Therapeutic bacterial compositions

Abstract

The invention relates to composition for use in treating or preventing radiation induced gastrointestinal toxicities, using bacteria. The invention also relates to methods of treating or preventing radiation induced gastrointestinal toxicities.

Description

[0001] Therapeutic bacterial compositions

[0002] Introduction

[0003] Cancer radiotherapy is widely used for the treatment of solid tumors, such as colorectal cancer. Unfortunately, patients treated with radiation are commonly affected by gastrointestinal toxicity (radiation enteritis).

[0004] Radiation enteritis is a bowel injury resulting from radiotherapy of malignancies in the abdominal or pelvic regions. It affects almost 90% of patients undergoing radiotherapy, with up to 10% suffering from severe forms of enteritis [1], The high turnover rates of small intestinal and colonic epithelia, estimated to be the highest amongst fixed tissues [2], render them prone to radiation injury. This sensitivity is translated in the radiation-induced increase of gut epithelial permeability and abrogation of expression of tight junction proteins [3,4,5], Moreover, gut microbiome dysbiosis has been associated with radiation enteritis in patients exposed to pelvic radiation. Patients suffering from radiation enteritis displayed signs of dysbiosis [6], Dysbiosis correction through fecal microbiome transplantation (FMT) has been revealed to protect against radiation-induced gut injury in a radiation mouse model. This was demonstrated by enhanced barrier function and increase in mucin production [7], Interestingly, the efficacy of FMT in relieving radiation-induced enteritis was demonstrated in a pilot study with cancer patients [8], In conclusion, structuring the microbiome to be supportive of gut epithelial barrier can be beneficial for the treatment of radiation enteritis.

[0005] Preparations that contain a defined bacterial mixture that contain a single strain of gut commensal bacteria or a mixture of strains are generally accepted to be a safer treatment than FMT.

[0006] Thus, there is a need for bacterial compositions comprising isolated bacteria that can be used in the treatment of radiation enteritis. The present invention is aimed at addressing this need. The present invention thus provides bacterial compositions that improve epithelial barrier function and the detrimental effects of radiation. The bacterial compositions can alleviate the toxicities of radiotherapy treatment in cancer patients.

[0007] Summary of the invention

[0008] In a first aspect, the invention relates to a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae for use in the treatment or prevention of radiation induced gastrointestinal toxicities prior to, during or after cancer treatment with radiotherapy, e.g. treatment or prevention of radiation enteritis. The invention also relates to a method for treating or preventing radiation induced gastrointestinal toxicities, prior to, during or after cancer treatment with radiotherapy, e.g. treatment or prevention radiation enteritis, comprising administering a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae to a subject.

[0009] Description of Figures

[0010] The invention is illustrated in the following non-limiting figures.

[0011] Figure 1. Bacterial composition protects epithelial barrier and prohibit macrophage activation. The ability of bacterial composition to impair translocation of heat-killed bacteria and the subsequent activation of macrophages, was determined by co-culturing a monolayer of Caco-2 cells on the insert of a transwell system with the bacteria in anaerobic conditions at a concentration of 107colony-forming units (CFU) / ml for 24 hours. The bacteria were then washed, and monocyte-derived macrophages were added to the lower chamber of the transwell system. Next, heat-killed Salmonella typhimurium was added on top of the Caco-2 monolayer and its translocation and activation of macrophages was determined by measuring the inflammatory cytokines IL-1β, IL-6 and TNF-a in 24 hours macrophage supernatants by ELISA. No treatment (grey bar) and treatment Salmonella typhimurium (black bar) were used as controls. Results are the mean ± SEM of 2 macrophage donors with 4 technical replicates each in one experiment.

[0012] Figure 2. Bacterial consortium repairs DSS-induced epithelial permeability. Dissociated colonic organoids were seeded in a transwell. Once a tight monolayer was formed, the cells were treated with DSS (8%) for 24 hours, followed by co-culture with the bacterial composition (DSS+CONS, grey bar) for another 24 hours. FITC-Dextran was added to the upper compartment of the transwell. After 4 hours fluorescence was measured in the lower compartment of the transwell. Untreated organoid cells (Control, black bar), DSS only treated organoid cells (DSS, white bar) and empty transwells (No cell, striped bar) were included. Permeation rate (apical fluorescence / basal fluorescence) is depicted in the bar graph. Results are the mean ± SEM of 3 organoid lines in 2 independent experiments.

[0013] Figure 3. Bacterial composition promotes cell adhesion protein expression in radiation enteritis organoid model. The ability of bacterial composition to protect epithelial barrier function from the effects of radiation was determined in a human colonic organoid model. These organoids were injected luminally with the bacterial composition. After 24 hours, bacterial-containing organoids (green bars) and empty organoids (red bars, second bar on the left in each cohort) were irradiated with a total dose of 10 Gy. None injected, none irradiated control organoids (blue bars, first bar on the left in each cohort) were taken along. The expression of tight junction proteins in the different types of organoids was determined by real time PCR 48 hours following radiation. The results are presented as the mean ± SEM of 2 independent experiments, using 3 different organoid lines. * Adjusted p-value < 0.05 (2-way ANOVA with FDR).

[0014] Figure 4. Bacterial composition promotes organoid regeneration and stem cell activity in radiation enteritis model. The ability of bacterial composition to protect the sternness and regeneration capacity of the epithelial barrier, following exposure to radiation, was determined in a human colonic organoid model. These organoids were injected by the bacterial composition. After 24 hours, bacterial-containing organoids (green bars) and empty organoids (red bars, second bar on the left in each cohort) were irradiated with a total dose of 10 Gy. None injected, none irradiated control organoids (blue bars, first bar on the left in each cohort) were taken along. The phenotype of the organoids was determined by microscopy, 48 hours following radiation (A). The expression of the stem cell marker LGR5 in the different types of organoids was determined by real time PCR 48 hours following radiation (B). The results are presented as the mean ± SEM of 2 independent experiments, using 3 different organoid lines. * Adjusted p-value < 0.05; ** Adjusted p-value < 0.005 (2-way ANOVA with FDR).

[0015] Figure 5. Different combinations of individual strains of bacterial composition promote expression of adhesion proteins and stem cell activity marker, a) to i) show different proteins / markers. The ability of different combinations of the different strains of the bacterial composition to protect epithelial barrier function from the effects of radiation was determined in a human colonic organoid model. These organoids were injected luminally with the bacterial compositions. After 24 hours, bacterial-containing organoids (green bars) and empty organoids (red bars “IR”, second bar on the left in each panel) were irradiated with a total dose of 10 Gy. Non-injected, non-irradiated control organoids (blue bars “control”, first bar on the left in each panel) were taken along. The expression of tight junction proteins and stem cell marker Lgr5 in the different types of organoids was determined by real time PCR 48 hours following radiation. The results are presented as the mean ± SEM of two technical replicates of a single experiment.

[0016] Detailed description

[0017] The present invention will now be further described. In the following passages, different aspects of the invention are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

[0018] Generally, nomenclatures used in connection with, and techniques of microbiology, cell and tissue culture, pathology, molecular biology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed according to conventional methods well-known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N. Y. (2012).

[0019] The nomenclatures used in connection with, and the laboratory procedures and techniques of analytical chemistry, microbiology, bioinformatics and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art.

[0020] The inventors have identified bacteria that can be used in preventing and / or treating radiation induced gastrointestinal (Gl) toxicities, e.g. radiation enteritis.

[0021] Thus, the invention relates to therapeutic bacterial compositions comprising one or more, e.g. a consortium of defined bacterial isolates for use in preventing or treating radiation induced gastrointestinal (Gl) toxicities, e.g. radiation enteritis and related methods.

[0022] The term radiation induced gastrointestinal (Gl) toxicities refers to a condition that results from the exposure to radiation. Damage to the small and / or large intestines occurs as a toxic side effect secondary to radiation. Radiation exposures can result from environmental, accidental, medical, or terrorist radiation / nuclear incidents. Possible non-limiting radiation sources include gamma, neutron, X-rays, proton beam and radioactive isotopes.

[0023] One example is radiation enteritis.

[0024] In particular, according to the invention, radiation enteritis refers to a condition that affects the gastrointestinal tract, e.g. intestine, bowel, pelvis and / or abdomen and results from the exposure of a subject’s body to radiation during radiation therapy for cancer treatment.

[0025] Radiation enteritis is generally classified as early (acute) when it occurs within 3 months of radiation therapy or delayed (chronic) when it occurs more than 3 months after radiation therapy. Symptoms of early bowel toxicity include nausea, abdominal pain, diarrhoea and fatigue.

[0026] The terms radiation colitis, radiation enteropathy, radiation mucositis, radiation-induced gastrointestinal syndrome (RIGS) and intestinal radiation toxicity can all be used as alternative terms to describe the condition. Radiation enteritis is a common side effect of radiotherapy and can occur during the treatment of various cancers with radiotherapy, including but not limited to cancers that occur in the abdominal and pelvic area.

[0027] The cancer can be selected from a solid or non-solid tumour.

[0028] In one embodiment, the cancer is a cancer that is treated by radiation therapy. In particular, radiation therapy is used to treat cancers that occur in the abdominal and pelvic area. Such cancers include bowel, cervical, pancreatic, prostate, uterine, colon, peritoneum (abdominal lining), stomach, renal, ovarian, testicular, uterus, bladder and rectal cancer.

[0029] The cancer may be a primary cancer or secondary, i.e. metastatic tumour. Metastasis occurs when a cancer spreads beyond the place where it started to other areas of the body via the bloodstream or lymphatic system. Nearly all cancers have the potential to metastasize. Some of the most common sites of metastases are the adrenal glands, bones, brain, liver, lungs, lymph nodes and peritoneum.

[0030] In one embodiment, the cancer may be a metastatic cancer, i.e. a cancerthat originates from a cancer treated with radiation therapy. For example, metastatic stomach cancer is a malignancy that originated in the stomach and has spread to other areas of the body. Most commonly, stomach cancer that has reached this advanced stage may have spread to the liver, peritoneum, lungs, or bones. Ovarian cancer for example may lead to secondary breast, bladder, bile duct cancer, melanoma of the eye or acute leukemia. The most common places for bowel cancer to spread are the liver and the lungs.

[0031] Therefore, according to the invention, the cancer may be selected from a gastrointestinal cancer, skin cancer, e.g. melanoma, bone cancer, pancreatic cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, bile duct cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, brain cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas.

[0032] In one embodiment, the tumour is a solid tumour. Examples of solid tumours which may be accordingly treated include breast carcinoma, lung carcinoma, colorectal carcinoma, pancreatic carcinoma, glioma and lymphoma. Some examples of such tumours include epidermoid tumours, squamous tumours, such as head and neck tumours, colorectal tumours, prostate tumours, breast tumours, lung tumours, including small cell and non-small cell lung tumours, pancreatic tumours, thyroid tumours, ovarian tumours, and liver tumours. Other examples include Kaposi's sarcoma, CNS, neoplasms, neuroblastomas, capillary hemangioblastomas, meningiomas and cerebral metastases, melanoma, gastrointestinal and renal carcinomas and sarcomas, rhabdomyosarcoma, glioblastoma, preferably glioblastoma multiforme, and leiomyosarcoma. Examples of vascularized skin cancers for which the antagonists of this invention are effective include squamous cell carcinoma, basal cell carcinoma and skin cancers that can be treated by suppressing the growth of malignant keratinocytes, such as human malignant keratinocytes. In one embodiment, the cancer is NSCSL.

[0033] In one embodiment, the tumour is a non-solid tumour. Examples of non-solid tumours include leukemia or multiple myeloma.

[0034] In one embodiment, the cancer is selected from colorectal, gastric, oesophageal, anal, testicular, prostate, breast, ovarian, endometrial, cervical, bladder, pancreatic, liver, lung, skin, bone, head and neck, brain, thyroid, oral, lymphomas, myelomas or sarcomas.

[0035] In reference to cancer, an effective amount may comprise an amount sufficient to cause a tumour to shrink and / or to decrease the growth rate of the tumour (such as to suppress tumour growth) or to prevent or delay other unwanted cell proliferation. In some embodiments, an effective amount is an amount sufficient to delay development or prolong survival or induce stabilisation of the cancer or tumour. In some embodiments, a therapeutically effective amount is an amount sufficient to prevent or delay recurrence. For example, a "therapeutically effective dosage" may induce tumour shrinkage by at least about 5% relative to baseline measurement, such as at least about 10%, or about 20%, or about 60% or more. The baseline measurement may be derived from untreated subjects.

[0036] The bacterial compositions as used according to the invention include isolated bacteria and are not therefore faecal microbiota transplants (FMT). Faecal microbiota transplants include a mixture of undefined, unselected bacteria and faecal material. In contrast, the composition of the various aspects of the invention contains mixtures of defined bacterial isolates free of faecal material. Preparations that contain a defined isolated bacterial mixture are generally accepted to be a safer treatment than FMT. An advantage of the present compositions is that they comprise only selected, defined and characterised bacteria and no undefined or unwanted components, which may be present in donor stools, thereby allowing the therapeutic composition to be standardised and increasing safety of the composition. Thus, the invention excludes administration of faecal transplants.

[0037] FMT relies on a stool sample from a healthy human donor which is administered directly to the recipient, e.g. via colonoscopy, without bacteria present in the stool sample being isolated prior to the administration of the FMT to the recipient. While FMT is widely used, there are some disadvantages associated with FMT. The composition of the FMT material is very donor dependant and therefore is inconsistent. Despite screening of donors, it is difficult to determine the bacterial load of the samples. Donors also have to be screened for pathogens and to assess the risk of colonization with drug-resistant bacteria. Additionally, the manufacture and supply of FMT presents logistic challenges and is not readily scalable as a pharmaceutical product. In contrast to FMT treatment, which uses non-selected and nonisolated bacteria, the present invention is based on the use of isolated bacteria that have been selected.

[0038] The compositions as used according to the invention include isolated bacteria. The term "isolated" refers to bacteria that are isolated from the natural environment or samples. The isolated bacteria, e.g. isolated bacterial strains, are substantially free of other cellular material, chemicals and / or faecal material. Thus, as used herein, the term “isolated” bacteria refers to bacteria that have been separated from one or more undesired component, such as another bacterium or bacterial strain, one or more component of a growth medium, and / or one or more component of a sample, such as a faecal sample. In some embodiments, the bacteria are substantially isolated from a source such that other components of the source are not detected.

