (AZ/Medlmmune); MEDI0639 (AZ/Medlmmune); MEDI0680 (AZ/Medlmmune); MEDI562 (AZ/Medlmmune); AV-380 (AVEO); AV203 (AVEO); AV299 (AVEO); BAY79-4620 (Bayer); Anetumab ravtansine (Bayer); vantictumab (Bayer); BAY94-9343 (Bayer); Sibrotuzumab (Boehringer Ingleheim); BI-836845 (Boehringer Ingleheim); B-701 (BioClin); BIIB015 (Biogen); Obinutuzumab (Biogen/Genentech); BI-505 (Bioinvent); BI-1206 (Bioinvent); TB-403 (Bioinvent); BT-062 (Biotest) BIL-OlOt (Biosceptre); MDX-I203 (BMS); MDX-1204 (BMS); Necitumumab (BMS); CAN-4 (Cantargia AB); CDX-Ol l (Celldex); CDX1401 (Celldex); CDX301 (Celldex); U31565 (Daiichi Sankyo); patritumab (Daiichi Sankyo); tigatuzumab (Daiichî Sankyo); nimotuzumab (Daiichi Sankyo); DS-8895 (Daiichi Sankyo); DS-8873 (Daiichi Sankyo); DS-5573 (Daiichi Sankyo); MQRab-004 (Eisai); MORab-009 (Eisai); MORab-003 (Eisai); MORab-066 (Eisai); LY3012207 (Eli Lilly); LY2875358 (Eli Lilly); LY28I2176 (Eli Lilly); LY3012217(Eli Lilly); LY2495655 (Eli Lilly); LY3012212 (Eli Lilly); LY30122H (Eli Lilly); LY3009806 (Eli Lilly); cixutumumab (Eli Lilly); Flanvotumab (Eli Lilly); IMC-TRl (Eli Lilly); Ramucirumab (Eli Lilly); Tabalumab (Eli Lilly); Zanolimumab (Emergent Biosolution); FG-3019 (FibroGen); FPA008 (Five Prime Therapeutics); FP-1039 (Five Prime Therapeutics); FPA144 (Five Prime Therapeutics); catumaxomab (Fresenius Biotech); 1MAB362 (Ganymed); IMAB027 (Ganymed); HuMax-CD74 (Genmab); HuMax-TFADC (Genmab); GS-5745 (Gilead); GS-6624 (Gilead); OMP-21M18 (demcizumab, GSK); mapatumumab (GSK); IMGN289 (ImmunoGen); IMGN901 (ImmunoGen); IMGN853 (ImmunoGen); IMGN529 (ImmunoGen); IMMU-130 (Immunomedics); milatuzumabdox (Immunomedics); IMMU-H5 (Immunomedics); IMMU-132 (Immunomedics); IMMU-106 (Immunomedics); IMMU-102 (Immunomedics); Epratuzumab (Immunomedics); Clivatuzumab (Immunomedics); IPH41 (Innate Immunotherapeutics); Daratumumab (Janssen/Genmab); CNTO-95 (Intetumumab, Janssen); CNTO-328 (siltuximab, Janssen); KB004 (KaloBios); mogamulizumab (Kyowa Hakko Kirrin); KW-2871 (ecromeximab, Life Science); Sonepcizumab (Lpath);

Margetuximab (Macrogenics); Enoblituzumab (Macrogenics); MGD006 (Macrogenics); MGF007 (Macrogenics); MK-0646 (dalotuzumab, Merck); MK-3475 (Merck); Sym004 (Symphogen/Merck Serono); DH7E6 (Merck Serono); MOR208 (Morphosys); MOR202 (Morphosys); Xmab5574 (Morphosys); BPC-IC (ensituximab, Précision Biologics); TAS266 (Novartis); LFA102 (Novartis); 5 BHQ880 (Novartis/Morphosys); QGE031 (Novartis); HCD122 (lucatumumab, Novartis); LJM716 (Novartis); AT355 (Novartis); OMP-21M18 (Demcizumab, OncoMed); OMP52M51 (Oncomed/GSK); OMP-59R5 (Oncomed/GSK); vantictumab (Oncomed/Bayer); CMC-544 (inotuzumab ozogamicin, Pfizer); PF-03446962 (Pfizer); PF-04856884 (Pfizer); PSMA-ADC (Progenics); REGNI400 (Regeneron); REGN910 (nesvacumab, Regeneron/Sanofi); REGN421 10 (enoticumab, Regeneron/Sanofi); RG7221, RG7356, RG7155, RG7444, RG7116, RG7458, RG7598, RG7599, RG7600, RG7636, RG7450, RG7593, RG7596, DCDS3410A, RG7414 (parsatuzumab), RG7160 (imgatuzumab), RG7159 (obintuzumab), RG7686, RG3638 (onartuzumab), RG7597 (Roche/Genentech); SAR307746 (Sanofi); SAR566658 (Sanofi); SAR650984 (Sanofi); SAR153192 (Sanofi); SAR3419 (Sanofi); SAR256212 (Sanofi), SGN-LIVIA (lintuzumab, Seattle Genetics); 15 SGN-CD33A (Seattle Genetics); SGN-75 (vorsetuzumab mafodotin, Seattle Genetics); SGN-I9A (Seattle Genetics) SGN-CD70A (Seattle Genetics); SEA-CD40 (Seattle Genetics); ibritumomab tiuxetan (Spectrum); MLN0264 (Takeda); ganitumab (Takeda/Amgen); CEP-37250 (Teva); TB-403 (Thrombogenic); VB4-845 (Viventia); Xmab25l2 (Xencor); Xmab5574 (Xencor); nimotuzumab (YM Biosciences); Carlumab (Janssen); NY-ESO TCR (Adaptimmune); MAGE-A-IO TCR 20 (Adaptimmune); CTL019 (Novartis); JCAR015 (Juno Therapeutics); KTE-C19 CAR (Kite Pharma);

UCART19 (Cellectis); BPX-401 (Bellicum Pharmaceuticals); BPX-601 (Bellicum Pharmaceuticals); ATTCK20 (Unum Therapeutics); CAR-NKG2D (Celyad); Onyx-015 (Onyx Pharmaceuticals); HlOl (Shanghai Sunwaybio); DNX-2401 (DNAtrix); VCN-Ol (VCN Biosciences); Colo-Adl (PsiOxus Therapeutics); ProstAtak (Advantagene); Oncos-102 (Oncos Therapeutics); CG0070 (Cold 25 Genesys); Pexa-vac (JX-594, Jennerex Biotherapeutics); GL-ONCl (Genelux); T-VEC (Amgen);

G207 (Medigene); HFIO (Takara Bio); SEPREHVIR (HSV1716, Virttu Biologics); OrienXOlO (OrienGene Biotechnology); Reolysin (Oncolytics Biotech); SVV-OOl (Neotropîx); Cacatak (CVA21, Viralytics); Alimta (Eli Lilly), cisplatin, oxaliplatin, irinotecan, folinic acid, methotrexate, cyclophosphamide, 5-fluorouracil, Zykadia (Novartis), Tafinlar (GSK), Xaikori (Pfizer), Iressa 30 (AZ), Gilotrif (Boehringer Ingelheim), Tarceva (Astellas Pharma), Halaven (Eisai Pharma),

Veliparib (Abbvie), AZD9291 (AZ), Alectinib (Chugai), LDK378 (Novartis), Genetespîb (Synta Pharma), Tergenpumatucel-L (NewLink Genetics), GVlOOl (Kael-GemVax), Tivantinib (ArQule); Cytoxan (BMS); Oncovin (Eli Lilly); Adriamycin (Pfizer); Gemzar (Eli Lilly); Xeloda (Roche); Ixempra (BMS); Abraxane (Celgene); Trelstar (Debiopharm); Taxotere (Sanofi); Nexavar (Bayer); 35 IMMU-132 (Immunomedics); E7449 (Eisai); Thermodox (Celsion); Cometriq (Exellxis); Lonsurf (Taiho Pharmaceuticals); Camptosar (Pfizer); UFT (Taiho Pharmaceuticals); and TS-l (Taiho Pharmaceuticals).

In some embodiments, the one or more Eubacterium bacterial strains is/are the only therapeutically active agent(s) in a composition of the invention. In some embodiments, the bacterial strain(s) in the composition is/are the only therapeutically active agent(s) in a composition of the invention.

Asthma

In preferred embodiments. the compositions of the invention are for use in treating or preventing asthma. The compositions of the invention may achieve a réduction in the recruitment of neutrophils and/or eosinophils into the airways following sensitisation and challenge with house dust mite extract and so they may be useful in the treatment or prévention of asthma. Asthma is a chronic disease characterised by inflammation and restriction of the airways. The inflammation in asthma may be mediated by IL-l7 and/or Thl7 cells, and so the compositions of the invention may be particularly effective for preventing or treating asthma. The inflammation in asthma may be mediated by eosinophils and/or neutrophils.

In certain embodiments, the asthma is éosinophilie or allergie asthma. Eosinophilie and allergie asthma are characterised by increased numbers of eosinophils in peripheral blood and in airway sécrétions and is associated pathologically with thickening of the basement membrane zone and pharmacologically by corticosteroid responsiveness [41]. Compositions that reduce or inhibit eosinophil recruitment or activation may be useful for treating or preventing éosinophilie and allergie asthma.

In additional embodiments, the compositions of the invention are for use in treating or preventing neutrophilie asthma (or non-eosinophilic asthma). High neutrophil numbers are associated with severe asthma that may be insensitive to corticosteroid treatment. Compositions that reduce or inhibit neutrophil recruitment or activation may be useful for treating or preventing neutrophilie asthma.

Eosinophilie and neutrophilie asthma are not mutually exclusive conditions and treatments that help address either the eosinophil and neutrophil responses may be useful for treating asthma in general.

Increased IL-l 7 levels and activation of the Thl7 pathway are associated with severe asthma, so the compositions of the invention may be useful for preventing the development of severe asthma or for treating severe asthma.

In certain embodiments, the compositions of the invention are for use in methods reducing an éosinophilie inflammatory response in the treatment or prévention of asthma, or for use in methods of reducing a neutrophilie inflammatory response in the treatment or prévention of asthma. As noted above, high levels of eosinophils in asthma is associated pathologically with thickening of the basement membrane zone, so reducing éosinophilie inflammatory response in the treatment or prévention of asthma may be able to specifically address this feature of the disease. Also, elevated neutrophils, either in combination with elevated eosinophils or in their absence, is associated with severe asthma and chronic airway narrowing, Therefore, reducing the neutrophilie inflammatory response may be particulariy useful for addressing severe asthma.

In certain embodiments, the compositions reduce peribronchiolar infiltration in allergie asthma, or are for use in reducing peribronchiolar infiltration in the treatment of allergie asthma. In certain embodiments, the compositions reduce peribronchiolar and/or perivascular infiltration in neutrophilie asthma, or are for use in reducing peribronchiolar and/or perivascular infiltration in the treatment of allergie neutrophilie asthma.

In certain embodiments, treatment with compositions of the invention provides a réduction or prevents an élévation in TNFa levels.

In certain embodiments, the compositions of the invention are for use in a method of treating asthma that results in a réduction of the éosinophilie and/or neutrophilie inflammatory response. In certain embodiments, the patient to be treated has, or has previously been identified as having, elevated neutrophil or eosinophil levels, for example as identified through blood sampling or sputum analysis.

The compositions of the invention may be usefiil for preventing the development of asthma in a newbom when administered to the new-bom, or to a prégnant woman. The compositions may be useful for preventing the development of asthma in children. The compositions of the invention may be useful for treating or preventing adult-onset asthma. The compositions of the invention may be useful for managing or alleviating asthma. The compositions of the invention may be particulariy useful for reducing symptoms associated with asthma that is aggravated by allergens, such as house dust mites.

Treatment or prévention of asthma may refer to, for example, an alleviation of the severity of symptoms or a réduction in the frequency of exacerbations or the range of triggers that are a problem for the patient.

Arthritis

In preferred embodiments, the compositions of the invention are for use in treating or preventing rheumatoid arthritis (RA). The compositions ofthe invention may achieve a réduction in the clinical sîgns of RA in a mouse model, reduce cartilage and bone damage, and reduce the IL-17 inflammatory response, and so they may be useful in the treatment or prévention of RA. RA is a systemic inflammatory disorder that primarily affects joints. RA is associated with an inflammatory response that results in swelling of joints, synovial hyperplasia, and destruction of cartilage and bone. IL-17 and Thl7 cells may hâve a key rôle in RA, for example because IL-17 inhibits matrix production in chondrocytes and osteoblasts and activâtes the production and function of matrix metalloproteinases and because RA disease activity is correlated to IL-17 levels and Th-17 cell numbers [42,43], so the compositions of the invention may be particulariy effective for preventing or treating RA.

In certain embodiments, the compositions of the invention are for use in lowering IL-17 levels or preventing élévation of IL-17 levels in the treatment or prévention of RA. In certain embodiments, treatment with compositions of the invention provides a réduction or prevents an élévation in IL-17 levels, in particular IL-17A levels. In certain embodiments, treatment with compositions of the invention provides a réduction or prevents an élévation in IFN-γ or 1L-6 levels.

In certain embodiments, treatment with the compositions of the invention results in a réduction in the swelling of joints. In certain embodiments, the compositions of the invention are for use in patients with swollen joints or patients identified as at risk of having swollen joints. In certain embodiments, the compositions of the invention are for use in a method of reducing joint swelling in RA.

In certain embodiments, treatment with the compositions of the invention results in a réduction in cartilage damage or bone damage. In certain embodiments, the compositions of the invention are for use in reducing or preventing cartilage or bone damage in the treatment of RA. In certain embodiments, the compositions are for use in treating patient with severe RA that are at risk of cartilage or bone damage.

Increased IL-17 levels and Th 17 cell numbers are associated with cartilage and bone destruction in RA [42,43]. IL-17 is known to activate matrix destruction in cartilage and bone tissue and IL-17 has an inhibîtory effect on matrix production în chondrocytes and osteoblasts. Therefore, in certain embodiments, the compositions of the invention are for use in preventing bone érosion or cartilage damage in the treatment of RA. In certain embodiments, the compositions are for use in treating patients that exhibit bone érosion or cartilage damage or patients identified as at risk of bone érosion or cartilage damage.

TNF-α is also associated with RA, but TNF-α is not involved in the pathogenesis of the later stages of the disease. In contrast, IL-17 has a rôle throughout ail stages of chronic disease [44]. Therefore, in certain embodiments the compositions of the invention are for use in treating chronic RA or latestage RA, such as disease that includes joint destruction and loss of cartilage. In certain embodiments, the compositions of the invention are for treating patients that hâve previously received anti-TNF-α therapy. In certain embodiments, the patients to be treated do not respond or no longer respond to anti-TNF-α therapy.

The compositions of the invention may be useful for modulating a patient’s immune system, so in certain embodiments the compositions of the invention are for use in preventing RA in a patient that has been identified as at risk of RA, or that has been diagnosed with early-stage RA. The compositions of the invention may be useful for preventing the development of RA.

The compositions of the invention may be useful for managing or allevîating RA. The compositions of the invention may be particularly useful for reducing symptoms associated with joint swelling or bone destruction. Treatment or prévention of RA may refer to, for example, an alleviation of the severity of symptoms or a réduction in the frequency of exacerbations or the range of triggers that are a problem for the patient.

Multiple sclerosis ïn preferred embodiments, the compositions of the invention are for use in treating or preventing multiple sclerosis. The compositions of the invention may achieve a réduction in the disease incidence and disease severity in a mouse model of multiple sclerosis (the EAE model), and so they may be useful in the treatment or prévention of multiple sclerosis. Multiple sclerosis is an inflammatory disorder associated with damage to the myelin sheaths of neurons, pailicularly in the brain and spinal column. Multiple sclerosis is a chronic disease, which is progressively incapacitating and which evolves in épisodes. IL-17 and Thl7 cells may hâve a key rôle in multiple sclerosis, for example because IL-17 levels may correlate with multiple sclerosis lésions, IL-17 can disrupt blood brain barrier endothélial cell tight junctions, and Thl7 cells can mîgrate into the central nervous system and cause neuronal loss [45,46]. Therefore, the compositions of the invention may be particularly effective for preventing or treating multiple sclerosis.