[0039] In certain aspects described below, the invention also relates to augmenting FMT therapy for treating radiation enteritis with one or more bacterial isolate from one or more family, genus or species as disclosed herein.

[0040] As used herein, the term “species” refers to a taxonomic entity as conventionally defined by genomic sequence and phenotypic characteristics. A “strain” is a particular instance of a species that has been isolated and purified according to conventional microbiological techniques. It will be understood that the terms bacteria and bacterial isolates as used herein refer to a plurality of bacteria, that is a bacterial population.

[0041] In one embodiment, the bacteria of the compositions are metabolically inactive prior to administration. For example, the bacteria are lyophilised. In one embodiment, the composition includes vegetative bacterial cells and does not include bacterial spores. In one embodiment, the composition includes vegetative bacterial cells and / or bacterial spores. In one embodiment, the composition includes bacterial spores and does not include vegetative bacterial cells. In one embodiment, the composition includes vegetative bacterial cells and does not include bacterial spores or is substantially devoid of spores. In one embodiment, the composition includes fewer than about 0.1%, 0.5%, 1%, 2%, 3%, 4% or 5% spores. In one embodiment, the isolated bacteria, e.g. isolated bacterial strains, from the species listed herein, can be viable bacteria that are capable of colonising the gastrointestinal gut of a subject when administered to said subject.

[0042] The compositions can be described as a live bacterial product or a live biotherapeutic product. As described herein, a live bacterial product (also referred to as a bacterial composition, a live bacterial consortium, or bacterial consortium) comprises one or more isolated live bacteria; e.g. bacterial strains from one or more bacterial species as described herein. The term “live bacterial therapy” is interchangeably used herein with live biotherapeutic product and bacteriotherapy herein and defines a therapy using live bacteria to restore health or alleviate disease I disease symptoms or increase response to a therapy.

[0043] The bacterial compositions comprising single or multiple strains of one species or mixtures of single or multiple strains from one or more species are selected based on the ability of the strain and / or live bacterial product to induce or stimulate a desired response when administered to a subject (e.g., a cancer patient). The bacterial compositions thus provide a therapeutic effect I mechanisms relevant to therapy.

[0044] In a first aspect, the invention relates to a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae for use in the treatment or prevention of radiation induced Gl toxicities, e.g. radiation enteritis.

[0045] The invention also relates to the use of isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae in the manufacture of a medicament for the treatment or prevention of radiation induced Gl toxicities, e.g. radiation enteritis.

[0046] In one embodiment of these aspects, the composition is administered prior to, concurrent with or after radiation therapy.

[0047] The invention also relates to a method for treating or preventing radiation induced Gl toxicities, e.g. radiation enteritis, comprising administering a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae to a subject in need thereof.

[0048] In one embodiment, the composition is administered prior to, concurrent with or after radiation therapy.

[0049] Thus, according to these aspects of the invention, bacteria from one or more of these families can be used in the composition. Embodiments of the composition for use in treatment or prevention / the composition used in methods of treatment or prevention

[0050] The following further describes the composition for use in treatment or prevention of radiation induced Gl toxicities and used in the methods of treatment or prevention of radiation induced Gl toxicities according to the invention.

[0051] The composition comprises or consists of bacteria from one bacterial family or from 2, 3 or 4 different bacterial families that are described herein, namely Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae. Any combinations of families are within the scope of the invention.

[0052] A composition used according to some aspects of the invention, including methods of treatment, comprises one or more bacterial family, genus or species selected from those listed in Table 1. The ability of the specific bacteria or the combination of bacteria of the live bacterial product to induce a beneficial effect, e.g. an effect useful in the treatment of radiation induced Gl toxicities, e.g. radiation enteritis, can be assessed using any of method known in the art, e.g., in vitro assays for example using cell culture, e.g. organoids, or in vivo studies. Exemplary assays are described in the examples.

[0053] In one embodiment, the isolated bacteria, e.g. isolated bacterial strains, can be viable bacteria that are capable of colonising and / or engraftment of the gastrointestinal gut of a subject when administered to said subject.

[0054] The inventors have shown that by using certain bacteria, e.g. by combining bacteria from different species, a therapeutic composition can be provided which finds use as a treatment of radiation induced Gl toxicities, e.g. radiation enteritis.

[0055] Thus, in a first aspect, the composition comprising one, two or more isolated bacteria, e.g. a bacterial strain, selected from one or more of the bacterial families, genera or species as listed in Table 1. For example, the composition comprises one or more bacterial isolate, e.g. bacterial population, having a 16SrDNA selected from SEQ ID. Nos 1 to 11 or a sequence with at least 80%, 90%, 95% or 98.7% sequence identity thereto. In one embodiment, sequence identity is 98.7%.

[0056] Table 1 below lists the 4 bacterial families, genera or species from which the isolated bacteria present in the composition are selected. Reference to exemplary 16S rDNA sequence characterising each species is also provided. The terms 16S rDNA sequence or 16S rDNA as used herein refer to DNA nucleic acid sequences, i.e. a nucleic acid molecule, which encodes 16S rRNA nucleic acid sequence i.e. a nucleic acid molecule. Nucleic acid sequences are listed in Table 4. Also, as explained further below, the bacteria of the composition may have a 16S rDNA sequence with certain sequence identity to the SEQ ID Nos listed below. Thus, in one embodiment, the composition comprises or consists of a population of bacteria from 1, 2, 3 or 4 families, genera or species as defined by the species name. Additionally or alternatively, the bacteria can be defined by reference to the SEQ ID No. as in Table 1 and as explained further herein. Also, as explained further below, the bacteria of the composition may have a 16S rDNA sequence with certain sequence identity to the SEQ ID Nos. as listed below.

[0057] As used herein, when describing a sequence that has certain sequence percentage identity to a reference SEQ ID NO, the full length 16S rDNA sequence has the recited sequence identity with the full length of the reference sequence.

[0058] Table 1. Bacteria

[0059] No Taxonomy Family Taxonomy genus Taxonomy 16s rDNA Possible alternative Example species sequence - taxonomy: exemplary closely related sequence

[0060] species based on closely related bacteria identified from public databases, or given name B1 Coriobacteriaceae Senegalimassilia Senegalimassilia SEQ ID NO. na anaerobia 1, SEQ ID

[0061] NO. 5

[0062] B2 Christensenellaceae Christensenella Christensenellaceae SEQ ID NO. Powria foxae, (also referred to as R-7 group sp. 2, SEQ ID Clostridiales Aristaeellaceae) NO. 6, SEQ bacterium P40,

[0063] ID NO. 7 UBA11524 sp000437595 B3 Prevotellaceae Prevotella Prevotella copri SEQ ID NO. Segatella copri 3, SEQ ID

[0064] NO. 8, SEQ

[0065] ID NO. 9,

[0066] SEQ ID NO.

[0067]

[0068] B4 Barnesiellaceae Barnesiella Barnesiella SEQ ID NO. na intestinihominis 4, SEQ ID

[0069] NO. 11, SEQ

[0070] ID NO. 26-28

[0071]

[0072] na = not available

[0073] Table 1 provides reference to families, exemplary genera, exemplary species and exemplary strains for the bacterial species (provided by reference to 16S rDNA). Certain embodiments of the invention described herein are defined by reference to the species name and / or SEQ ID NO. as shown in Table 1. In some cases, different exemplary sequences are provided in Table 1 for the same species, e.g. corresponding to different exemplary strains which belong to the same species. Where multiple sequences are provided for a species, these sequences share a high sequence identity, e.g. the different strains of the same species have at least 98.7% sequence identity.

[0074] In one aspect of the invention, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Barnesiellaceae and / or Prevotellaceae. Thus, the composition comprises or consists of bacteria from one family or comprises or consists of bacteria from 2, 3 or 4 different families as recited herein.

[0075] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae. In one embodiment, the composition comprises or consists of bacteria belonging to the family Christensenellaceae. In one embodiment, the composition comprises or consists of bacteria belonging to the family Prevotellaceae. In one embodiment, the composition comprises or consists of bacteria belonging to the family Barnesiellaceae.

[0076] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, Christensenellaceae and Prevotellaceae.

[0077] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, Christensenellaceae and Barnesiellaceae.

[0078] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, Prevotellaceae and Barnesiellaceae.

[0079] In one embodiment, the composition comprises or consists of bacteria belonging to the family Christensenellaceae, Prevotellaceae and Barnesiellaceae. In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae and Christensenellaceae.

[0080] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, and Prevotellaceae.

[0081] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae and Barnesiellaceae.

[0082] In one embodiment, the composition comprises or consists of bacteria belonging to the family Christensenellaceae and Prevotellaceae.

[0083] In one embodiment, the composition comprises or consists of bacteria belonging to the family Christensenellaceae and Barnesiellaceae.

[0084] In one embodiment, the composition comprises or consists of bacteria belonging to the family Prevotellaceae and Barnesiellaceae.

[0085] In one embodiment, the composition comprises or consists of bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Barnesiellaceae and Prevotellaceae.

[0086] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and / or Barnesiella.

[0087] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia. In one embodiment, the composition comprises or consists of bacteria belonging to the genus Christensenella. In one embodiment, the composition comprises or consists of bacteria belonging to the genus Prevotella. In one embodiment, the composition comprises or consists of bacteria belonging to the genus Barnesiella.

[0088] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and Barnesiella.

[0089] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia, Christensenella and Prevotella.

[0090] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia, Christensenella and Barnesiella. In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia, Prevotella and Barnesiella.

[0091] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Christensenella, Prevotella and Barnesiella.

[0092] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia and Christensenella.

[0093] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia and Prevotella.

[0094] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Senegalimassilia and Barnesiella.

[0095] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Christensenella and Prevotella.

[0096] In one embodiment, the composition comprises or consists of Christensenella and Barnesiella.

[0097] In one embodiment, the composition comprises or consists of bacteria belonging to the genus Prevotella and Barnesiella.

[0098] In one embodiment, the composition comprises or consists of bacteria selected from Senegalimassilia anaerobia, Christensenellaceae R-7 group sp., Prevotella copri and / or Barnesiella intestinihominis. In one embodiment, the composition comprises or consists of Senegalimassilia anaerobia bacteria. In one embodiment, the composition comprises or consists of Christensenellaceae R-7 group sp. bacteria. In one embodiment, the composition comprises or consists of Prevotella copri bacteria. In one embodiment, the composition comprises or consists of Barnesiella intestinihominis bacteria. In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Prevotella copri.

[0099] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Barnesiella intestinihominis.

[0100] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis. In one embodiment, the composition comprises or consists of bacteria from the species Christensenellaceae R-7 group sp. Prevotella copri and Barnesiella intestinihominis.

[0101] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia and Christensenellaceae R-7 group sp.

[0102] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia and Prevotella copri.

[0103] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia and Barnesiella intestinihominis.

[0104] In one embodiment, the composition comprises or consists of bacteria from the species Christensenellaceae R-7 group sp. and Prevotella copri.

[0105] In one embodiment, the composition comprises or consists of bacteria from the species Christensenellaceae R-7 group sp. and Barnesiella intestinihominis.

[0106] In one embodiment, the composition comprises or consists of bacteria from the species Prevotella copri and Barnesiella intestinihominis.

[0107] In one embodiment, the composition comprises or consists of bacteria from the species Senegalimassilia anaerobia, Christensenellaceae R-7 group sp., Prevotella copri and Barnesiella intestinihominis.

[0108] Other examples of species in the genus Senegalimassilia include Senegalimassilia anaerobia and Senegalimassilia faecalis.

[0109] Other examples of species in the genus Christensenella include Christensenella hongkongensis, Christensenella intestinihominis, Christensenella massiliensis, Christensenella minuta, Christensenella tenuis and Christensenella timonensis.

[0110] Other examples of species in the genus Prevotella include Prevotella albensis, Prevotella amnii, Prevotella aurantiaca, Prevotella avicola, Prevotella baroniae, Prevotella bergensis, Prevotella bivia, Prevotella brevis, Prevotella brunnea, Prevotella bryantii, Prevotella buccae, Prevotella buccalis, Prevotella cerevisiae, Prevotella colorans, Prevotella communis, Prevotella conceptionensis, Prevotella copri, Prevotella corporis, Prevotella dentalis, Prevotella dentasini, Prevotella denticola, Prevotella disiens, Prevotella enoeca, Prevotella equi, Prevotella falsenii, Prevotella fusca, Prevotella heparinolytica, Prevotella herbatica, Prevotella histicola, Prevotella hominis, Prevotella ihumii, Prevotella illustrans, Prevotella intermedia, Prevotella intestinigallinarum, Prevotella jejuni, Prevotella koreensis, Prevotella lacticifex, Prevotella lascolaii, Prevotella loescheii, Prevotella maculosa, Prevotella marseillensis, Prevotella marshii, Prevotella massiliensis, Prevotella melaninogenica, Prevotella merdae, Prevotella micans, Prevotella mizrahii, Prevotella multiformis, Prevotella multisaccharivorax, Prevotella nanceiensis, Prevotella nigrescens, Prevotella oralis, Prevotella oris, Prevotella oryzae, Prevotella oulora, Prevotella oulorum, Prevotella pallens, Prevotella paludivivens, Prevotella pectinovora, Prevotella phocaeensis, Prevotella pleuritidis, Prevotella rara, Prevotella rectalis, Prevotella ruminicola, Prevotella saccharolytica, Prevotella salivae, Prevotella scopos, Prevotella shahii, Prevotella stercorea, Prevotella stercoripullorum, Prevotella tannerae, Prevotella timonensis, Prevotella veroralis, Prevotella vespertina and Prevotella zoogleoformans.

[0111] Other examples of species in the genus Barnesiella include Barnesiella excrementavium, Barnesiella excrementigallinarum, Barnesiella excrementipullorum, Barnesiella faecis, Barnesiella intestinihominis, Barnesiella merdigallinarum, Barnesiella merdipullorum, Barnesiella propionica or Barnesiella viscericola.

[0112] Exemplary sequences of bacterial species that can be used in the composition, alone or in combination, are shown in SEQ ID Nos 1 to 11 and 26-28. Also within the scope of the invention are compositions for use and methods as described herein wherein the composition comprises bacterial species that comprise a 16S rDNA sequence having a SEQ ID Nos selected from 1 to 11 and 26-28 or a sequence having at least 80%, 85%, 90%, 95% or 98.7% or 99% sequence identity thereto

[0113] In the aspects and embodiments described herein, for each of B1 to B4 as shown in Table 1, any of the sequences defined herein and listed in Table 1 can be used. Thus, where multiple sequences are provided for a single species, any of these sequences or a mixture can be used. According to various embodiment of the invention, the composition comprises bacteria from one or more bacterial species, e.g. 2, 3 or species, genus or family as shown in Table 1 comprising a 16S rDNA sequence as shown in Table 1 and Table 4 or a sequence having at least 80%, 85%, 90%, 95% or 98.7% or 99% sequence identity thereto.

[0114] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2.

[0115] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA according to SEQ ID NO: 1 or 5 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2.

[0116] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3.

[0117] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3.

[0118] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 4.

[0119] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5 and bacteria comprising the 16S rDNA according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0120] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3.

[0121] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3.

[0122] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0123] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2 and bacteria comprising the 16S rDNA according to SEQ ID NO: 4.

[0124] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0125] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0126] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5 a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 and comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1, a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2 and comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3.

[0127] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7 and comprising bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2 and comprising bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3.

[0128] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 and comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1, comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2 and comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0129] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7 and comprising a 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0130] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0131] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0132] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0133] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7, bacteria comprising the 16S rDNA according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0134] In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5, a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1, a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3 and bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4.

[0135] In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1 or 5, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, 6 or 7, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3, 8, 9 or 10 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. In one embodiment, the composition comprises or consists of bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 1, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 2, bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 3 and bacteria comprising the 16S rDNA sequence according to SEQ ID NO: 4.

[0136] In some embodiments, the live bacterial product comprises one or more bacterial strains of each of the 4 recited species above. It should be appreciated that the strains provided are exemplary strains and that closely related bacterial strains of the same species (e.g., as defined by 16S rDNA sequences and certain sequence percentage identity, e.g. 98.7%) have highly similar or the same biological properties. It would therefore be apparent to the skilled person that bacterial strains listed above can be replaced with bacterial strains of the same species. The invention is not limited to the exemplary strains.

[0137] In one embodiment, the composition comprises or consists of 4 different isolated bacteria, i.e. bacteria from each of the 4 bacterial families, genera or species described above and in Table 1, for example with reference to the sequences as shown in Table 1 or a sequence with identity thereto as explained herein. In one embodiment, the composition comprises subsets I combinations of bacterial species listed in Table 1. Subsets I combinations of isolates from different bacterial species are also provided.

[0138] In one embodiment, the composition does not comprise bacteria of any other family, genus or species, i.e. a species not listed in Table 1, orthe composition comprises only de minimis or biologically irrelevant amounts of bacteria from another species not listed in Table 1. By biologically irrelevant is meant bacteria that do not have an effect on the treatment of radiation induced Gl toxicities, e.g. radiation enteritis. However, the composition may comprise further components that are not bacteria, e.g. pharmaceutical carriers and the like.

[0139] In another embodiment, the composition may comprise other bacterial species that fall within a family or genus listed in Table 1, but does not comprise bacterial species of a family or genus not listed in Table 1. However, the composition may comprise further components that are not bacteria, e.g. pharmaceutical carriers and the like.

[0140] In another embodiment, the composition may comprise other bacterial species, i.e. bacteria of a family, genus or species bacterial species not listed in Table 1.

[0141] In one embodiment, the composition includes further bacteria belonging to the family Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae, Ruminococcaceae and / or Lachnospiraceae.

[0142] In one embodiment, the composition includes further bacteria belonging to the genus Bifidobacterium, Eubacterium, Bacteroides, Ruminococcus and / or Roseburia. In one embodiment, further bacteria the further bacteria are selected from Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Eubacterium ventriosum, Bacteroides stercoris and / or Roseburia faecis bacteria.

[0143] In one embodiment, the composition includes further bacteria the further bacteria comprise Slackia isoflavoniconvertens.

[0144] In one embodiment, the composition includes further bacteria having a comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence selected from according to SEQ ID NO: 12 to 25.

[0145] As will be apparent to a skilled person, one or a number of bacterial species selected from those listed in Table 1 can be combined in a single composition. For example, the composition comprises or consists of at least 1 or 2, e.g. up to 3, up to 4, isolated bacterial species selected from those shown in table 1, for example with reference to the sequences as shown in the table. Examples of combinations of bacterial species are set out below. One or more strain can be used for each species.

[0146] In one embodiment, the composition comprises at least 1, at least 2, at least 3 or at least 4 different isolated bacterial species selected from those listed in table 1, for example with reference to the sequences as shown in Table 4.

[0147] In one embodiment, the composition comprises or consists of no more than 2, no more than 3 or no more than 4 different isolated bacterial species selected from those listed in table 1, for example with reference to the sequences as shown in Table 4.

[0148] In one embodiment, the composition comprises or consists of 1, 2, 3 or 4 different isolated bacterial species selected from those listed in table 1, for example with reference to the sequence IDs as shown in Tables 1 and 4.

[0149] A skilled person would appreciate that that bacterial species selected from Table 1 and for use in the composition and methods of the invention can have the sequence shown in Table 4 or a sequence that has certain percentage identity thereto and retains biological activity; i.e. activity against radiation enteritis, e.g. reduction of symptoms of radiation enteritis.

[0150] Methods of determining sequence identity are known in the art. It is known that clades, operational taxonomic units (OTUs), species, and strains are, in some embodiments, identified by their 16S rDNA sequence. The relatedness can be determined by the percent identity and this can be determined using methods known in the art. Bacterial species and strains used in a composition as described herein can be identified based on the 16S nucleic acid sequence (full length or part thereof, such as V regions). The 16S ribosomal DNAgene codes for the DNA component of the 30S subunit of the bacterial ribosome. It is widely present in all bacterial species. Different bacterial species have one to multiple copies of the 16S rDNA gene, and copies of the 16S rDNA gene may differ in sequence within the same bacterium. Bacteria usually carry multiple copies of a 16S rDNA gene. 16S rDNA gene sequencing is by far one of the most common methods targeting housekeeping genes to study bacterial phylogeny and genus / species classification. Thus, bacteria can be taxonomically classified based on the sequence of the gene encoding the 16S nucleic acid sequence, e.g. ribosomal DNA (rDNA) in the bacterium. This gene sequence is also referred to as the ribosomal DNA sequence (rDNA). The bacterial 16S rDNA is approximately 1500 nucleotides in length and is used in reconstructing the evolutionary relationships and sequence similarity of one bacterial isolate to another using phylogenetic approaches. 16S rDNA sequences are used for phylogenetic reconstruction as they are in general highly conserved, but contain specific hypervariable regions that harbour sufficient nucleotide diversity to differentiate genera and species of most microbes.

[0151] Using well known techniques to determine a full 16S rDNA sequence or the sequence of any hypervariable region of the 16S rDNA sequence, genomic DNA is extracted from a bacterial sample, the 16S rDNA (full region or specific hypervariable regions) amplified using polymerase chain reaction (PCR), the PCR products cleaned, and nucleotide sequences delineated to determine the genetic composition of 16S rDNA gene or subdomain of the gene. If full 16S rDNA sequencing is performed, the sequencing method used may be, but is not limited to, Sanger sequencing. If one or more hypervariable regions are used, such as the V4 region, the sequencing may be, but is not limited to being, performed using the Sanger method or using a next-generation sequencing method, such as an Illumina (sequencing by synthesis) method using barcoded primers allowing for multiplex reactions. Next generation whole genome sequencing can be used to obtain the sequence of each 16S rDNA gene within a bacterial genome, when multiple copies of the gene are present. The V1-V9 regions of the 16S refer to the first nine hypervariable regions of the 16S rDNA gene that are often used for genetic typing of bacterial samples. Gene sequences are presented herein using letter representation to specific nucleotides, i.e. A, T, G, C. Polymorphisms in 16S rDNA gene sequence copies within a bacterium can be represented using IUPAC codes.

[0152] In some embodiments, bacterial species identified as described herein are identified by sequence identity to 16S rDNA sequences as known in the art and described herein. In some embodiments, the selected species are identified by sequence identity to full length 16S rDNA sequences as shown in Table 4. As used herein, the terms "homology" or “identity” generally refer to the percentage of nucleic acid residues in a sequence that are identical with the residues of the reference sequence with which it is compared, after aligning the sequences and in some embodiments after introducing gaps, if necessary, to achieve the maximum percentage homology, and not considering any conservative substitutions as part of the sequence identity. Thus, the percentage homology between two nucleic acid sequences is equivalent to the percentage identity between the two sequences. Methods and computer programs for the alignment are well known. The percentage identity between two sequences can be determined using well known mathematical algorithms, such as the Smith Waterman algorithm.

[0153] In one embodiment, the degree of sequence identity between a query sequence and a reference sequence can be determined with the aid of a commercially available sequence comparison program. This typically involves aligning the two sequences using the default scoring matrix and default gap penalty, identifying the number of exact matches, and dividing the number of exact matches with the length of the reference sequence. Suitable computer programs useful for determining identity include, for example, BLAST (blast.ncbi.nlm.nih.gov).

[0154] In the various embodiments as set out herein when reference is made to a SEQ ID NO., sequences that have certain percentage sequence identity to the full-length sequence are also within the scope of the invention.

[0155] The 16S rDNA of the bacterial species listed in Table 4 with reference to the sequence identifier in Table 1 and which is used in the compositions and methods of the invention has at least 90% e.g. at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%, sequence identity to the corresponding reference 16S rDNA (i.e. SEQ IDs 1 to 11). In some embodiments, the threshold sequence identity is at least 94.5%. In one embodiment, said sequence identity is at least 95%. In one embodiment, said sequence identity is at least 97%. In one embodiment, said sequence identity is at least 98.7%.

[0156] In one aspect, the composition therefore comprises one, two or more bacterial species comprising a 16S rDNA sequence selected from SEQ ID. NO. 1 to 4 or comprising a 16S rDNA sequence having at least 80%, 85% or 90% e.g. at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%; e.g. 97% or 98.7% identity to a nucleic acid sequence selected from SEQ ID NOs. 1 to 11.

[0157] In some embodiments, the threshold sequence identity is 94.5%, 94.6%, 94.7%, 94.8%, 94.9%, 95.0%, 95.1%, 95.2%, 95.3%, 95.4%, 95.5%, 95.6%, 95.7%, 95.8%, 95.9%, 96.0%, 96.1%, 96.2%, 96.3%, 96.4%, 96.5%, 96.6%, 96.7%, 96.8%, 96.9%, 97.0%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98.0%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9% 99.0%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 100%. In one embodiment, a bacterium present in the composition belongs to the same species as a bacterium disclosed herein, has at least 90% e.g. at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%; e.g.

[0158] 97% or 98.7% identity to a nucleic acid sequence selected from SEQ ID NOs. 1 to 11 and retains activity against radiation enteritis.

[0159] In one example, species used in the composition are identified based on their 16S rDNA sequence (e.g., full-length sequence, or partial sequence). In some cases, strains of bacterial species useful in an invention, e.g., strains of the species disclosed herein, can be obtained from a public biological resource center such as the ATCC (atcc.org), the DSMZ (dsmz.de), or the Riken BioResource Center (en.brc.riken.jp). 16s rDNA sequences useful for identifying species or other aspects of the invention can be obtained from public databases, e.g., the Human Microbiome Project (HMP) web site or GenBank.

[0160] A skilled person would appreciate that the compositions may include one or more than one strain of a particular bacterial species as listed in Table 1. For example, the composition of the invention comprises more than one bacterial strain for species. For example, in some embodiments, the composition of the invention comprises more than one strain from within the same species listed in Table 1 (e.g. more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40 or 45 strains). In another embodiment, the composition of the invention comprises one bacterial strain for each species.

[0161] In one embodiment, the bacteria of the composition are capable of colonising the gastrointestinal tract of a subject. In one embodiment, the bacteria of the composition are capable of sustained engraftment in the gastrointestinal tract of a subject.

[0162] In one embodiment, the composition is used in methods of treating radiation enteritis and has one or more of the following characteristics which include biological and clinical characteristics:

[0163] • The composition is effective in treating and / or preventing radiation induced Gl toxicities, e.g.

[0164] radiation enteritis, such as acute or chronic radiation enteritis in a subject. Treatment of radiation enteritis reduces one or more symptoms of radiation enteritis;

[0165] • The composition is effective in treating and / or preventing radiation induced Gl toxicities, e.g.

[0166] radiation enteritis, in an in vitro or in vivo model for radiation enteritis. For example, the model may be an organoid model as in the examples;

[0167] • Administering the composition to a cell, tissue or subject modulates one or more biomarkers, such as ZO-1, claudin-1, occludin, claudin-5, desmocollin-2 and e-cadherin.

[0168] • Administering the composition to a cell, tissue or subject increases the abundance of bacteria in the subject which creates an environment or microenvironment (e.g., metabolome) that is conducive to the treatment of radiation induced Gl toxicities, e.g. radiation enteritis;

[0169] • Administering the composition to a cell, tissue or subject; e.g. in an in vitro or in vivo model, reduces or preventing disruption of, or increasing, barrier integrity of a human cell line (e.g. an epithelial cell) monolayer, e.g. a Caco2 cell monolayer treated with the consortium where the barrier function is measured by electrical impedance. This can be measured as shown in the examples.

[0170] Suitable assays are shown in the examples.

[0171] Thus, the composition includes at least one bacterial strain which shows one or more of the features set out above.

[0172] The ability of the specific bacteria or the combination of bacterial species to induce an anti-inflammatory effect e.g. as defined above can be assessed using any of method known in the art, e.g., in vitro assays for example using cell culture, or in vivo studies.

[0173] The subject may be a human or animal model, such a rodent, e.g. mouse model. A therapeutic composition and / or method is tested by administering the composition to the animal model either prior to induction of disease signs or symptoms, during induction, or after manifestation of at least one sign or symptom in the animal. In vitro or ex vivo models can also be used for testing efficacy, e.g. tissue or cell-based models.

[0174] The bacterial isolates can be isolated as described in WO2013 / 171515 or WO2017 / 182796, both incorporated by reference. In one embodiment, bacterial strains are cultured and grown individually and then combined in the composition.

[0175] A bacterial isolate used in the composition is preferably a non-pathogenic strain. In other words, the bacterium preferably does not cause a disease in a healthy human individual when administered to said individual.