In certain embodiments, treatment with the compositions of the invention results in a réduction in disease incidence or disease severity. In certain embodiments, the compositions of the invention are for use in reducing disease incidence or disease severity. In certain embodiments, treatment with the compositions of the invention prevents a décliné in motor function or results in improved motor function. In certain embodiments, the compositions of the invention are for use in preventing a décliné in motor function or for use in improving motor function. In certain embodiments, treatment with the compositions of the invention prevents the development of paralysis. In certain embodiments, the compositions of the invention are for use în preventing paralysis in the treatment of multiple sclerosis.

The compositions of the invention may be useful fbr modulating a patient’s immune system, so in certain embodiments the compositions of the invention are for use in preventing multiple sclerosis in a patient that has been identified as at risk of multiple sclerosis, or that has been diagnosed with early-stage multiple sclerosis or “relapsing-remitting” multiple sclerosis. The compositions of the invention may be useful for preventing the development of sclerosis.

The compositions of the invention may be useful for managing or alleviating multiple sclerosis. The compositions of the invention may be particularly useful for reducing symptoms associated with multiple sclerosis. Treatment or prévention of multiple sclerosis may refer to, for example, an alleviation of the severity of symptoms or a réduction in the frequency of exacerbations or the range of triggers that are a problem for the patient.

Modes of administration

Preferably, the compositions of the invention are to be administered to the gastrointestinal tract in order to enable delivery to and / or partial or total colonisation of the intestine with the bacterial strain of the invention. Generally, the compositions of the invention are administered orally, but they may be administered rectally, intranasally, or via buccal or sublingual routes.

In certain embodiments, the compositions of the invention may be administered as a foam, as a spray or a gel.

In certain embodiments, the compositions of the invention may be administered as a suppository, such as a rectal suppository, for example in the form of a theobroma oil (cocoa butter), synthetic hard fat (e.g. suppocire, witepsol), glycero-gelatin, polyethylene glycol, or soap glycerin composition.

In certain embodiments, the composition of the invention is administered to the gastrointestinal tract via a tube, such as a nasogastric tube, orogastric tube, gastric tube, jejunostomy tube (J tube), percutaneous endoscopie gastrostomy (PEG), or a port, such as a chest wall port that provides access to the stomach, jéjunum and other suitable access ports.

The compositions of the invention may be administered once, or they may be administered sequentially as part of a treatment regimen. In certain embodiments, the compositions of the invention are to be administered daily.

In certain embodiments of the invention, treatment according to the invention is accompanied by assessment of the patient’s gut microbiota. Treatment may be repeated if delivery of and / or partial or total colonisation with the strain of the invention is not achieved such that efficacy is not observed, or treatment may be ceased if delivery and / or partial or total colonisation is successful and efficacy is observed.

In certain embodiments, the composition of the invention may be administered to a prégnant animal, for example a mammal such as a human in order to prevent an inflammatory or autoimmune disease developing in her child in utero and / or after it îs bom.

The compositions of the invention may be administered to a patient that has been diagnosed with a disease or condition mediated by IL·-17 or the Thl7 pathway, or that has been identified as being at risk of a disease or condition mediated by IL-l 7 or the Thl7 pathway. The compositions may also be administered as a prophylactic measure to prevent the development of diseases or conditions mediated by IL-17 or the Thl 7 pathway in a healthy patient.

The compositions of the invention may be administered to a patient that has been identified as having an abnormal gut microbiota. For example, the patient may hâve reduced or absent colonisation by Eubacterium.

The compositions of the invention may be administered as a food product, such as a nutritional supplément.

Generally, the compositions of the invention are for the treatment of humans, although they may be used to treat animais including monogastric mammals such as poultry, pigs, cats, dogs, horses or rabbits. The compositions of the invention may be useful for enhancing the growth and performance of animais. If administered to animais, oral gavage may be used.

Compositions

Generally, the composition of the invention comprises bacteria. In preferred embodiments of the invention, the composition is formulated in freeze-dried form. For example, the composition of the invention may comprise granules or gelatin capsules, for example hard gelatin capsules, comprising a bacterial strain of the invention.

Preferably, the composition of the invention comprises lyophilised bacteria. Lyophilisation of bacteria is a well-established procedure and relevant guidance is available in, for example, references [47-49].

Alternatively, the composition of the invention may comprise a live, active bacterial culture.

In some embodiments, the bacterial strain in the composition of the invention has not been înactivated, for example, has not been heat-înactîvated. In some embodiments, the bacterial strain in the composition of the invention has not been killed, for example, has not been heat-killed. In some embodiments, the bacterial strain in the composition of the invention has not been attenuated, for example, has not been heat-attenuated. For example, in some embodiments, the bacterial strain in the composition of the invention has not been killed, înactivated and/or attenuated. For example, in some embodiments, the bacterial strain in the composition of the invention is live. For example, in some embodiments, the bacterial strain in the composition of the invention is viable. For example, in some embodiments, the bacterial strain in the composition of the invention is capable of partially or totally colonising the intestine. For example, in some embodiments, the bacterial strain in the composition of the invention is viable and capable of partially or totally colonising the intestine.

In some embodiments, the composition comprises a mixture of live bacterial strains and bacterial strains that hâve been killed.

In preferred embodiments, the composition of the invention is encapsulated to enable delivery of the bacterial strain to the intestine. Encapsulation protects the composition from dégradation until delivery at the target location through, for example, rupturing with Chemical or physical stimuli such as pressure, enzymatic activity, or physical disintegration, which may be triggered by changes in pH. Any appropriate encapsulation method may be used. Exemplary encapsulation techniques include entrapment within a porous matrix, attachment or adsorption on solid carrier surfaces, self18795 aggregation by flocculation or with cross-linking agents, and mechanical containment behind a microporous membrane or a microcapsule. Guidance on encapsulation that may be useful for preparing compositions of the invention is available in, for example, référencés [50] and [51].

The composition may be administered orally and may be in the form of a tablet, capsule or powder. Encapsulated products are preferred because Eubacterium contortuin are anaerobes. Other ingrédients (such as vitamin C, for example), may be included as oxygen scavengers and prebiotic substrates to improve the delivery and / or partial or total colonisation and survival in vivo. Alternatively, the probiotic composition of the invention may be administered orally as a food or nutritional product, such as milk or whey based fermented dairy product, or as a pharmaceutical product.

The composition may be formulated as a probiotic.

A composition of the invention includes a therapeutically effective amount of a bacterial strain ofthe invention. A therapeutically effective amount of a bacterial strain is sufficient to exert a bénéficiai effect upon a patient. A therapeutically effective amount of a bacterial strain may be sufficient to resuit in delivery to and / or partial or total colonisation of the patient’s intestine.

A suitable daily dose of the bacteria, for example for an adult human, may be from about l x KF to about l x Ιθ” colony forming units (CFU); for example, from about l x 10⁷ to about l x l0^l° CFU; in another example from about l x 10⁶ to about l x 10^l° CFU.

In certain embodiments, the composition contains the bacterial strain in an amount of from about l x 10⁶ to about l x Ιθ CFU/g, respect to the weight of the composition; for example, from about I x 10⁸ to about I x I O¹⁰ CFU/g. The dose may be, for example, 1 g, 3g. 5g, and 10g.

Typically, a probiotic, such as the composition of the invention, is optionally combined with at least one suitable prebiotic compound. A prebiotic compound is usually a non-digestible carbohydrate such as an oligo- or polysaccharide, or a sugar alcohol, which is not degraded or absorbed in the upper digestive tract. Known prebiotics include commercial products such as inulin and transgalactoolîgosaccharides.