[0176] In one embodiment, each bacterium present in the composition is susceptible to treatment with one or more antibiotics. In other words, the bacterium is not resistant to treatment with at least one antibiotic. This allows antibiotic treatment of an individual in the event that one or more of the bacteria included in a therapeutic composition administered to the individual cause disease in the individual, contrary to expectations. Thus, in one embodiment, the bacterium is susceptible to treatment with one or more antibiotics selected from the group consisting of: a beta-lactam, fusidic acid, elfamycin, aminoglycoside, fosfomycin, tunicamycin metronidazole and / or vancomycin. In vitro and in silico methods for screening bacteria for antibiotic resistance are known in the art.

[0177] In one embodiment, the isolated bacterium included in the compositions may not comprise one or more genes encoding one or more virulence factors and / or preferably does not produce one or more virulence factors. Virulence factors in this context are properties which enhance the potential of a bacterium to cause disease in an individual. Virulence factors include the production of bacterial toxins, such as endotoxins and exotoxins by a bacterium, as well as the production of hydrolytic enzymes that may contribute to the pathogenicity of the bacterium. Methods for screening bacteria for genes encoding virulence factors are known in the art.

[0178] In some embodiments, one or more of the bacterial strains are human-derived bacteria, meaning the one or more bacterial strains were obtained from or identified from a human or a sample therefrom (e.g., a human donor). In some embodiments of the compositions provided herein, all of the bacterial strains are human-derived bacteria. In some embodiments of the compositions provided herein, the bacterial strains are derived from more than one human donor.

[0179] Isolation and characterisation can be achieved using standard methods in the art. For example, the V4-V5 region of the 16S rRNA encoding gene can be amplified and sequenced. Sequences can then be aligned and compared to the 16S sequences provided herein for the bacterial isolates. Sequence protocols and alignment software are well known in the art.

[0180] In some cases, strains of bacterial species useful in an invention, e.g., strains of the species disclosed herein, can be obtained from a public biological resource centre as described above.

[0181] The bacterial strains used in the live bacterial products provided herein generally are isolated from the microbiome of healthy individuals. In some embodiments, the live bacterial products include strains originating from a single individual. In some embodiments, the live bacterial products include strains originating from multiple individuals. In some embodiments, the bacterial strains are obtained from multiple individuals, isolated and grown up individually. The bacterial compositions that are grown up individually may subsequently be combined to provide the compositions of the disclosure. It should be appreciated that the origin of the bacterial strains of the live bacterial products provided herein is not limited to the human microbiome from a healthy individual.

[0182] In some embodiments in which the composition of the invention comprises more than one bacterial strain, species or genera, the individual bacterial strains, species or genera may be for separate, simultaneous or sequential administration. In some embodiments, the more than one bacterial strain, species or genera are stored separately but are mixed together prior to use.

[0183] As explained herein, the bacterial compositions according to the various aspects of the invention have a therapeutic effect when administered to a subject and can be used in the treatment or prevention of radiation induced Gl toxicities, e.g. radiation enteritis. Thus, the compositions as described here are therapeutic compositions, i.e. pharmaceutical compositions. Excipients, administration regimen and methods for preparation of composition

[0184] In one embodiment, the composition may comprise a pharmaceutically acceptable excipient, carrier, buffer, stabilizer or other materials well known to those skilled in the art. Such materials should be nontoxic and should not interfere with the efficacy of the isolated bacteria present in the therapeutic composition. The precise nature of the pharmaceutically acceptable excipient or other material will depend on the route of administration, which may be oral or rectal. Many methods for the preparation of therapeutic compositions are known to those skilled in the art.

[0185] The bacterial compositions of the invention may comprise a prebiotic, a pharmaceutically acceptable carrier, insoluble fibre, a buffer, an osmotic agent, an anti-foaming agent and / or a preservative. Particular examples of excipients included in the composition are disclosed below.

[0186] Prebiotics may provide nutrients for the isolated bacteria present in the bacterial composition to assist their early growth and colonisation after administration to the individual. Any prebiotic known in the art may be used. Non-limiting examples of prebiotics include oligosaccharides, e.g., fructooligosaccharides such as oligofructose and inulin, mannan oligosaccharides and galactooligosaccharides, soluble oligofructose-enriched inulin and soluble fibre. Insoluble fibre may be included in the therapeutic composition as a carrier, e.g., to provide protection during transit or storage. A buffer may be included in the bacterial composition to promote the viability of the isolated bacteria present. An anti-fungal agent may be included in the bacterial composition as a preservative.

[0187] In one embodiment, the therapeutic bacterial compositions may comprise no other active ingredient other than the bacterial isolates as described herein, including no other isolated bacterium, and optionally a prebiotic. Thus, the active ingredient of the therapeutic composition may consist of the group of bacterial isolates as described herein, and optionally a prebiotic.

[0188] The bacterial compositions of the invention can be administered to a subject in a variety of ways as described in more detail elsewhere herein, including in the form of a capsule, tablet, gel or liquid.

[0189] The bacterial compositions of the invention may be for oral or rectal administration to the subject. Where the composition is for oral administration, the composition may be in the form of a capsule, or a tablet. Where the therapeutic composition is for rectal administration, the therapeutic composition may be in the form of an enema. The preparation of suitable capsules, tablets and enema is well-known in the art. The capsule or tablet may comprise an enteric coating to protect the capsule or tablet from stomach acid. For example, the capsule or tablet may be enteric-coated, pH dependant, slow-release, and / or gastro-resistant. Such capsules and tablets are used, for example, to minimize dissolution of the capsule or tablet in the stomach but allow dissolution in the small and / or large intestine. When intended for oral administration, the composition can be in solid or liquid form, where semi-solid, semi-liquid, suspension and gel forms are included within the forms considered herein as either solid or liquid.

[0190] As a solid composition for oral administration, the composition can be formulated into a powder, granule, compressed tablet, pill, capsule, chewing gum, wafer or the like. Such a solid composition typically contains one or more inert diluents. In addition, one or more of the following can be present: binders such as carboxymethylcellulose, ethyl cellulose, microcrystalline cellulose, or gelatin, excipients such as starch, lactose or dextrins, disintegrating agents such as alginic acid, sodium alginate, corn starch and the like; lubricants such as magnesium stearate, glidants such as colloidal silicon dioxide, sweetening agents such as sucrose or saccharin, a flavoring agent such as peppermint, methyl salicylate or orange flavoring; and a coloring agent. When the composition is in the form of a capsule (e. g. a gelatin capsule), it can contain, in addition to materials of the above type, a liquid carrier such as polyethylene glycol, cyclodextrin or a fatty oil.

[0191] When intended for oral administration, a composition can comprise one or more of a sweetening agent, preservatives, dye / colorant and flavor enhancer. In a composition for administration by injection, one or more of a surfactant, preservative, wetting agent, dispersing agent, suspending agent, buffer, stabilizer and isotonic agent can also be included.

[0192] The bacterial composition may include a pharmaceutically acceptable carrier or vehicle can be particulate, so that the compositions are, for example, in tablet or powder form. The term "carrier" refers to a diluent, adjuvant or excipient, with which the composition is administered. Such pharmaceutical carriers can be liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The carriers can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating and coloring agents can be used. In one embodiment, the composition and pharmaceutically acceptable carriers are sterile. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical carriers also include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents.

[0193] The compositions can take the form of one or more dosage units. In an embodiment, the dose unit comprises at least 1 x 103, 1 x 104, 1 x 105, 1 x106, 1 x107, 1 x 108, 1 x 109, 1 x1010, 1 x 1011, 1 x1012, 1 x1013or greater than 1 x1013colony forming units (cfu) of vegetative bacterial cells. In an embodiment, the dose unit comprises a pharmaceutically acceptable excipient, an enteric coating or a combination thereof. The bacterial isolates or composition may be provided at a dose of 0.1 - 100 g / day, such as 0.1, 0.5, 1, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80 or 90 g / day.

[0194] The isolated bacterium or isolated bacteria present in a therapeutic composition may make up at least 1 %, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, or 90% of the therapeutic composition by volume or weight.

[0195] Treatments or specific processes can be applied to improve the stability or viability of the bacterial isolates in the composition. The bacterial composition can be applied in a dry form or in a wet form. The bacterial composition may be lyophilized. The lyophilized therapeutic composition may comprise one or more stabilisers and / or cryoprotectants. The lyophilized bacterial composition may be reconstituted using a suitable diluent prior to administration to the individual.

[0196] In another aspect, there is provided a bacterial or pharmaceutical composition described herein for use in the treatment or prevention of Gl related toxicities, e.g. radiation enteritis. In another aspect, there is provided the use of a bacterial or pharmaceutical composition described herein in the manufacture of a medicament for the treatment or prevention of Gl related toxicities, e.g. radiation enteritis. The invention also relates to a method for treating or preventing radiation induced gastrointestinal toxicities, e.g. radiation enteritis, comprising administering a bacterial or pharmaceutical composition described herein.

[0197] As used herein, "treat", "treating" or "treatment" means inhibiting or relieving a disease or disorder. For example, treatment can include a postponement of development of the symptoms associated with a disease or disorder, and / or a reduction in the severity of such symptoms that will, or are expected, to develop with said disease. The terms include ameliorating existing symptoms, preventing additional symptoms, and ameliorating or preventing the underlying causes of such symptoms. Thus, the terms denote that a beneficial result is being conferred on at least some of the mammals, e.g., human patients, being treated. Many medical treatments are effective for some, but not all, patients that undergo the treatment.

[0198] The term "subject" or "patient" refers to an animal which is the object of treatment or prevention. By way of example only, a subject includes, but is not limited to, a mammal, including, but not limited to, a human or a non-human mammal, such as a non-human primate, murine, bovine, equine, canine, ovine, or feline.

[0199] In one embodiment, the disease treated or prevented is radiation enteritis and the composition provides a radiation enteritis therapy. The term “radiation enteritis therapy” refers to any therapeutic regimen that aims to reduce or eliminate radiation enteritis or symptoms of radiation enteritis or slow the progression of radiation enteritis. The anti radiation enteritis therapies described herein involve the administering anti Gl toxicities, e.g. radiation enteritis therapies to a subject, e.g., a subject having radiation enteritis or at risk of having radiation enteritis, e.g. a cancer patient. As explained elsewhere, the composition may be administered prior to, concurrent with or after radiation treatment in cancer therapy. For example, the composition may be administered 3, 2 or 1 month prior to radiation therapy, for example 1, 2 or 3 weeks prior. For example, the composition may be administered 3, 2 or 1 month after radiation therapy, for example 1, 2 or 3 weeks after. For example, administration may commence prior to radiation treatment and continue until after radiation treatment.

[0200] In one embodiment, the composition is used for prevention of Gl toxicities, e.g. radiation enteritis and is administered prior to radiation treatment.

[0201] As explained elsewhere, radiation enteritis is a toxic side effect of cancer therapy with radiation treatment. In one embodiment, the cancer to be treated may include but is not limited to the cancers listed above, including colorectal, gastric, oesophageal, anal, testicular, prostate, breast, ovarian, endometrial, cervical, bladder, pancreatic, liver, lung, skin, bone, head and neck, brain, thyroid, oral cancers, lymphomas, myelomas and sarcomas.

[0202] Administration according to the method and uses above includes oral administration or rectal administration.

[0203] The amount of the composition that is effective / active in the treatment of radiation enteritis will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays can optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each patient's circumstances. Factors like age, body weight, sex, diet, time of administration, rate of excretion, condition of the host, drug combinations, reaction sensitivities and severity of the disease shall be taken into account.

[0204] In some embodiments, a composition of the invention may be administered with two or more (e.g., 2, 3, 4, 5, or more) therapeutic agents, e.g. agents or therapies useful in the treatment of radiation enteritis and / or cancer.

[0205] As explained elsewhere, the subject may have received, is receiving or will receive radiation therapy. Further, the subject may also have received, is receiving or will receive other anti-cancer therapies. Agents useful in the treatment of cancer may be selected from small molecules, or antibodies. Such therapies are set out below. In one embodiment, the cancer treatment may be provided before or after surgery.

[0206] Immune checkpoints are regulatory pathways within the immune system that are involved in maintaining immune homeostasis (e.g., self-tolerance, modulating the duration and extent of an immune response) to minimize cellular damage due to aberrant immune responses. Inhibitors of immune checkpoints, herein referred to as “immune checkpoint inhibitors,” specifically inhibit immune checkpoints and may have a stimulatory or inhibitory effect on the immune response.

[0207] In one embodiment, the immune checkpoint inhibitor is an antibody or fragment thereof, an interfering nucleic acid molecule or another chemical entity.

[0208] A number of checkpoint inhibitors are known in the art and a number of treatments have been approved by regulatory authorities, including antibody treatments, whilst others, including treatments with monoclonal antibodies or antibody fragments, such as single domain antibodies, have shown efficacy across a wide range of cancers.

[0209] In one embodiment, the immune checkpoint inhibitor inhibits PD-1 activity, i.e. acts as PD-1 antagonist.

[0210] " PD-1 antagonist" or “PD-1 inhibitor” means any chemical compound or biological molecule that blocks binding of PD-L1 expressed on a cancer and or immune cell to PD-1 expressed on an immune cell (T cell, B cell or NKT cell) and preferably also blocks binding of PD-L2 expressed on a cancer and or immune cell to the immune-cell expressed PD-1.

[0211] In one embodiment, the immune checkpoint inhibitor is a PD-1 inhibitor, PD-L1 inhibitor or PD-L2 inhibitor, e.g. an anti PD-1 antibody or anti PD-L1 or anti PD-L2 antibody. In one embodiment, the immune checkpoint inhibitor is an anti PD-1 antibody. In one embodiment, the immune checkpoint inhibitor is an anti PD-1 or PD-L1 antibody optionally selected from nivolumab (MDX- 1106, MDX-1106-04, ONO-4538, or BMS-936558), pembrolizumab (Trade name KEYTRUDA® formerly Lambrolizumab®, also known as Merck 3745, MK-3475 or SCH-900475), cemiplimab, avelumab, durvalumab, atezolizumab, spartalizumab, camrelizumab, sintilimab, tislelizumab, pidilizumab or toripalimab.

[0212] In one embodiment, the immune checkpoint inhibitor is an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4 inhibitor), i.e. inhibits the activity of CTLA-4. CTLA-4 (CD152) is a B7 / CD28 family member that inhibits T cell functions with NCBI Gene ID: 1493. CTLA-4 mAbs or CTLA-4 ligands can prevent CTLA-4 from binding to its native ligands, thereby blocking the transduction of the T-cell negative regulating signal by CTLA-4 and enhancing the responsiveness of T-cells to various antigens. In this aspect, results from in vivo and in vitro studies are substantially in concert. The CTLA4 inhibitor can be a CTLA4 antibody, optionally Ipilimumab or Tremelimumab.