In certain embodiments, the probiotic composition of the présent invention includes a prebiotic compound in an amount of from about 1 to about 30% by weight, respect to the total weight composition, (e.g. from 5 to 20% by weight). Carbohydrates may be selected from the group consisting of: fructo- oligosaccharides (or FOS), short-chaîn fructo-oligosaccharides, inulin, isomaltoligosaccharides, pectins, xylo-oligosaccharides (or XOS), chitosan-oligosaccharides (or COS), betaglucans, arable gum modified and résistant starches, polydextrose, D-tagatose, acacia fibers, carob, oats, and citrus fibers. In one aspect, the prebiotics are the short-chain fructo-oligosaccharides (for simplicity shown herein below as FOSs-c.c); said FOSs-c.c. are not digestible carbohydrates.

generally obtained by the conversion of the beet sugar and including a saccharose molécule to which three glucose molécules are bonded.

The compositions of the invention may comprise pharmaceutically acceptable excipients or carriers. Examples of such suitable excipients may be found in the reference [52]. Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art and are described, for example, in reference [53], Examples of suitable carriers include lactose, starch, glucose, methyl cellulose, magnésium stéarate, mannitol, sorbitol and the like. Examples of suitable diluents include éthanol, glycerol and water. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient or diluent any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s). Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, freeflow lactose, beta-lactose, corn sweeteners, natural and synthetic gums, such as acacia, tragacanlh or sodium alginate, carboxymethyl cellulose and polyethylene glycoL Examples of suitable lubricants include sodium oleate, sodium stéarate, magnésium stéarate, sodium benzoate, sodium acetate, sodium chloride and the like. P réservât ives, stabilizers, dyes and even flavouring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used.

The compositions of the invention may be formulated as a food product. For example, a food product may provide nutritional benefit in addition to the therapeutic effect of the invention, such as in a nutritional supplément. Similarly, a food product may be formulated to enhance the taste of the composition of the invention or to make the composition more attractive to consume by being more similar to a common food item, rather than to a pharmaceutical composition. In certain embodiments, the composition of the invention is formulated as a milk-based product. The term milk-based product means any liquid or semi-solid milk- or whey- based product having a varying fat content. The milk-based product can be, e.g., cow's milk, goat's milk, sheep's mîlk, skimmed milk, whole milk, milk recombined from powdered milk and whey without any processing, or a processed product, such as yoghurt, curdled milk, curd, sour milk, sour whole milk, butter milk and other sour milk products. Another important group includes milk beverages, such as whey beverages, fermented milks, condensed milks, infant or baby milks; flavoured milks, ice cream; milk-containing food such as sweets.

In some embodiments, the compositions of the invention comprise one or more bacterial strains of the genus Eubacterium and do not contain bacteria from any other genus, or which comprise only de mifümis or biologically irrelevant amounts of bacteria from another genus. Thus, in some embodiments, the invention provides a composition comprising one or more bacterial strains of the genus Eubacterium, which does not contain bacteria from any other genus or which comprises only de mininiis or biologically irrelevant amounts of bacteria from another genus, for use in therapy.

In certain embodiments, the compositions of the invention contain a single bacterial strain or species and do not contain any other bacterial strains or species. Such compositions may comprise only de mininiis or biologically irrelevant amounts of other bacterial strains or species. Such compositions may be a culture that is substantially free from other species of organism. Thus, in some embodiments, the invention provides a composition comprising a single bacterial strain or species of the genus Eubacterium, which does not contain bacteria from any other genus or which comprises only de mininiis or biologically irrelevant amounts of bacteria from another genus for use in therapy.

In some embodiments, the compositions of the invention comprise more than one bacterial strain or species. For example, in some embodiments, the compositions of the invention comprise more than one strain from within the same species (e.g. more than l, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 or 45 strains), and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions of the invention comprise less than 50 strains from within the same species (e.g. less than 45, 40, 35, 30, 25, 20, 15, 12, 10, 9, 8, 7, 6, 5, 4 or 3 strains), and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions of the invention comprise l-40, l-30, l-20, l-I9, 1-18, I-15, 1-10, l-9, l-8, I-7, l-6, l-5, l-4, l-3, l-2, 250, 2-40, 2-30, 2-20, 2-15, 2-10, 2-5, 6-30, 6-15, 16-25, or 31-50 strains from within the same species and, optionally, do not contain bacteria from any other species. In some embodiments, the compositions of the invention comprise more than one species from within the same genus (e.g. more than l, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 15, 17, 20, 23, 25, 30, 35 or 40 species), and, optionally, do not contain bacteria from any other genus. In some embodiments, the compositions of the invention comprise less than 50 species from within the same genus (e.g. less than 50, 45, 40, 35, 30, 25, 20, 15, 12, 10, 8, 7, 6, 5, 4 or 3 species), and. optionally, do not contain bacteria from any other genus. In some embodiments, the compositions of the invention comprise l-50, l-40, l-30, l-20, 1-15, 1-10, l -9, l -8, l -7, I -6, l -5, l -4, l -3, l -2, 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 2-5, 6-30, 6-15, 16-25, or 31 50 species from within the same genus and, optionally. do not contain bacteria from any other genus. The invention comprises any combination of the foregoing.

In some embodiments, the composition comprises a microbial consortium. For example, in some embodiments, the composition comprises the Eubacterium bacterial strain as part of a microbial consortium. For example, in some embodiments, the Eubacterium bacterial strain is présent in combination with one or more (e.g. at least 2, 3, 4, 5, 10, 15 or 20) other bacterial strains from other généra with which it can live symbiotically in vivo in the intestine. For example, in some embodiments, the composition comprises a bacterial strain of Eubacterium contortum in combination with a bacterial strain from a different genus. In some embodiments, the microbial consortium comprises two or more bacterial strains obtained from a faeces sample of a single organism, e.g. a human. In some embodiments, the microbial consortium is not found together in nature. For example, in some embodiments, the microbial consortium comprises bacterial strains obtained from faeces samples of at least two different organisais. In some embodiments, the two different organisais are from the same species, e.g. two different humans. In some embodiments, the two different organisais are an infant human and an adult human. In sonie embodiments, the two different organisms are two different adult humans. In some embodiments, the two different organisins are a human and a non-human mammal.

In some embodiments, the composition of the invention additionally comprises a bacterial strain that has the same safety and therapeutic efficacy characteristics as strain MRX050 deposited as NCIMB 42689, but which is not MRX050 deposited as NCIMB 42689, or which is not a Eubacterium contortum, or which is not a Eubacterium.

In some embodiments in which the composition ofthe invention comprises more than one bacterial strain, species or généra, the individual bacterial strains, species or généra may be for separate, siniultaneous or sequential administration. For example, the composition may comprise ail of the more than one bacterial strain, species or généra, or the bacterial strains, species or généra may be stored separately and be administered separately, simultaneously or sequentially. In some embodiments, the more than one bacterial strains, species or généra are stored separately but are mixed together prior to use.

In some embodiments, the bacterial strain for use in the invention is obtained from human adult faeces. In some embodiments in which the composition of the invention comprises more than one bacterial strain, ail of the bacterial strains are obtained from human adult faeces or if other bacterial strains are present they are present only in de minîmis amounts. The bacteria may hâve been cultured subséquent to being obtained from the human adult faeces and being used in a composition of the invention.

As mentioned above, in some embodiments, the bacterial strain of the invention is the only therapeutically active agent in a composition of the invention. In some embodiments, the bacterial strain(s) in the composition is/are the only therapeutically active agent(s) in a composition of the invention.

The compositions for use in accordance with the invention may or may not require marketing approval.

In certain embodiments, the invention provides the above pharmaceutical composition, wherein said bacterial strain is lyophilised. In certain embodiments, the invention provides the above pharmaceutical composition, wherein said bacterial strain is spray dried. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is live. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is viable. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is capable of partially or totally colonising the intestine. In certain embodiments, the invention provides the above pharmaceutical composition, wherein the bacterial strain is lyophilised or spray dried and wherein it is viable and capable of partially or totally colonising the intestine.

In some cases, the lyophilised or spray dried bacterial strain is reconstituted prior to administration. In some cases, the reconstitution is by use of a diluent described herein.

The compositions of the invention can comprise pharmaceutically acceptable excipients, diluents or carriers.