[0213] In one embodiment, the immune checkpoint inhibitor is an anti-TGIT, anti-LAG3 or anti-TIM3 agent, e.g. an antibody. The checkpoint targets listed herein are not limiting and a skilled person would understand that other checkpoint targets are also within the scope of the invention and may be inhibited.

[0214] It should further be appreciated that multiple immune checkpoint inhibitors may be used in the methods, compositions, and kits disclosed herein.

[0215] In some embodiments, the cancer immunotherapy agent comprises an anticancer vaccine (also referred to herein as a cancer vaccine). Cancer vaccines generally act to increase an immune response to cancer cells. For example, cancer vaccines include cancer antigen(s) that act to induce or stimulate an immune response against cells bearing the cancer antigen(s). The immune response induced or stimulated can include an antibody (humoral) immune response and / or a T-cell (cell-mediated) immune response.

[0216] Unless otherwise specified, the term PD-1 as used herein refers to human PD-1. The terms " Programmed Death 1", " Programmed Cell Death 1", " Protein PD-1", " PD-1", PD1", " PDCD1", "hPD-1" and "hPD-1" are used interchangeably, and include variants, isoforms, species homologs of human PD-1. The term PD-1 antibody or antibody fragment refers to a molecule capable of specifically binding to the human PD-1 antigen and antagonising PD-1 action. Human PD-1 amino acid sequences can be found in NCBI Locus No.: NP_005009. Human PD-L1 and PD-L2 amino acid sequences can be found in NCBI Locus No.: NP_054862 and NP_079515, respectively.

[0217] The term "antibody" as used herein broadly refers to any immunoglobulin (Ig) molecule, or antigen binding portion thereof, comprised of four polypeptide chains, two heavy (H) chains and two light (L) chains, or any functional fragment, mutant, variant, or derivation thereof, which retains the essential epitope binding features of an Ig molecule. Such mutant, variant, or derivative antibody formats are known in the art. The antibody may be mono or multispecific, e.g. bispecific. The antibody may be administered in combination with another antibody therapy, e.g. another antibody that targets a checkpoint inhibitor or in combination with another anti-cancer therapy.

[0218] In a full-length antibody, each heavy chain is comprised of a heavy chain variable region or domain (abbreviated herein as HCVR) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. Each light chain is comprised of a light chain variable region or domain (abbreviated herein as LCVR) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The heavy chain and light chain variable regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each heavy chain and light chain variable region is composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[0219] Immunoglobulin molecules can be of any type (e.g., IgG, IgE, IgM, IgD, IgA and IgY), class (e.g., IgG 1, lgG2, IgG 3, lgG4, IgAI and lgA2) or subclass.

[0220] The term antibody as used herein includes antibody fragments, such as F(ab')2, Fab, Fv, scFv, a heavy chain only antibody, single domain antibodies (VH, VL, VHH) or an antibody mimetic protein. Various antibody formats have been shown to show efficacy against checkpoint inhibitors, including single domain antibodies (e.g. Yu S et al. Nanobodies targeting immune checkpoint molecules for tumor immunotherapy and immunoimaging, Int J Mol Med. 2021;47(2):444-454).

[0221] scFv fragments (~25kDa) consist of the two variable domains, VH and VL. Naturally, VH and VL domain are non-covalently associated via hydrophobic interaction and tend to dissociate. However, stable fragments can be engineered by linking the domains with a hydrophilic flexible linker to create a single chain Fv (scFv). The smallest antigen binding fragment is the single variable fragment, namely the VH or VL domain. Binding to a light chain / heavy chain partner respectively is not required for target binding. Such fragments are used in single domain antibodies. A single domain antibody (~12 to 15 kDa) therefore has either the VH or VL domain.

[0222] The antibody may be human, humanised or chimeric. A chimeric antibody is a recombinant protein that contains the variable domains including the complementarity determining regions (CDRs) of an antibody derived from one species, preferably a rodent antibody, while the constant domains of the antibody molecule are derived from those of a human antibody.

[0223] A humanized antibody is a recombinant protein in which the CDRs from an antibody from one species; e.g., a rodent antibody, are transferred from the heavy and light variable chains of the rodent antibody into human heavy and light variable domains (e.g., framework region sequences). The constant domains of the antibody molecule are derived from those of a human antibody. In certain embodiments, a limited number of framework region amino acid residues from the parent (rodent) antibody may be substituted into the human antibody framework region sequences.

[0224] Checkpoint inhibitors are not limited to antibodies. In one embodiment, the immune checkpoint inhibitor is an interfering nucleic acid molecule, optionally wherein the interfering nucleic acid molecule is an siRNA molecule, an shRNA molecule or an antisense RNA molecule. In one embodiment, the immune checkpoint inhibitor is a small molecule or PROteolysis TArgeting Chimera (PROTAC), alternative scaffold protein, biologies or other immune checkpoint inhibitors. In one embodiment, the immune checkpoint inhibitor is an interfering nucleic acid molecule. In one embodiment, the interfering nucleic acid molecule is an siRNA molecule, an shRNA molecule or an antisense RNA molecule. In one embodiment, the immune checkpoint inhibitor is a small molecule or a PROteolysis TArgeting Chimera (PROTAC) or other immune checkpoint inhibitors. Examples that small molecules can be used as checkpoint inhibitors is provided by research on sulfamonomethoxine and sulfamethizole. Exemplary small molecule compounds that inhibit PD-L1 are disclosed in US9850225 incorporated herein by reference. A small molecule currently in human clinical trials is a molecule called Ca-170, which inhibits both the PD-L1 pathway and the V-domain Ig suppressor of the T-cell activation (VISTA) pathway.

[0225] In one embodiment, the immune checkpoint inhibitor is a peptide inhibitor. An example is the peptide antagonist, (D)PPA-1, which blocks the PD-1 / PD-L1 interaction and decreases tumor growth in vivo (Chang H. N et al, Blocking of the PD-1 / PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy. Angew. Chem. Int. Ed. 2015;54:11760-11764). Another peptide inhibitor is PL120131, shown to act as a competitive inhibitor of PD-L1 (Magiera-Mularz K. et al Bioactive Macrocyclic Inhibitors of the PD-1 / PD-L1 Immune Checkpoint. Angew. Chem. Int. Ed. 2017;56:13732-13735) and TPP-1 (Li C., Zhang N et al, Peptide Blocking of PD-1 / PD-L1 Interaction for Cancer Immunotherapy. Cancer Immunol. Res. 2018;6:178-188).

[0226] The anti-cancer therapy used additionally to radiation therapy may include a therapeutic agent and includes gene therapy, viral therapy, RNA therapy bone marrow transplantation, nanotherapy, targeted anti-cancer therapies ora combination thereof. Examples of other therapeutic agents include checkpoint inhibitors, antineoplastic agents, immunogenic agents, attenuated cancerous cells, tumour antigens, antigen presenting cells such as dendritic cells pulsed with tumour-derived antigen or nucleic acids, immune stimulating cytokines (e.g., IL-2, IFNa2, GM-CSF), targeted small molecules and biological molecules (such as components of signal transduction pathways, e.g. modulators of tyrosine kinases and inhibitors of receptor tyrosine kinases, and agents that bind to tumour- specific antigens, including EGFR antagonists), an anti-inflammatory agent, or an immunosuppressive agent and cells transfected with a gene encoding an immune stimulating cytokine (e.g., GM-CSF). In one embodiment, subject may have received, is receiving or will receive surgery. In one embodiment, the composition is used in combination with a stem-cell transplant therapy comprising a peripheral blood transplant, a bone marrow transplant, a cord blood transplant, or a skin-derived stem cell transplant.

[0227] In one embodiment, the subject may have received, is receiving or will receive adoptive cell transfer (ACT). In general, adoptive cell transfer therapy involves harvesting cells from a subject, specifically producing or expanding a specific cell population, optionally activating the cells, and administering the expanded cells to the subject. In some embodiments, the desired cells are immune cells capable of killing or eliminating cancer cells.

[0228] In some embodiments, the adoptive cell transfer therapy uses engineered T-cell receptors or chimeric antigen receptors, which may be referred to as CAR-T therapy. CAR-T cells include T-cells taken from a subject that are genetically engineered to express chimeric antigen receptors (CARs) on the cell surface. The CAR-T cell receptors are designed to recognize a specific antigen on cancer cells (e.g., a cancer antigen). After the CAR-T cells are infused into the subject, the CAR-T cells recognize and kill cancer cells that express the specific antigen on their surfaces. In some embodiments, the CAR-T cells are autologous cells, meaning the T cells were harvested and re-administered to the same subject. In some embodiments, the CAR-T cells are CD8+ T cells. In some embodiments, the CAR-T cells are allogeneic cells, meaning the T cells were harvested from one subject (e.g., the donor) and administered to a different subject (e.g., the recipient).

[0229] Examples of cancer antigens that may be targeted by CAR-T cells are known in the art, and selection of a cancer antigen for targeting will depend on factors such as the cancerthat is being targeted.

[0230] In some embodiments, the anticancer therapy involves administering one or more costimulatory agents. In some embodiments, the costimulatory agent is a molecule that targets one or more costimulatory molecules, thereby modulating the immune response. In some embodiments, the costimulatory agent enhances an anticancer immune response, for example, by preventing the downregulation of an immune response. A costimulatory agent may be administered alone in a cancer therapy or in combination with one or more cancer therapies to enhance the therapeutic effect of the cancer therapy. In some embodiments, the costimulatory agent is an antibody that targets CD-28, OX-40, 4-1 BB, or CD40. In some embodiments, the subject may have received, is receiving or will receive therapy with two or more (e.g., 2, 3, 4, 5, or more) therapeutic agents.

[0231] In one embodiment, subject may have received, is receiving or will receive therapy with an agent involved in T-cell activation, a tumour microenvironment modifier (TME) or a tumour-specific target.

[0232] In one embodiment, the method and uses further comprise administering an antibiotic to the subject.

[0233] In some embodiments, the individual has cancer that is resistant (has been demonstrated to be resistant) to one or more anti-cancer therapies. In some embodiments, resistance to anti-cancer therapy includes recurrence of cancer or refractory cancer. Recurrence may refer to the reappearance of cancer, in the original site ora new site, after treatment. In some embodiments, resistance to anti-cancer therapy includes progression ofthe cancerduring treatment with the anti-cancer therapy. In some embodiments, the cancer is at early stage or at late stage.

[0234] Administration may be in a "therapeutically effective amount", this being sufficient to show benefit to the individual. Such benefit may be at least amelioration of at least one symptom. Thus “treatment” of a specified disease refers to amelioration of at least one symptom. The actual amount administered, and rate and time-course of administration, will depend on the nature and severity of what is being treated, the particular patient being treated, the clinical condition of the individual patient, the site of delivery of the composition, the type of therapeutic composition, the method of administration, the scheduling of administration and other factors known to medical practitioners. Prescription of treatment, e.g. decisions on dosage etc., is within the responsibility of general practitioners and other medical doctors, and may depend on the severity of the symptoms and / or progression of a disease being treated. A therapeutically effective amount or suitable dose of a therapeutic composition of the invention can be determined by comparing its in vitro activity and in vivo activity in an animal model. Methods for extrapolation of effective dosages in mice and other test animals to humans are known. The precise dose will depend upon a number of factors, including whether the therapeutic composition is for prevention or for treatment.

[0235] In one embodiment of the methods which require administration of the composition, the method includes the further step of detecting the presence one or more of the bacterial strains that have been administered in the subject subsequent to administration. Methods for detection include for example detecting a nucleic acid sequence of the bacterial isolate in said subject, e.g. using PCR.

[0236] Efficacy of a treatment can be determined by evaluating signs and or symptoms and according to whether induction of improvement and / or maintenance of a remission or improved condition is achieved, e.g., for at least 1 week, at least two weeks, at least three weeks, at least four weeks, at least 8 weeks, or at least 12 weeks. For example, mucosal healing as judged endoscopically, histologically or via imaging techniques can be used for such evaluations, particularly for predicting long term clinical outcome in subject's diagnosed with radiation enteritis.

[0237] In one embodiment, the term “clinical response” as used herein as it relates to a subject’s response to drug administration and, for cancer treatment, can be determined by assessing tumor growth / remission

[0238] In one embodiment of the methods which require administration of the composition, the method includes the further step of detecting the presence of one or more bacterial strain that has been administered in the subject subsequent to administration. Methods for detection include for example detecting a nucleic acid sequence of the bacterial isolate in said subject. The composition for use as described herein may be prepared by a method comprising culturing the one, two or more isolated bacteria present in the composition in a suitable medium or media. Bacteria may be co-cultured. Media and conditions suitable for culturing the bacteria to be included in the therapeutic composition of the present invention are described in detail elsewhere herein. For example, a method of preparing a therapeutic composition according to the present invention may comprise the steps of:

[0239] (i) culturing a first isolated bacterium;

[0240] (ii) culturing a second and optionally a further isolated bacterium; and

[0241] (iii) mixing the bacteria obtained in (i) and (ii) to prepare the therapeutic composition.

[0242] The isolated bacteria to be included in the composition may be cultured in separate steps. In other words, a separate culture of each bacterium to be included in the therapeutic composition is preferably prepared. This allows the growth of each bacterium to be evaluated and the amount of each bacterium to be included in the pharmaceutical composition to be controlled as desired. The bacteria cultured in steps (i) and (ii) preferably have distinct 16S nucleic acid sequences, that is 16S nucleic acid sequences that share less than 99%, 98.7%, 98%, 97%, 96% or 95% sequence identity.

[0243] The above method may include steps of culturing each isolated bacterium which is to be included in the composition.