In certain embodiments, the invention provides a pharmaceutical composition comprising: a bacterial strain as used in the invention; and a pharmaceutically acceptable excipient, carrier or diluent; wherein the bacterial strain is in an amount sufficient to treat a disorder when administered to a subject in need thereof; and wherein the disorder is selected from the group consisting of uveitis; cancer, such as breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer; multiple sclerosis; arthritis, such as rheumatoid arthritis, osteoarthrîtîs, psoriatic arthritis, or juvénile îdiopathic arthritis; neuromyelitis optica (Devic's disease); ankylosing spondylitis; spondyloarthritis; psoriasis; systemic lupus erythematosus; inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; celiac disease; asthma, such as allergie asthma or neutrophilie asthma; chronic obstructive pulmonary disease (COPD); scleritis; vasculitis; Behcet’s disease; atherosclerosis; atopie dermatitis; emphysema; periodontitis; allergie rhinitis; and allograft rejection.

In certain embodiments, the invention provides pharmaceutical composition comprising: a bacterial strain as used in the invention; and a pharmaceutically acceptable excipient, carrier or diluent; wherein the bacterial strain is in an amount sufficient to treat or prevent a disease or condition mediated by IL-I7 or the Thl7 pathway. In preferred embodiments, said disease or condition is selected from the group consisting of uveitis; cancer, such as breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer; multiple sclerosis; arthritis, such as rheumatoid arthritis, osteoarthrîtîs, psoriatic arthritis, or juvénile îdiopathic arthritis; neuromyelitis optica (Devic’s disease); ankylosing spondylitis; spondyloarthritis; psoriasis; systemic lupus erythematosus; inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis; celiac disease; asthma, such as allergie asthma or neutrophilie asthma; chronic obstructive pulmonary disease (COPD);

scleritis; vasculitis; Behcet's disease; atherosclerosis; atopie dermatitis; emphysema; periodontitis; allergie rhinitis; and allograft rejection..

In certain embodiments, the invention provides the above pharmaceutical composition, wherein the amount of the bacteriai strain is from about l * 10³ to about l ^x 10¹¹ colony forming units per gram with respect to a weight of the composition.

In certain embodiments, the invention provides the above pharmaceutical composition, wherein the composition is administered at a dose of 1 g, 3 g, 5 g or 10 g.

In certain embodiments, the invention provides the above pharmaceutical composition, wherein the composition is administered by a method selected from the group consisting of oral, rectal, subeutaneous, nasal, buccal, and sublingual.

In certain embodiments, the invention provides the above pharmaceutical composition, comprising a carrier selected from the group consisting of lactose, starch, glucose, methyl cellulose, magnésium stéarate, mannitol and sorbitol.

In certain embodiments, the invention provides the above pharmaceutical composition, comprising a diluent selected from the group consisting of éthanol, glycerol and water.

In certain embodiments, the invention provides the above pharmaceutical composition, comprising an excipient selected from the group consisting of starch, gelatin, glucose, anhydrous lactose, freeflow lactose, bcta-lactosc, corn sweetener, acacia, tragacanth, sodium alginate, carboxymethyl cellulose, polyethylene glycol, sodium oleate, sodium stéarate, magnésium stéarate, sodium benzoate, sodium acetate and sodium chloride.

In certain embodiments, the invention provides the above pharmaceutical composition, further comprising at least one of a preservative, an antioxidant and a stabilizer.

In certain embodiments, the invention provides the above pharmaceutical composition, comprising a preservative selected from the group consisting of sodium benzoate, sorbîc acid and esters of phydroxybenzoic acid.

In certain embodiments, the invention provides the above pharmaceutical composition, wherein when the composition is stored in a sealed container at about 4°C or about 25°C and the container is placed in an atmosphère having 50% relative humidity, at least 80% of the bacteriai strain as measured in colony forming units, remains after a period of at least about: 1 month. 3 months, 6 months, 1 year, 1.5 years, 2 years, 2.5 years or 3 years.

In some embodiments, the composition of the invention is provided in a sealed container comprising a composition as described herein. In some embodiments, the sealed container is a sachet or bottle.

In some embodiments, the composition of the invention is provided in a syringe comprising a composition as described herein.

The composition of the présent invention may, in some embodiments, be provided as a pharmaceutical formulation. For example, the composition may be provided as a tablet or capsule. In some embodiments, the capsule is a gélatine capsule (“gel-cap”).

In some embodiments, the compositions of the invention are administered orally. Oral administration may involve swallowing, so that the compound enters the gastrointestinal tract, and/or buccal, lingual, or sublingual administration by which the compound enters the blood stream directly from the mouth.

Pharmaceutical formulations suitable for oral administration include solid plugs, solid microparticulates, semi-solid and liquid (including multiple phases or dispersed Systems) such as tablets; soft or hard capsules containing multi- or nano-particulates, liquids (e.g. aqueous solutions), émulsions or powders; lozenges (including liquid-filled); chews; gels; fast dispersing dosage forms; films; ovules; sprays; and buccal/mucoadhesive patches.

In some embodiments the pharmaceutical formulation is an enteric formulation, i.e. a gastro-résistant formulation (for example, résistant to gastric pH) that is suitable for delivery of the composition of the invention to the intestine by oral administration. Enteric formulations may be particularly useful when the bacteria or another component of the composition is acid-sensitive, e.g. prone to dégradation under gastric conditions.

In some embodiments, the enteric formulation comprises an enteric coating. In some embodiments, the formulation is an enteric-coated dosage form. For example, the formulation may be an entericcoated tablet or an enteric-coated capsule, or the like. The enteric coating may be a conventional enteric coating, for example, a conventional coating for a tablet, capsule, or the like for oral delivery. The formulation may comprise a film coating, for example, a thin film layer of an enteric polymer, e.g. an acid-insoluble polymer.

In some embodiments, the enteric formulation is intrinsically enteric, for example, gastro-résistant without the need for an enteric coating. Thus, in some embodiments, the formulation is an enteric formulation that does not comprise an enteric coating. In some embodiments, the formulation is a capsule made from a thermogelling material. In some embodiments, the thermogelling material is a cellulosic material, such as methylcellulose, hydroxymethylcellulose or hydroxypropylmethylcellulose (HPMC). In some embodiments, the capsule comprises a shell that does not contain any film forming polymer. In some embodiments, the capsule comprises a shell and the shell comprises hydroxypropylmethylcellulose and does not comprise any film forming polymer (e.g. see [54 ]). In some embodiments, the formulation is an intrinsically enteric capsule (for example, Vcaps® from Capsugel).

In some embodiments, the formulation is a soft capsule. Soft capsules are capsules which may, owing to additions of softeners, such as, for example, glycerol, sorbitol, maltitol and polyethylene glycols, present in the capsule shell, hâve a certain elasticity and softness. Soft capsules can be produced, for example, on the basis of gélatine or starch. Gelatine-based soft capsules are commercially available from various suppliers. Depending on the method of administration, such as, for example, orally or rectally, soft capsules can hâve various shapes, they can be, for example, round, oval, oblong or torpedo-shaped. Soft capsules can be produced by conventîonal processes, such as, for example, by the Scherer process, the Accogel process or the droplet or blowing process.

Culturing methods

The bacterial strains for use in the present invention can be cultured using standard microbiology techniques as detailed in, for example, references [55-57].

The solid or liquid medium used for culture may be YCFA agar or YCFA medium. YCFA medium may include (per 100ml, approximate values): Casitone (l.O g), yeast extract (0.25 g), NaHCOj (0.4 g), cysteine (0.1 g), K₂HPO₄ (0.045 g), KH₂PO₄ (0.045 g), NaCI (0.09 g), (NH₄)₂SO₄ (0.09 g), MgSO₄ 7H₂O (0.009 g), CaCl₂ (0.009 g), resazurin (0.I mg), hemin (I mg), biotin (l pg), cobalamin (l pg)./?-aminobenzoic acid (3 pg), folie acid (5 pg), and pyridoxamine (15 pg).