[0244] The method may optionally comprise one or more further steps in which the bacteria are mixed with one or more additional ingredients, such as a pharmaceutically acceptable excipient, prebiotic, carrier, insoluble fibre, buffer, osmotic agent, antifoaming agent, and / or preservative. In addition, or alternatively, the method may comprise suspending the bacteria obtained in (i) and optionally (ii) in a chemostat medium, or saline, e.g. 0.9% saline. The bacteria obtained in (i) and optionally (ii) may be provided under a reduced atmosphere, such as N2, CO2, H2, or a mixture thereof, e.g. N2: CO2: H2. The gases may be present in appropriate ratios for the preservation of the bacteria present in the therapeutic composition. For example, the reduced atmosphere may comprise 80% N2, 10% CO2 and 10% H2. In addition, or alternatively, the method may comprise a step of lyophilising the bacteria obtained in (i) and optionally (ii), optionally in the presence of a stabiliser and / or cryprotectant. The method may also comprise a step of preparing a capsule, tablet, or enema comprising the bacteria obtained in (i) and optionally (ii). The capsule or tablet may be enteric-coated, pH dependant, slow-release, and / or gastro-resistant.

[0245] The composition for use as described herein may also be provided in the form of a food supplement, beverage or other food stuff. The invention thus also relates to a food product comprising the composition of the invention. In one embodiment, the bacteria can be viable bacteria that are capable of colonising and / or engraftment of the gastrointestinal gut of a subject when administered to said subject.

[0246] In another aspect, the invention relates to a method for augmenting FMT therapy for treating radiation enteritis with one or more bacterial isolate from one or more family, genus or species as disclosed herein. Thus, in one embodiment, the method comprises the step of adding the one or more bacterial isolate from one or more species as disclosed herein to an FMT sample.

[0247] Excipients in the composition, dosage forms of the composition and administration routes may be selected from those explained above.

[0248] Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. While the foregoing disclosure provides a general description of the subject matter encompassed within the scope of the present invention, including methods, as well as the best mode thereof, of making and using this invention, the following examples are provided to further enable those skilled in the art to practice this invention and to provide a complete written description thereof. However, those skilled in the artwill appreciate that the specifics of these examples should not be read as limiting on the invention, the scope of which should be apprehended from the claims and equivalents thereof appended to this disclosure. Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure.

[0249] All documents mentioned in this specification are incorporated herein by reference in their entirety, including any references to gene accession numbers and references to patent publications.

[0250] "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, " A and / or B" is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein. Unless context dictates otherwise, the descriptions and definitions of the features set out above are not limited to any particular aspect or embodiment of the invention and apply equally to all aspects and embodiments which are described.

[0251] The invention further relates to the following embodiments.

[0252] 1. A composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae for use in the treatment or prevention of radiation induced gastrointestinal toxicities.

[0253] 2. The composition of embodiment 1 wherein the composition is for use in the treatment or prevention of radiation enteritis. 3. The composition of embodiment 1 or 2 comprising isolated bacteria belonging to the family Coriobacteriaceae and Christensenellaceae.

[0254] 4. The composition of any preceding embodiment comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and Barnesiellaceae.

[0255] 5. The composition of embodiment 1 or 2 comprising isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and / or Barnesiella.

[0256] 6. The composition of embodiment 3 comprising isolated bacteria belonging to the genus Senegalimassilia and Christensenella.

[0257] 7. The composition of embodiment 4 comprising isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and Barnesiella.

[0258] 8. The composition of embodiment 1 or 5 comprising isolated bacteria selected from Christensenellaceae sp., Senegalimassilia anaerobia, Prevotella copri and / or Barnesiella intestinihominis.

[0259] 9. The composition of embodiment 3 or 6 comprising isolated bacteria selected from Christensenellaceae sp. and Senegalimassilia anaerobia.

[0260] 10. The composition of embodiment 4 or 7 comprising isolated bacteria selected from Christensenellaceae sp., Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis.

[0261] 11. The composition of embodiment 1 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5 isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and / or isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

[0262] 12. The composition of embodiment 3 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7.

[0263] 13. The composition of embodiment 4 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28. 14. The composition according to a preceding embodiment comprising one or more further bacteria.

[0264] 15. The composition according to embodiment 14, wherein the further bacteria belong to the family Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae, Ruminococcaceae and / or Lachnospiraceae. 16. The composition according to embodiment 14 wherein the further bacteria belong to the genus Bifidobacterium, Eubacterium, Bacteroides, Ruminococcus and / or Roseburia

[0265] 17. The composition according to embodiment 14, wherein the further bacteria are selected from Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Eubacterium ventriosum, Bacteroides stercoris and / or Roseburia faecis bacteria.

[0266] 18. The composition according to embodiment 14, wherein the further bacteria comprise Slackia isoflavoniconvertens.

[0267] 19. The composition according to embodiments 14 to 18, wherein the one or more further bacteria are selected from Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae and / or Lachnospiraceae bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence selected from according to SEQ ID NO: 12 to 23.

[0268] 20. The composition according to embodiment 19 further comprising Slackia isoflavoniconvertens bacteria comprising a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 24 or 25.

[0269] 21. The composition according to any preceding embodiment, wherein said composition is formulated for oral or rectal administration.

[0270] 22. The composition according to embodiment 21, wherein said composition is in the form of a capsule, tablet, gel or liquid.

[0271] 23. The composition according to embodiment 22, wherein said composition is encapsulated in an enteric coating.

[0272] 24. The composition according to any preceding embodiment, wherein the composition comprises live, attenuated or killed bacteria.

[0273] 25. The composition according to any preceding embodiment, wherein the composition comprises bacterial spores.

[0274] 26. The composition according to any of embodiments 1 to 24, wherein the composition is substantially free of bacterial spores.

[0275] 27. The composition according to any preceding embodiment, wherein the composition comprises bacterial strains that originate from one or more human donor.

[0276] 28. The composition according to any preceding embodiment, wherein the bacteria are lyophilized.

[0277] 29. The composition according to any preceding embodiment, wherein the composition comprises at least about 1x103to 1x1013CFU of bacteria.

[0278] 30. The composition according to a preceding embodiment, wherein the composition is administered prior to, concurrent with or after radiotherapy treatment. 31. A method for treating radiation induced Gl toxicities, e.g. radiation enteritis comprising administering a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae to a subject.

[0279] 32. The method according to embodiment 31 comprising administering isolated bacteria belonging to the family Coriobacteriaceae and Christensenellaceae.

[0280] 33. The method of embodiment 31 or 32 comprising administering isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and Barnesiellaceae.

[0281] 34. The method of embodiment 31 comprising administering isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and / or Barnesiella.

[0282] 35. The method of embodiment 32 comprising administering isolated bacteria belonging to the genus Senegalimassilia and Christensenella.

[0283] 36. The method of embodiment 33 comprising administering isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and Barnesiella.

[0284] 37. The method of embodiment 31 or 32 comprising administering isolated bacteria selected from Christensenellaceae sp., Senegalimassilia anaerobia, Prevotella copri and / or Barnesiella intestinihominis.

[0285] 38. The method of embodiment 32 or 35 comprising administering isolated bacteria selected from Christensenellaceae sp. and Senegalimassilia anaerobia.

[0286] 39. The method of embodiment 33 or 36 comprising administering isolated bacteria selected from Christensenellaceae sp., Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis.

[0287] 40. The method of embodiment 31 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and / or isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

[0288] 41. The method of embodiment 32 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7.

[0289] 42. The method of embodiment 33 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2, 6 or 7 isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

[0290] 43. The method according to any of embodiments 31 to 42 comprising administering one or more further bacteria.

[0291] 44. The method according to embodiment 43, wherein the further bacteria belong to the family Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae, Ruminococcaceae and / or Lachnospiraceae. 45. The method according to embodiment 43 wherein the further bacteria belong to the genus Bifidobacterium, Eubacterium, Bacteroides, Ruminococcus and / or Roseburia.

[0292] 46. The method according to embodiment 43 wherein the further bacteria are Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Eubacterium ventriosum, Bacteroides stercoris and / or Roseburia faecis bacteria.

[0293] 47. The method according to embodiment 43 wherein the further bacteria comprise Slackia isoflavoniconverten.

[0294] 48. The method according to any of embodiments 43 to 47, wherein the one or more further bacteria are selected from Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae and / or Lachnospiraceae bacteria wherein the bacteria comprise a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NO: 12 to 23.

[0295] 49. The method according to embodiment 48 further comprising administering Slackia isoflavoniconverten bacteria comprising a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 24 or 25.

[0296] 50. The method according to any of embodiments 31 to 48, wherein said composition is formulated for oral or rectal administration.

[0297] 51. The method according to embodiment 50, wherein said composition is in the form of a capsule, tablet, gel or liquid.

[0298] 52. The method according to embodiment 51, wherein said composition is encapsulated in an enteric coating.

[0299] 53. The method according to any of embodiments 31 to 52, wherein the composition comprises live, attenuated or killed bacteria.

[0300] 54. The method according to any of embodiments 31 to 52, wherein the composition comprises bacterial spores.

[0301] 55. The method according to any of embodiments 31 to 52, wherein the composition is substantially free of bacterial spores.

[0302] 56. The method according to any of embodiments 31 to 55, wherein the composition comprises bacterial strains that originate from one or more human donor.

[0303] 57. The method according to any of embodiments 31 to 56, wherein the bacteria are lyophilized.

[0304] 58. The administering according to any of embodiments 31 to 57, wherein the composition comprises at least about 1x103to 1x1013CFU of bacteria. 59. The method according to of embodiments 31 to 58, wherein the composition is administered prior to, concurrent with or after radiotherapy treatment.

[0305] The invention is further described in the non-limiting examples.

[0306] Examples

[0307] Bacterial composition protects epithelial barrier and prohibit macrophage activation in epithelial cells

[0308] The function of gut epithelia as a physical barrier, fending off bacterial invasion, is also important in maintaining immune tolerance and prohibiting activation of immune cells. In order to verify this function, an in vitro model of epithelial / macrophage crosstalk was set up. In this model, Caco-2 epithelial cells were cocultured with human monocyte-derived macrophages in a transwell system, where any breach or cytokine production by the epithelial monolayer will influence the macrophages, present in the lower chamber of the transwell system. Indeed, the treatment of the Caco2 cell monolayer with Salmonella typhimurium, known to disrupt the epithelial barrier, allowed the translocation of heat-killed bacteria and the subsequent activation of macrophages that is demonstrated by the production of the inflammatory cytokines IL-1β, IL-6 and TNF-a. Interestingly, exposing the epithelial monolayer to the bacterial composition protected the barrier integrity, and therefore impairing heat-killed bacterial translocation, which is reflected by limited production of inflammatory cytokines by macrophages, which was even lower than untreated control (Figure 1). This clearly demonstrates that the barrier protective properties of the bacteria tested also protect against immune activation, resulting from bacterial translocation, which is a common underlying mechanism in a wide variety of diseases. The bacterial composition tested is shown in Table 2.

[0309] Bacterial consortium repairs dextran sodium sulphate (DSS)-induced epithelial permeability in colonic epithelial organoid lines

[0310] Organoids are miniature, three-dimensional models of human organs that are derived from human stem cell progenitors and can replicate many of the complex, multicellular structures and functions of actual organs. Owed to their nature that closely mimics the structure and function of real organs they provide a unique tool to study human disease, that surpasses animal models in certain aspects. Therefore, human colonic organoids were employed herein to study gut epithelial permeability and to create a human radiation enteritis disease model.

[0311] Increased epithelial barrier permeability contributes to the pathology of a number of diseases [9], An in vitro model of epithelial permeability was set up, using colonic epithelial organoid lines. In a two- dimensional setting, the barrier functions of these organoids were compromised by treatment with DSS, a widely used chemical for the induction of colitis in experimental models, and barrier permeability was determined by measuring the translocation of fluorescein isothiocyanate (FITC)-labelled dextran. Whereas DSS induced high levels of dextran translocation, treating the epithelial cells with the microbial composition markedly inhibited this translocation (Figure 2). This implies that the bacterial composition promotes epithelial barrier integrity and functionality. The bacterial composition tested is shown in Table 2.

[0312] Bacterial composition promotes cell adhesion protein expression in radiation enteritis organoid model

[0313] Radiation exposure impairs gut barrier function primarily through affecting the expression of tight junction proteins. The epithelial-protective properties of bacterial composition were verified in an in vitro model of radiation enteritis. In this model, human colon-derived organoids are exposed to radiation, following the microinjection of the bacterial composition inside these organoids. The ensuing real-time PCR analysis revealed that the microbial composition restored the radiation-depleted expression of some tight junction proteins, such as occludin and claudin-5. Furthermore, the bacterial composition boosted the expression of other tight junction proteins, like zonula occludens-1 (ZO-1) and claudin-1, in comparison to the irradiated control. This was also the case for the desmosomes component desmocollin-2 (DSC2) and the adherens junction molecule e-cadherin (E-CAD) (Figure 3). This indicates that the bacterial composition can protect the barrier functions of the gut epithelia from the harmful effects of radiation. The bacterial composition tested is shown in Table 2.

[0314] Bacterial composition promotes organoid regeneration and stem cell activity in radiation enteritis organoid model

[0315] Radiation exposure affects not only gut barrier function, but also the activity of stem cells within the barrier, which in turn impacts cellular regeneration and renewal. The ability of bacterial composition to protect the sternness and regeneration capacity of the epithelial barrier from the effects of radiation was determined in human colon-derived organoids. These organoids were exposed to radiation, following the microinjection of the bacterial composition inside them. The phenotype of the organoids was determined by microscopy, 48 hours post radiation. Pre-treatment with the microbial composition promoted the sternness of the epithelial barrier as reflected by a significantly higher proportion of mature organoids and significantly lower proportion of cystic organoids, when compared to the irradiated control (Figure 4A). This indicates that the microbial composition prompted the maturation cycle in organoids, leading to faster recovery of fully functional epithelium. Furthermore, real-time PCR analysis revealed that the microbial composition significantly increased the expression of the stem cell marker LGR5, when compared to irradiated organoids (Figure 4B). Overall, this indicates that the microbial composition promotes stem cell activity, following irradiation, leading to a prompt recovery of a mature functional epithelial barrier. The bacterial composition tested is shown in Table 2.

[0316] Different combinations of the strains of the bacterial composition promote cell adhesion protein expression in radiation enteritis organoid model

[0317] The four-strain bacterial composition promotes gut barrier function by inducing the expression of tight junction proteins in an in vitro model of radiation enteritis. Alternative compositions made from 2 or 3 strain mixtures of the individual strains of the bacterial composition were tested in the same model to determine their ability to modulate tight junction gene expression. The ensuing real-time PCR analysis revealed that several of the alternative microbial compositions promoted the expression of some tight junction proteins, such as occludin, ZO-1 and claudins, in comparison to the irradiated control. This was also the case for DSC2 and E-CAD (Figure 5). This indicates that several combinations of the bacterial composition, in particularthe 3-strain mixtures, can protect the barrier functions of the gut epithelia from the harmful effects of radiation. The bacterial compositions tested are shown in Table 3.

[0318] Conclusions

[0319] The herewith presented data is strong evidence that the described bacterial consortium can protect gut epithelial barrier from the damaging effects of ionizing radiation, by not only promoting the expression of tight junction proteins, central to barrier function, but also boosting stem cell activity within this barrier in response to radiation. These observations were generated in a human colonic organoid model, which is the best physiological representative of the human gut. In this model, human colon-derived organoids are exposed to radiation. These protective qualities are also reflected in the barrier functionality, as the bacterial consortium prevents inflammation-induced barrier leakiness. By ameliorating the gastrointestinal toxicities of radiotherapy, this bacterial composition can enhance patient tolerance to radiotherapy and following through the entire planned radiation regimen. The described bacterial consortium has a strong potential to protect against and treat radiation-induced enteritis.

[0320] Methods

[0321] Table 2 Bacterial composition

[0322] The bacteria were identified through metagenomic sequencing and bioinformatic analysis as described in W02022 / 069907. No Taxonomy SEQ ID NO for 16S sequence

[0323] used in all experiments herein

[0324] B1 Senegalimassilia anaerobia 1

[0325] B2 Christensenellaceae R-7 group sp. 2

[0326] B3 Prevotella copri 3

[0327] B4 Barnesiella intestinihominis 4

[0328]

[0329] Table 2

[0330] Bacterial combinations

[0331] Table 3

[0332] Bacterial

[0333] species S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S11 Barnesiella

[0334] intestinihom

[0335] inis X x X X x x X Senegalima

[0336] ssilia

[0337] anaerobia X X X X X X X Prevotella

[0338] copri X x X x X x X Christensen

[0339] ellaceae R-7

[0340]

[0341] group sp. x x X x X x X

[0342] Bacterial combination as tested in Figure 5 are shown in Table 3 above. Fields in grey (marked with x) designate bacteria present in the combination tested.

[0343] Bacterial growth

[0344] All bacterial work was carried out under anaerobic conditions. Media, reagents and plastics needed for bacterial work were transferred to the anaerobic cabinet at least 16h prior usage to allow oxygen reduction.

[0345] Bacteria were grown in Yeast Casitone Fatty Acids (YCFA) medium or Microbiotica Anaerobe Medium acetate (MABa) till they reached late log / early stationary phase. For macrophage assay, bacteria were centrifuged for 10 minutes at 3900 xg and resuspended in reduced complete Roswell Park Memorial Institute (cRPMI, Gibco) supplemented with 10% foetal bovine serum (FBS, Gibco), 20mM N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid (Hepes, Gibco), adjusting the concentration to 2x108CFU / ml. Bacterial composition was prepared by mixing equal volumes of each individual component. For organoid microinjection, bacterial composition was prepared by mixing 1x109CFU of each individual component and then the mixture was centrifuged for 10 minutes at 3900 xg and resuspended in 250ml of reduced Phenol Red (Sigma), diluted 1:1 with reduced Dulbecco's Phosphate Buffered Saline (DPBS, Gibco). For the preparation of Heat-killed Salmonella typhimurium (HK ST), bacterial culture was incubated at 95°C for 20 minutes, centrifuged for 10 minutes at 3900 xg and resuspended in cRPMI adjusting for a concentration of 2x108CFU / ml.

[0346] Macrophage activation assay

[0347] Caco-2 cells (ATCC) were routinely grown in Dulbecco's Modified Eagle Medium (DMEM, Gibco) supplemented with 20% FBS and non-essential amino acids (NEAA, Gibco), 37°C, 5% CO2. Cells were seeded onto collagen-coated transwells (24-well plates, PES, 0.4mm, Sigma), 1x105cells / well in 200ml media and 750ml media was added to the bottom chamber of the transwell. Twenty-four hours after seeding, growth media was removed from both chambers and replaced with Differentiation Medium supplemented with Mito+ (Intestinal Differentiation media Pack, Corning) and cells were incubated for 48h. Supernatant was then removed, plates were transferred to anaerobic cabinet, media replaced with reduced cRPMI and bacteria added to the cultures, 1x107CFU per well. Bacteria and cells were cocultured for 16h.

[0348] After co-culture, plates were transferred back to aerobic conditions, media removed and transwells were transferred to plates seeded with macrophages. HK ST was added to the top of the transwell at a concentration equivalent to 1x107CFU per well.

[0349] Monocyte-derived macrophages (moMac) were obtained from peripheral blood mononuclear cells (PBMC). Briefly, PBMC were isolated from human blood leukocytes cones (NHS) using Histopaque-1077 Hybri-Max (Sigma) and CD14+ monocytes were then obtained using human CD14 microbeads, LS columns and a QuadroMACS separator (Miltenyi), following manufacturer’s instructions. Differentiation of monocytes into moMac was achieved by culturing monocytes for 6 days in cRPMI supplemented with 1% Penicilin / Streptomycin (P / S, Gibco) and 50ng / ml M-CSF (Miltenyi). Macrophages were then harvested, counted, and seeded into 24-well plates, 3x105cells / well in cRPMI + P / S, 24h before co-culture with Caco-2 cells.

[0350] Caco-2 cells-moMac co-culture was maintained for 24h and supernatants was collected. Pro-inflammatory cytokines IL-1b, IL-6 and TNF-a were measured by ELISA (DuoSet ELISA kits, BioTechne), following manufacturer’s instruction.

[0351] Radiation enteritis organoid model

[0352] Organoid cultures Colonic organoid cultures were established by isolating crypts from colon resection material. Briefly, colonic tissues samples were cut into small pieces and washed with ice-cold DPBS supplemented with Antibiotic Antimycotic Solution (DPBS-AA, Sigma). Tissue fragments were transferred to a tube containing ice-cold 2.5mM ethylenediaminetetraacetic acid (EDTA) in DPBS and incubated for 45 minutes on ice, with shaking. After incubation, tissue was transferred to a fresh tube with DPBS-AA and shaken vigorously to dislodge crypts. This step was repeated twice.

[0353] Crypts were centrifuged for 2 minutes at 90 xg, 4°C and resuspended in Matrigel (Corning) before seeding onto 6-well tissue culture plates. Plates were incubated at 37°C for 5 minutes to allow Matrigel to set before addition of Organoid Growth Medium (OGM, IntestiCult, StemCell technologies) supplemented with 50mg / ml Primocin (Invivogen) and 1mM Y-27632 (Sigma).

[0354] Organoid cultures were maintained by media changing every 3 days and splitting by mechanical dissociation every 10 days. Supplements (Primocin and Y-27632) were removed after the first split.

[0355] Radiation model

[0356] For the radiation assay, organoids were harvest while still immature (cystic, budding structures just starting to appear) and seeded onto microinjection dishes (Ibidi) 24h before microinjection. Composition G was microinjected into the organoids using a FemtoJet and TransferMan (Eppendorf) on a Zeiss microscope with environmental chamber. Organoids were then incubated for 1 h before changing media to OGM supplemented with 50mg / ml Gentamicin (Sigma).

[0357] Twenty-four hours post-microinjection the organoid cultures were irradiated with a dose of 10Gy on a CellRad X-ray irradiator (Presicion). A non-bacteria treated, irradiated control was taken, as well as a non-bacteria, non-irradiated control.

[0358] Organoids, treated and controls, were incubated for 48h post-irradiation before pictures were taken for organoid phenotyping and harvesting for RNA extraction. For phenotyping the organoids, the number of cystic (no budding structures), budding (budding structures appearing), mature (fully differentiated, but clear lumen) and filled (filled lumen) were counted.

[0359] Cell adhesion molecules (ZO-1, Occludin, Claudins 1, 2, 4 and 5, Dsc2, Dsg2 and E-cadherin) and stem cell markers (Lgr5) gene expression was determined by qPCR using TaqMan Gene expression assays and 1-Step RNA-to-Ct kit (ThermoFisher). Analysis was done using the DDCt method.

[0360] Organoid-based permeability model

[0361] For the permeability assay organoids were harvested while still immature and dissociated into single cells using TyrpLE (ThermoFisher). Cells were then seeded onto 24-well plate transwells coated with collagen I (ThermoFisher, 50mg / ml in acetic acid 0.02M), 1x105cells / transwell in OGM supplemented with Y-27632. Cells were incubated until the monolayer was closed and transepithelial electrical resistance (TEER) was stable. Media was changed every other day and Y-27632 was removed after the second media change. TEER was measure using a Voltohmeter (EVOM2, WPI).

[0362] Once the monolayer was ready, cells were treated with 8% Dextran Sodium Sulphate (DSS) for 24h. Untreated wells were used as controls. After treatment, supernatant was removed and replaced by OGM or OGM plus bacteria, 1x107CFU per well. Bacteria and cells were co-cultured for 24h.

[0363] After incubation, monolayers were rinsed with HBSS (ThermoFisher) and FITC-Dextran (Sigma, 1mg / ml) was added to the top (apical) of the transwell. Plates were incubated for4h before 50ul samples were taken from the bottom (basal) of the transwell, transferred to a blank 96-well plate and fluorescence (490 / 520nm) was measured on a Sparkcontrol TECAN plate reader. Permeation rate was calculated as:

[0364] Permeation rate = apical fluorescence / basal fluorescence

[0365] References

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[0367] 2. Darwich, A. S.; Aslam, U.; Ashcroft, D. M.; Rostami-Hodjegan, A. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans. Drug Metab Dispos 2014, 42, 2016-2022, doi: 10.1124 / dmd.114.058404.

[0368] 3. Nejdfors, P.; Ekelund, M.; Westrom, B. R.; Willen, R.; Jeppsson, B. Intestinal permeability in humans is increased after radiation therapy. Dis Colon Rectum 2000, 43, 1582-1587; discussion 1587-1588, doi:10.1007 / BF02236743.

[0369] 4. Shukla, P. K.; Gangwar, R.; Manda, B.; Meena, A. S.; Yadav, N.; Szabo, E.; Balogh, A.; Lee, 5. C.; Tigyi, G.; Rao, R. Rapid disruption of intestinal epithelial tight junction and barrier dysfunction by ionizing radiation in mouse colon in vivo: protection by N-acetyl-l-cysteine. Am J Physiol Gastrointest Liver Physiol 2016, 310, G705-715, doi: 10.1152 / ajpgi.00314.2015.

[0370] 5. Crawford, P. A.; Gordon, J. I. Microbial regulation of intestinal radiosensitivity. Proc Natl Acad Sci U SA 2005, 102, 13254-13259, doi:10.1073 / pnas.0504830102.

[0371] 6. Wang, Z.; Wang, Q.; Wang, X.; Zhu, L.; Chen, J.; Zhang, B.; Chen, Y.; Yuan, Z. Gut microbial dysbiosis is associated with development and progression of radiation enteritis during pelvic radiotherapy. J Cell Mol Med 2019, 23, 3747-3756, doi:10.1111 / jcmm.14289.

[0372] 7. Cui, M.; Xiao, H.; Li, Y.; Zhou, L.; Zhao, S.; Luo, D.; Zheng, Q.; Dong, J.; Zhao, Y.; Zhang, X.; et al. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med 2017, 9, 448-461, doi:10.15252 / emmm.2O1606932. 8. Ding, X.; Li, Q.; Li, P.; Chen, X.; Xiang, L.; Bi, L.; Zhu, J.; Huang, X.; Cui, B.; Zhang, F. Fecal microbiota transplantation: A promising treatment for radiation enteritis? Radiother Oncol 2020, 143, 12-18, doi:10.1016 / j.radonc.2020.01.011.

[0373] 9. Schreiber, F.; Balas, I.; Robinson, M. J.; Bakdash, G. Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function. Cells 2024, 13, doi: 10.3390 / cells13060477.

[0374] Table 4 Sequences 16S rDNA

[0375] SEQ ID NO 1 Senegalizoassilia anaerobia ACGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTC GAACGATGAAACCGCCCTCGGGCGGACATGAAGTGGCGAACGGGTGAGTAACACGTGACC GACCTGCCCCCCGCCCAGGGACAGCCCCCCGAAAGGGGGATTAATACCTGGTACTCCGGA AGCGGCGCATGCCGCATCCGGGAAAGCTTATCGCGGCGGGGGATGGGGTCGCGGCCCATC AGGTAGACGGCGGGGCGACGGCCCACCGTGCCGACGACGGGTAGCCGGGTTGAGAGACCG ACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAAT TTTGCGCAATGGGGGCAACCCTGACGCAGCAACGCCGCGTGCGGGACGAAGGCGTCCGCG TCGTAAACCGCTTTCAGCGGGGAACACTTATCGAGGGTACCCGCAGAAGAAGCCCCGGCT AAATACGTGCCAGCAGCCGCGGTAATACGTATGGGGCGAGCGTTATCCGGATTCATTGGG CGTAAAGCGCGCGTAGGCGGAGCGCTAAGCGGGACCTCTAACCCGAGGGCTCAACCCCCG GCCGGGTCCCGAACTGGCGCTCTCGAGTGCGGTAGGGGAGAGCGGAATTCCCGGTGTAGC GGTGGAATGCGCAGATATCGGGAAGAACACCGACGGCGAAGGCAGCTCTCTGGGCCGAAA CTGACGCTGAGGCGCGAAAGCTGGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCCAG CCGTAAACGATGGGCGCTAGGTGTGGGGGGGAAGACCCCCCGTGCCGCAGCCAACGCATT AAGCGCCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGGAATTGACGGGGGCC CGCACAAGCAGCGGAGCATGTGGCTTAATTCGAAGCAACGCGAAGAACCTTACCAGGGCT T GAG AT GC GGGT GAAGC GGC GGAGAC GCC GT GGCC GAGAGGAGCCC GC AC AGGT GGT GC A TGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCC TGCCCCGTGTTGCCAGCATTCAGTTGGGGACTCGCGGGGGACTGCCGGCGTCAAGCCGGA GGAAGGTGGGGACGACGTCAAGTCATCATGCCCCTTATGCCCTGGGCCGCACACGTGCTA CAATGGCCGGTACAGAGGGTTGCGACCCCGCGAGGGGGAGCGGATCCCGCAAAGCCGGCC CCAGTTCGGATCGGAGGCTGCAACCCGCCTCCGTGAAGCCGGAGTTGCTAGTAATCGCGG ATCAGCACGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACCC GAGTCGTCTGCACCCGAAGCCGCCGGCCGAACCCTTTCAGGGGCGGAGGCGTCGAAGGTG TGGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGATC ACCTCCTTT SEQ ID NO 2 Christensenellaceae R-7 Sp.