Bacterial strains for use in vaccine compositions

The inventors hâve identified that the bacterial strains of the invention are useful for treating or preventing diseases or conditions mediated by IL-17 or the Thl 7 pathway. This is likely to be a resuit of the effect that the bacterial strains of the invention hâve on the host immune system. Therefore, the compositions of the invention may also be useful for preventing diseases or conditions mediated by IL-17 or the Thl 7 pathway, when administered as vaccine compositions. In certain such embodiments, the bacterial strains of the invention are viable. In certain such embodiments, the bacterial strains of the invention are capable of partially or totally colonising the intestine. In certain such embodiments, the bacterial strains of the invention are viable and capable of partially or totally colonising the intestine. In other certain such embodiments, the bacterial strains of the invention may be killed, inactivated or attenuated. In certain such embodiments, the compositions may comprise a vaccine adjuvant. In certain embodiments, the compositions are for administration via injection, such as via subeutaneous injection.

General

The practice of the present invention will employ, unless otherwise indicated, conventîonal methods of chemistry, biochemistry, molecular biology, immunology and pharmacology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g,, references [58] and [59-65], etc.

The term “comprising” encompasses “including” as well as “consisting” e.g. a composition “comprising” X may consist exclusively of X or may include something additional e.g. X + Y.

The term “about” in relation to a numerical value x is optional and means, for example, x+10%.

The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omîtted from the définition of the invention.

References to a percentage sequence identity between two nucléotide sequences means that, when aligned, that percentage of nucléotides are the same in comparing the two sequences. This alignment and the percent homology or sequence identity can be determined using software programs known in the art, for example those described in section 7.7.18 of ref. [66]. A preferred alignment is determined by the Smith-Waterman homology search algorithm using an affine gap search with a gap open penalty of 12 and a gap extension penalty of 2, BLOSUM matrix of 62. The SmithWaterman homology search algorithm is disclosed in ref. [67].

Unless specifically stated, a process or method comprising numerous steps may comprise additional steps at the beginning or end of the method, or may comprise additional intervening steps. Also, steps may be combined, omitted or performed in an alternative order, if appropriate.

Various embodiments of the invention are described herein. It will be appreciated that the features specified in each embodiment may be combined with other specified features, to provide further embodiments. In particular, embodiments highlighted herein as being suitable, typical or preferred may be combined with each other (except when they are mutually exclusive).

MODES FOR CARRYING OUT THE INVENTION

Example 1 — Efficacy of bacterial inocula in a mouse model of uveitis

Summarv

This study used a mouse model of interphotoreceptor retinoid-binding protein (IRBP)-induced uveitis to test the effects of bacterial administration on uveitis. Uveitis is a sight-threatening condition resulting from intraocular inflammation and retinal tissue destruction. This disease can be studied in rodents in a model of experimental autoimmune uveoretinitis (EAU) [68]. EAU is an organ-specific disorder where Thl/Thl7 cells are directed toward retinal antigens and produce cytokines that activate résident and infiltrating mononuclear cells ieading to tissue destruction. EAU can be induced in mice by challenge with retinal antigens including interphotoreceptor retinoid binding protein peptide (IRBPp). Disease onset normally occurs from day 8-9 and peaks after days 14-15. Sîgns of clinical disease can be monitored using topical endoscopie fondai imaging (TEFI).

Strain

MRXO50: Eubacterium contortum.

The strain used in this example has been deposited as NCIMB 42689.

Biotherapeutic was provided in glycerol stock. Mîcrobiological growth media (YCFA) was used for the culture of the agent.

Mice

The mîce were strain C57BL/6 and were over 6 weeks old at the beginning of the study. 72 mice were used (+ 36 Satellite animais). Unhealthy animais were excluded from the study. Animais were housed in spécifie pathogen free (spf) conditions, in a thermostatically monitored holding room (22 ± 4°C). Animais were allowed to acclimatise under standard animal house conditions for a minimum of one week prior to use. The health status of the animais was monitored throughout this period and the suitability of each animal for experimental use was assessed prior to study start, Mice were housed in groups of up to 10 animais per cage for the duration of the study. Irradiated pellet diet (Lab diet, EU Rodent diet 22%, 5LF5) and water were available ad libitum throughout the acclimatisation and study periods. It is unlikely that any constituent of the diet or water interfered with the study.

Experimental Ondine

Adult female C57BL/6 mice were randomly aliocated to experimental groups and allowed to acclimatise for one week. Treatments were administered according to the schedule below. On Day 0, animais were administered with an émulsion containing 200 pg of interphotoreceptor retinoid binding protein peptide l-20 (IRBP p l -20) in complété Freund’s adjuvant (CFA) supplemented with

2.5 mg/ml Mycobacterium Tttberculosis H37 Ra by subeutaneous injection. Also on Day 0, animais were administered with l .5 pg Bordetella Pertussis toxin by intra-peritoneal injection. From Day 14, animais are weîghed three times per week. From Day -l until the end of the experiment on Day 42, animais are monitored twice per week for clinical signs of uveitis using topical endoscopie fondai imaging (TEFI).

Administration schedule

AH Groups are n= l2

Vehicle for oral administration is YCFA medium.

Administration volume for twice daily oral administration is 5 ml/kg.

Group	Treatment	Dose	Route	Frequency	Disease Induction
1	Vehicle	5 ml/kg	PO	BID Day -14-End	Day 0: IRBP/CFA, SC Day 0: PTx. IP
2	MRX050	5 ml/kg

PO: oral administration, BID: twice daily, SC: subcutaneous injection, IP: intra-peritoneal injection, IRBP: interphotoreceptor binding protein, CFA: complété Freund’s adjuvant, PTx:

Pertussis toxin

A positive control group was also tested using treatment with the drug cyclosporin A.

Readouts

Bodyweights. From Day -14, animais are weighed three times a week. Animais with a bodyweight loss equal to or greater than 15% of their initial (Day 0) bodyweight on two consecutive occasions are culled.

Non-specific clinical observations. From Day -14 until the end of the experiment, animais are 10 checked daily for non-specific clinical signs to include abnormal posture (hunched), abnormal coat condition (piloerection) and abnormal activity levels (reduced or increased activity).

Clinical Scores: Retinal iniaging by topical endoscopie fundal imaging (TEFI). From Day -l until the end of the experiment, animais are scored twice per week for clinical signs of uveitis. Retinal images are captured using TEFI in non-anaesthetised but restrained animais following pupil 15 dilatation using Tropicamide I% then Phenylephrine hydrochloride 2.5%. Retinal images are scores using the following System. The maximum cumulative score is 20.

Score	Optic dise Inflammation	Retinal vessels	Retinal tissue Infiltration	Structural damage
1	Minimal	1-4 mild euffings	1-4 small lésions or 1 linear lésion	Retinal lésions or atrophy involving !4 to % of retinal area
2	Mild	>4 mild euffings or 1 -3 moderate euffings	5-10 small lésions or 2-3 linear lésions	Panretinal atrophy with multiple small lésions (scars) or <3 linear lésions (scars)
3	Moderate	>3 moderate euffings	>10 small lésions or >3 linear lésions	Panretinal atrophy with >3 linear lésions or confluent lésions (scars)
4	Severe	>1 severe euffings	Linear lésion confluent	Retinal detachment with folding

5	Not visible (white-out or severe detachment)

Results

The results of the study are shown in Figures 1 and 2.

Clinical Scores: Retinal imaging by topical endoscopie fundal imaging (TEFI). TEFI scores data measured in the Control group from Day 0 until Day 28 were analysed by Kruskal-Wallis test for non-parametric data followed by Dunn’s post-test for multiple comparisons between experimental days.

IRBP administration induced a significant increase in the TEFI scores measured from Day 14 (p < 0.01) and on Day 28 (p < 0.0001 ) when compared to Day 0 in the Control group (Figure I ).

TEFI scores measured in the experimental groups on Day 28 were analysed using a one-way ANOVA. As expected, a significant decrease in the scores was observed in the positive control cyclosporine A group. There was also a statistically significant decrease in the scores for the MRX050-treated group (p<0.001), relative to the négative control (Figure 2).

Conclusions. Clinical scores determined by TEFI increased from Day 14, as expected in this model of IRJBP-induced uveitis. By Day 28, a striking and statistically significant réduction in disease incidence and disease severity was observed in the MRX050-treated group, which was comparable to that seen for the positive control group. In particular, these data indicate that treatment with the strain MRX050 reduced retinal damage, optic dise inflammation and/or retinal tissue infiltration by inflammatory cells (see TEFI retinal image scoring system above). These data indicate the strain MRX050 may be useful for treating or preventing uveitis.

Example 2 - Stability testing

A composition described herein containing at least one bacterial strain described herein is stored in a sealed container at 25 C or 4 C and the container is placed in an atmosphère having 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90% or 95% relative humidity. After 1 month, 2 months, 3 months, 6 months, 1 year, 1.5 years, 2 years, 2.5 years or 3 years, at least 50%, 60%, 70%, 80% or 90% of the bacterial strain shall remain as measured in colony forming units determined by standard protocols.

Sequences

SEQ ID NO:1 (Eubacterium contortum partial 16S rRNA gene, type strain DSM 3982T, clone 1 FR749945) gateetgget caggatgaac gctggcggcg tgcttaacac atgcaagtcg agcgaagcgc tttaettaga tttcttcgga ttgaagagtt ttgcgactga gcggcggacg ggtgagtaac

121 gcgtgggtaa cctgcctcat acagggggat aacagttaga aatgaetget aataccgcat

181	aagaccacgg	taccgcatgg	tacagtggga	aaaactccgg	tggtatgaga	tggacccgcg
241	tctgattagc	tagttggtaa	ggtaacggct	taccaaggcg	acgatcagta	gccgacctga
301	gagggtgacc	ggccacattg	ggactgagac	acggcccaaa	ctcctacggg	aggcagcagt
361	ggggaatatt	gcacaatggg	ggaaaccctg	atgcagcgac	gccgcgtgaa	ggatgaagta
421	tttcggtatg	taaacttcta	tcagcaggga	agaaaatgac	ggtacctgac	taagaagccc
481	cggctaacta	cgtgccagca	gccgcggtaa	tacgtagggg	gcaagcgtta	tccggattta
541	ctgggtgtaa	agggagcgta	gacggttatg	taagtctgat	gtgaaaaccc	ggggctcaac
601	cccgggactg	cattggaaac	tatgtaacta	gagtgtcgga	gaggtaagtg	gaattcctag
661	tgtagcggtg	aaatgcgtag	ataCtaggag	gaacaccagt	ggcgaaggcg	gcttacCgga
721	cgatgactga	cgttgaggct	cgaaagcgtg	gggagcaaac	aggat tagat	accctggtag
781	tccacgccgt	aaacgatgaa	tacùaggtgt	cgggtggcaa	agccattcgg	tgccgcagca
841	aacgcaataa	gtattccacc	tggggagtac	gttcgcaaga	atgaaactca	aaggaattga
901	cggggacccg	cacaagcggt	ggagcatgtg	gtttaattcg	aagcaacgcg	aagaacctta
961	cctgctcttg	acatccccct	gaccggcgtg	taatggtgcc	tttccttcgg	gacaggggag
1021	acaggtggtg	catggttgtc	gtcagcCcgt	gtcgtgagat	gttgggttaa	gtcccgcaac
1081	gagcgcaacc	cttatcttta	gtagccagcg	gtttggccgg	gcactctaga	gagactgcca
1141	gggataacct	ggaggaaggt	ggggatgacg	tcaaatcatc	atgcccctta	tgagcagggc
1201	tacacacgtg	ctacaatggc	gtaaacaaag	ggaggcgaag	ccgtgaggtg	gagcaaatcc
1261	caaaaataac	gtctcagttc	ggattgtagt	ctgcaactcg	actacatgaa	gctggaatcg
1321	ctagtaatcg	cgaatcagaa	tgtcgcggtg	aatacgttcc	cgggtcttgt	acacaccgcc
1381	cgtcacacca	tgggagttgg	taacgcccga	agtcagtgac	ccaaccgcaa	ggagggagct
1441	gccgaaggtg	ggaccgataa	ctggggtgaa	gtcgtaacaa	ggtagccgta	tcggaaggtg
1501	cggctzggatc	acctcctCtc	t

SEQ ID NO:2 (Eubacterium contortum partial 16S rRNA gene, type strain DSM 3982T, clone 2 FR749946) tttgatcctg gctcaggatg aacgccggcg acgtgcttaa cacatgcaag tcgagcgaag cactttactt tgatttcttc ggaatgaaag gttttgtgac tgagcggcgg acgggtgagt

121 aacgcgtggg taacctgcct catacagggg gataacagtt agaaatgact gctaataccg

181 cataagacca cagtaccgca Eggtacagtg ggaaaaacLc cggtggtatg agatggaccc

241 gcgtctgatt agctagttgg taaggtaacg gcttaccaag gcgacgatca gtagccgacc

301 tgagagggtg accggccaca ttgggactga gacacggccc aaactcctac gggaggcagc

361 agtggggaat attgcacaat gggggaaacc ctgatgcagc gacgccgcgt gaaggatgaa

421 gtatttcggt atgtaaactzt ctatcagcag ggaagaaaat gacggtacct gactaagaag

481 ccccggctaa ctacgtgcca gcagccgcgg taatacgtag ggggcaagcg ttatccggat

541 ttactgggtg taaagggagc gtagacggtt atgtaagtct gatgtgaaaa cccggggcùc

601 aaccccggga ctgcattgga aactatgtaa ctagagtgtc ggagaggtaa gtggaattcc

661 tagtgtagcg gtgaaatgcg tagatattag gaggaacacc agtggcgaag gcggcttact

721 ggacgatgac tgacgttgag gctcgaaagc gtggggagca aacaggatta gataccctgg

781 tagtccacgc cgtaaacgat gaatactagg tgtcgggtgg caaagccatt cggtgccgca

841 gcaaacgcaa taagtattcc acctggggag tacgtztcgca agaatgaaac tcaaaggaat

901 tgacggggac ccgcacaagc ggtggagcat gtggtttaat tcgaagcaac gcgaagaacc

ΙΟ

961 ttacctgctc ttgacatccc cctgaccggc gtgtaatggt gcctttcctt cgggacaggg 1021 gagacaggtg gtgcatggtt gtcgtcagct cgtgtcgtga gatgttgggC taagtcccgc 1081 aacgagcgca acccttatct ttagtagcca gcggtttggc cgggcactct agagagactg 1141 ccagggataa cctggaggaa ggtggggatg acgtcaaatc aùcatgcccc ttatgagcag 1201 ggctacacac gtgctacaat ggcgtaaaca aagggaggcg aagccgtgag gtggagcaaa 1261 tcccaaaaat aacgtctcag ttcggattgt agtctgcaac tcgactacat gaagctggaa 1321 tcgctagtaa tcgcgaatca gaatgtcgcg gtgaatacgt tcccgggtct tgtacacacc 1381 gcccgtcaca ccatgggagt tggtaacgcc cgaagtcagt gacccaaccg caaggaggga 1441 gctgccgagg gtgggaccga taactggggt gaagtcgtaa caaggtagcc gtatcggaag 1501 gtgcggctgg atcacctcct ttct

SEQ ID NO:3 (Eubacterium contortum 16S ribosomal RNA ATCC 25540 - L34615)

	1 61	ntcttaacga aagtcgagcg	gagt ttgatc aagcrcttta	ctggctcagg ctCwgatttc	atnaacgctg ttcggawtga	gcggcgtgct arggttttgy	taacacatgc gactgagcgg
15	121	cggacgggtg	agtaacgcgt	gggtaacctg	cctcatacag	ggggataaca	gttagaaatg
	181	actgctaata	ccgcataaga	ccacrgtacc	gcatggtaca	gtggnaaaaa	ctccggtggt
	241	atgagatgga	cccgcgtctg	attagctagt	tggtaaggta	acggcttacn	aaggcgacga
	301	tcagtagccg	acctgagagg	gtgaccggcc	acattgggac	tgagacacgg	ccnnaactcc
	361	tacgggaggc	agcagtgggg	aatattgcac	aacgggggaa	accctgatgc	agcgacgccg
20	421	cgtgaaggat	gaagtatttc	ggtatgtaaa	cttctatcag	cagggaagaa	aatgacggta
	481	cctgactaag	aagccccggc	taactacgtg	ccagcagccn	cggtaatacg	tagggggnna
	541	gcgttatccg	gatttactgg	gtgtaaaggg	agcgtagacg	gttatgtaag	tctgatgtga
	601	aaacccgggg	ctcaaccccn	nnnctgcatt	ggaaactatg	ùaactagagt	gtcggagagg
	661	taagtggaat	tzcctagtgta	gcggtgaaat	gcgtagatat	taggaggaac	accagtggcg
25	721	aaggcggctt	actggacgat	gactgacgt t	gaggctcgaa	agcgtgggga	gcaaacagga
	781	ttagataccc	tggtagtcca	cgccgtaaac	gatgaatact	aggùgtcggg	tggcaaagcc
	841	attcggtgcc	gcagcaaacg	caataagtat	tccacctggg	gagtacgttc	gcaagaatga
	901	aactcaaagg	aattgacggg	naccngcaca	agcggtggag	catgtggttt	aattcgaann
	961	aacgcgaaga	accctacccg	ctcctgacat	ccccctgacc	ggcgtgtaat	ggtgccnttc
30	1021	cttcgggaca	ggggngacag	gtggtgcatg	gttgtcgtca	gctcgtgtcg	tgagatgttg
	1081	ggttaagtcc	cnnaacgagc	gcaaccctta	tctttagtag	ccagcggCtt	aggccggnna
	1141	ctctagagag	actgccaggn	aEaacctgga	ggaaggtggg	gatgacgnnn	aatcatcatg
	1201	ccccttatga	gcaggnctac	acacgtgcta	caatggcgta	aacaaaggga	ggcgaagccg
	1261	ygaggtggag	caaatcccaa	aaataacgtc	tcagttcgga	ttgtagtctg	caactcgact
35	1321	acatgaagct	ggaatcgcta	gtaatcgcga	atcagaatgt	cgcggtgaat	acgttcccnn
	1381	gtcttgtaca	caccgnccgt	cacaccatgg	gagttggtaa	cgcccgaagt	cagtgaccca
	1441	accgcaagga	gggagctgcc	gaaggtggga	ccgataactg	ggg

SEQ ID NO:4 (consensus 16S rRNA sequence for Eubacterium contortum strain MRX050)

TGCAGTCGAGCGAAGCAGCTTTACTTAGATTTCTTCGGATTGAAAGAGTTTTGCGACTGAGCGGCGGACGGGTGAGT

AACGCGTGGGTAACCTGCCTCATACAGGGGGATAACAGTTAGAAATGACTGCTAATACCGCATAAGACCACGGTACC

GCATGGTACAGTGGGAAAAACTCCGGTGGTATGAGATGGACCCGCGTCTGATTAGCTGGTTGGTAAGGTAACGGCTT

ACCAAGGCGACGATCAGTAGCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACG

GGAGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGATGAAGTATTTCG

GTATGTAAACTTCTATCAGCAGGGAAGAAAATGACGGTACCTGACTAAGAAGCCCCGGCTAACTACGTGCCAGCAGC

CGCGGTAATACGTAGGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGACGGTTATGTAAGTCTGA

TGTGAAAACCCGGGGCTCAACCCCGGGACTGCATTGGAAACTATGTAACTAGAGTGTCGGAGAGGTAAGTGGAATTC

CTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGATGACTGACGT

TGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGT

CGGGTGGCAAAGCCATTCGGTGCCGCAGCAAACGCAATAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAAC

TCAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCTG

CTCTTGACATCCCCCTGACCGGCGCGTAATGGTGCCTTTCCTTCGGGACAGGGGAGACAGGTGGTGCATGGTTGTCG

TCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTTTAGTAGCCAGCGGTATGGCC

GGGCACTCTAGAGAGACTGCCAGGGATAACCTGGAGGAAGGTGGGGATGACGTCAAATCATCATGCCCCTTATGAGC

AGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAGGCGAAGCCGCGAGGTGGAGCAAATCCCAAAAATAACGT

CTCAGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGT

GAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTTGGTAACGCCCGAAGTCAGTGACCCAACC GCAAGGAGGGAGCTGCCGAAG

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Claims

1. A composition comprising a bacterial strain of the species Eubacterium contortum, for use in a method of treating or preventing an inflammatory or autoimmune disease, or cancer.

2. The composition of claim l, wherein the composition is for use in a method of treating or preventing a disease or condition selected from the group consisting of uveitis; cancer, including breast cancer, lung cancer, liver cancer, colon cancer, or ovarian cancer; multiple sclerosis; arthritis, including rheumatoid arthritis, osteoarthritis, psoriatic arthritis, or juvénile idiopathic arthritis; neuromyelitis optica (Devic's disease); ankylosing spondylitis; spondyloarthritis; psoriasis; systemic lupus erythematosus; inflammatory bowel disease, including Crolm’s disease or ulcerative colitis; celiac disease; asthma, including allergie asthma or neutrophilie asthma; chronic obstructive pulmonary disease (COPD); scleritis; vasculitis; Behcefs disease; atherosclerosis; atopie dermatitis; emphysema; periodontitis; allergie rhinitis; and allograft rejection.

3. The composition of claim 2, wherein the composition is for use in a method of treating or preventing uveitis.

4. The composition of claim 3, wherein the composition is for use in a method of reducing or preventing retinal damage in uveitis.

5. The composition of claim 2, wherein the composition is for use in a method of treating or preventing cancer, such as lung cancer, breast cancer or liver cancer.

6. The composition of claim 5, wherein the composition is for use in a method of reducing tumour size, reducing tumour growth, preventing metastasis or preventing angiogenesis.

7. The composition of claim 2, wherein the composition is for use in in a method of treating or preventing asthma, such as neutrophilie asthma or allergie asthma.

8. The composition of claim 7, wherein the composition is for use în a method of reducing neutrophilia or eosinophilia in the treatment of asthma.

9. The composition of claim 2, wherein the composition is for use in a method of treating or preventing rheumatoid arthritis.

10. The composition of claim 9, wherein the composition is for use in a method of reducing joint swelling in rheumatoid arthritis.

11. The composition of claim 2, wherein the composition is for use in in a method of treating or preventing multiple sclerosis.

12. The composition of claim 11, wherein the composition is for use in a method of reducing disease incidence or disease severity.

13. The composition of any precedîng claim, wherein the composition is for use in a method of reducing IL-17 production or reducing Thl7 cell différentiation in the treatment or prévention of the inflammatory or autoimmune disease, or cancer.

14. The composition of any preceding claim, wherein the composition is for use in a patient with elevated IL-17 levels or Th 17 cells.

15. The composition of any of ciaims Î-14, for the use of any of ciaims l -14, wherein the bacterial strain has a I6s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO: l, 2, 3 or 4.

16. The composition of claim 15, for the use of claim 15, wherein the bacterial strain has a I6s rRNA sequence that is at least 95%, 96%, 97%, 98%, 99%, 99.5% or 99.9% identical to SEQ ID NO:4, or wherein the bacterial strain has the 16s rRNA sequence represented by SEQ ID NO:4.

17. The composition of any preceding claim, for the use of any preceding claim, wherein the bacterial strain is lyophilised.

18. The composition of any preceding claim, for the use of any preceding claim, wherein the bacterial strain is viable and capable of partially or totally colonising the intestine.

19. The composition of any preceding claim, for the use of any preceding claim, wherein the composition comprises a single strain ofthe species Eubacterium contortum.

20. A food product or vaccine composition comprising the composition of any preceding claim, for the use of any preceding claim.

21. A cell of Eubacterium contortum strain MRX050 deposited as NCIMB 42689.

22. A composition comprising the cell of claim 21.

23. The composition of claim 22, comprising a pharmaceutically acceptable carrier or excipient.

24. A biologically pure culture of Eubacterium contortum strain MRX050 deposited as NCIMB 42689.

25. A cell of the Eubacterium contortum strain MRX050 deposited as NCIMB 42689, for use in therapy.

26. The cell of claim 25, wherein the cell is for use in a method defined in any of ciaims 1-14.

27. A composition comprising one or more bacterial strains of the species Eubacterium contortum, which does not contain bacteria from any other genus or which comprises only de minimis or biologically irrelevant amounts of bacteria from another genus, for use in therapy.

28. A composition comprising one or more bacterial strain of the species Eubacterium contortum, for use in therapy.