[0376] AAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAG CGGAGACAGTGAGTAGCTTGCTACTGATTGTTTTAGCGGCGGACGGGTGAGTAACGCGTG AGCAACCTTTCCCAGACAGGGGAATAACACACCGAAAGGTGTACTAATACCGCATAAGAC CACGGGATCACATGGTTCTGGGGTAAAAGAATTATCGGTTTGGGGTGGGCTCGCGTCCGA TTAGGTAGTTGGTGAGGTAACGGCCCACCAAGCCGACGATCGGTAGCCGACCTGAGAGGG TGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGA ATATTGGGCAATGGAGGAAACTCTGACCCAGCAACGCCGCGTGGAGGAAGAAGGTTTTCG GATCGTAAACTCCTGTCCTTGGAGACGAGTAGAAGACGGTATCCAAGGAGGAAGCCCCGG CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTGTCCGGAATAATTG GGCGTAAAGGGCGCGTAGGCGGCTCGGTAAGTCTGGAGTGAAAGTCCTGCTTTTAAGGTG GGAATTGCTTTGGATACTGTCGGGCTTGAGTGCAGGAGAGGTTAGTGGAATTCCCAGTGT AGCGGTGAAATGCGTAGAGATTGGGAGGAACACCAGTGGCGAAGGCGACTAACTGGACTG TAACTGACGCTGAGGCGCGAAAGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCC ACACTGTAAACGATGAATGCTAGGTGTAGGGGGTATCGACCCCTTCTGTGCCGCAGTCAA CACAATAAGCATTCCGCCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACG GGGGCCCGCACAAGCAGCGGAGCATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACC AGGT CT T GAC AT CC AC T T AAACT T AC AGAGAT GT AAGGT GT GCT T GC AC AAAGT GAGAC A GGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG CGCAACCCTTATCTTCAGTTACTAACGCGTAGAGGTGAGGACTCTGAAGAGACTGCCGGG GACAACTCGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTA CACACGTGCTACAATGGCCACGACAGAGAGAAGCGAAATCGTAAGGTGGAGCGGAACTCA AAAAAGTGGTCCCAGTTCGGATTGTGGGCTGCAACCCGCCCACATGAAGTCGGAGTTGCT AGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG TCACACCATGGGAGTTGGGAGTGCCCAAAGCCGGTGAGGCAACCGCAAGGAGCCAGCCGT CTAAGGCAAGACCAATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG GCTGGATCACCTCCTTT SEQ ID NO 3 Prevotella copri ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC GAGGGGAAACGATATTGGAAGCTTGCTTCCGATAGGCGTCGACCGGCGCACGGGTGAGTA ACGCGTATCCAACCTGCCCACCACTTGGGGATAACCTTGCGAAAGTAAGACTAATACCCA ATGACGTCTCTAGAAGACATCTGAAAGAGATTAAAGATTTATCGGTGATGGATGGGGATG CGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCAACGATCAGTAGGGGTTCT GAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCA GT GAGGAAT AT T GGT C AAT GGAC GAGAGT CT GAAC C AGC C AAGT AGC GT GC AGGAT GAC G GCCCTATGGGTTGTAAACTGCTTTTATAAGGGAATAAAGTGAGTCTCGTGAGACTTTTTG CATGTACCTTATGAATAAGGACCGGCTAATTCCGTGCCAGCAGCCGCGGTAATACGGAAG GTCCGGGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCCGGAGATTAAGCGTG TTGTGAAATGTAGACGCTCAACGTCTGCACTGCAGCGCGAACTGGTTTCCTTGAGTACGC AC AAAGT GGGC GGAAT T C GT GGT GT AGC GGT GAAAT GCT T AGAT AT C AC GAAGAACT C C G ATTGCGAAGGCAGCTCACTGGAGCGCAACTGACGCTGAAGCTCGAAAGTGCGGGTATCGA ACAGGATTAGATACCCTGGTAGTCCGCACGGTAAACGATGGATGCCCGCTGTTGGTCTGA ATAGGTCAGCGGCCAAGCGAAAGCATTAAGCATCCCACCTGGGGAGTACGCCGGCAACGG TGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA TGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAGAGGAAGGATTTGGAGACAATGAC GCCCTTCGGGGCCTCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGT CGGCTTAAGTGCCATAACGAGCGCAACCCCTCTCCTTAGTTGCCATCAGGTTAAGCTGGG CACT CT GGGGAC ACT GCCACCGT AAGGT GT GAGGAAGGT GGGGAT GAC GT CAAATCAGCA CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGCAGGTACAGAGAGACGGTCCCT TGCAAAATGGATCAAATCCTTAAAGCCTGTCTCAGTTCGGACTGGGGTCTGCAACCCGAC CCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCC GGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGCGCCTAAAGTCCGTGACC GTAAGGAGCGGCCTAGGGCGAAACTGGTAATTGGGGCTAAGTCGTAACAAGGTAGCCGTA CCGGAAGGTGCGGCTGGAACACCTCCTTT

[0377] SED ID NO 4 Barnesiella intestinihominis CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCCTAACACATGCAAGTCG AGGGGCAGCGGAGAGGTAGCAATACCTTTGCCGGCGACCGGCGCACGGGTGAGTAACACG TATGCAATCCACCTGTAACAGGGGGATAACCCGGAGAAATCCGGACTAATACCCCATAAT ATGGGCGCTCCGCATGGAGAGTCCATTAAAGAGAGCAATTTTGGTTACAGACGAGCATGC GCTCCATTAGCCAGTTGGCGGGGTAACGGCCCACCAAAGCGACGATGGATAGGGGTTCTG AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAG TGAGGAATATTGGTCAATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAGGGAAGACGG CCCTACGGGTTGTAAACCTCTTTTGTCGGAGAGTAAAGTACGCTACGTGTAGTGTATTGC AAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGA TGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCACGCCAAGTCAGC GGTGAAATTTCCGGGCTCAACCCGGACTGTGCCGTTGAAACTGGCGAGCTAGAGTGCACA AGAGGCAGGCGGAAT GCGT GGT GT AGC GGT GAAAT GCAT AGAT ATC ACGC AGAACCCC GA TTGCGAAGGCAGCCTGCTAGGGTGCGACAGACGCTGAGGCACGAAAGCGTGGGTATCGAA CAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGAATACTAACTGTTTGCGATAC AATGTAAGCGGTACAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGAT GATACGCGAGGAACCTTACCCGGGCTCAAACGCAGGGGGAATGCCGGTGAAAGTCGGCAG CTAGCAATAGTCACCTGCGAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTC GGCTTAAGTGCCATAACGAGCGCAACCCCTATGGACAGTTACTAACGGGTGAAGCCGAGG ACTCTGTCTAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCAAATCAGCAC GGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGAAGGCAGCCAGTCA GC AAT GAG GC GC GAAT C C C G AAAAC C T GT C T C AGT T C GG AT T GGAGT C T GC AAC C C GAG T CCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCCG GGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGTACCTGAAGCATGCAACCG CAAGGAGCGTACGAAGGTAATACCGGTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTTT

[0378] SEQ ID NO. 5 Senegalimassilia anaerobia ACGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAACGATGAAACCGC CCTCGGGCGGACATGAAGTGGCGAACGGGTGAGTAACACGTGACCGACCTGCCCCCCGCCCAGGGACAGCCCCCC GAAAGGGGGATTAATACCTGGTACTCCGGAAGCGGCGCATGCCGTCTCCGGGAAAGCTTATCGCGGCGGGGGATG GGGTCGCGGCCCATCAGGTAGACGGCGGGGCGACGGCCCACCGTGCCGACGACGGGTAGCCGGGTTGAGAGACCG ACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATTTTGCGCAATGGGGG CAACCCTGACGCAGCAACGCCGCGTGCGGGACGAAGGCGTCCGCGTCGTAAACCGCTTTCAGCGGGGAACACTTW TCGAGGGTACCCGCAGAAGAAGCCCCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGGGCGAGCGTTA TCCGGATTCATTGGGCGTAAAGCGCGCGTAGGCGGAGCGCTAAGCGGGACCTCTAACCCGAGGGCTCAACCCCCG GCCGGGTCCCGAACTGGCGCTCTCGAGTGCGGTAGGGGAGAGCGGAATTCCCGGTGTAGCGGTGGAATGCGCAGA TATCGGGAAGAACACCGACGGCGAAGGCAGCTCTCTGGGCCGAAACTGACGCTGAGGCGCGAAAGCTGGGGGAGC GAACAGGATTAGATACCCTGGTAGTCCCAGCCGTAAACGATGGGCGCTAGGTGTGGGGGGGAAGACCCCCCGTGC CGCAGCCAACGCATTAAGCGCCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGGAATTGACGGGGGCC CGCACAAGCAGCGGAGCATGTGGCTTAATTCGAAGCAACGCGAAGAACCTTACCAGGGCTTGACATRYRGGTGAA GCGGCGGAGACGCCGTGGCCGAGAGGAGCCCGCACAGGTGGTGCATGGCTGTCGTCAGCTCGTGTCGTGAGATGT TGGGTTAAGTCCCGCAACGAGCGCAACCCCTGCCCCGTGTTGCCAGCATTCAGTTGGGGACTCGCGGGGGACTGC CGGCGTCAAGCCGGAGGAAGGTGGGGACGACGTCAAGTCATCATGCCCCTTATGCCCTGGGCCGCACACGTGCTA CAATGGCCGGTACAGAGGGTTGCGACCCCGCGAGGGGGAGCGGATCCCGCAAAGCCGGCCCCAGTTCGGATCGGA GGCTGCAACCCGCCTCCGTGAAGCCGGAGTTGCTAGTAATCGCGGATCAGCACGCCGCGGTGAATACGTTCCCGG GCCTTGTACACACCGCCCGTCACACCACCCGAGTCGTCTGCACCCGAAGCCGCCGGCCGAACCCTTTCAGGGGCG GAGGCGTCGAAGGTGTGGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGATC ACCTCCTTT SEQ ID NO 6 Christensenellaceae R-7 Sp.

[0379] AAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAG CGGAGACAGTGAGTAGCTTGCTATGAGCTGTTTTAGCGGCGGACGGGTGAGTAACGCGTG AGCAACCTTTCCCAGACAGGGGAATAACACACCGAAAGGTGTACTAATACCGCATAAGAC CACGGGATCACATGGTTCTGGGGTAAAAGATTTATCGGTTTGGGGTGGGCTCGCGTCCGA TTAGGTAGTTGGTGAGGTAACGGCCCACCAAGCCGACGATCGGTAGCCGACCTGAGAGGG TGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGA ATATTGGGCAATGGGGGGAACCCTGACCCAGCAACGCCGCGTGGAGGAAGAAGGTTTTCG GATCGTAAACTCCTGTCCTTGGAGACGAGTAGAAGACGGTATCCAAGGAGGAAGCCCCGG CTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGTTGTCCGGAATAATTG GGCGTAAAGGGCGCGTAGGCGGCTCGGTAAGTCTGGAGTGAAAGTCCTGCTTTTAAGGTG GGAATTGCTTTGGATACTGTCGGGCTTGAGTGCAGGAGAGGTTAGTGGAATTCCCAGTGT AGCGGTGAAATGCGTAGAGATTGGGAGGAACACCAGTGGCGAAGGCGACTAACTGGACTG TAACTGACGCTGAGGCGCGAAAGTGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCC ACACTGTAAACGATGAATGCTAGGTGTAGGGGGTATCGACCCCTTCTGTGCCGCAGTTAA CACAATAAGCATTCCGCCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACG GGGGCCCGCACAAGCAGCGGAGCATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACC AGGTCTTGACATCCAGTAAAACTTGTAGAGATACAAGGTGAGCTTGCTCATACTGAGACA GGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG CGCAACCCTTATCTTCAGTTACTAACGCGTAGAGGTGAGGACTCTGAAGAGACTGCCGGG GACAACTCGGAGGAAGGTGGGGACGACGTCAAATCATCATGCCCCTTATGACCTGGGCTA GAG AC GT GCT AC AAT GGCC AC GAC AGAGAGAAGC GAAAT C GC AAGGT AGAGC GGAACT C A AAAAAGTGGTCCCAGTTCGGATTGTGGGCTGCAACCCGCCCACATGAAGTCGGAGTTGCT AGTAATCGCGGATCAGCATGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCG TCACACCATGGGAGTTGGGAGTGCCCAAAGCCGGTGAGGCAACCGCAAGGAGCCAGCCGT CTAAGGCAAGACCAATGACTGGGGTGAAGTCGTAACAAGGTAGCCGTATCGGAAGGTGCG GCTGGATCACCTCCTTT SEQ Id No. 7 Christensenellaceae R-7 group species AAGAGTTTGATCCTGGCTCAGGACGAACGCTGGCGGCGTGCCTAACACATGCAAGTCGAGCGGAGACAGTGAGTA GCTTGCTAYGAGCTGTTTTAGCGGCGGACGGGTGAGTAACGCGTGAGCAACCTTTCCCAGACAGGGGAATAACAC ACCGAAAGGTGTACTAATACCGCATAAGACCACGGKWTCACATGGKWCTGRGGTAAAAGATTTATCGGTTTGGGG TGGGCTCGCGTCCGATTAGGTAGTTGGTGAGGTAACGGCCCACCAAGCCGACGATCGGTAGCCGACCTGAGAGGG TGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGAATATTGGGCAATGGR GGRAACYCTGACCCAGCAACGCCGCGTGGAGGAAGAAGGTTTTCGGATCGTAAACTCCTGTCCTTGGAGACGAGT AGAAGACGGTATCCAAGGAGGAAGCCCCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCAAGCGT TGTCCGGAATAATTGGGCGTAAAGGGCGCGTAGGCGGCTCGGTAAGTCTGGAGTGAAAGTCCTGCTTTTAAGGTG GGAATTGCTTTGGATACTGTCGGGCTTGAGTGCAGGAGAGGTTAGTGGAATTCCCAGTGTAGCGGTGAAATGCGT AGAGATTGGGAGGAACACCAGTGGCGAAGGCGACTAACTGGACTGTAACTGACGCTGAGGCGCGAAAGTGTGGGG AGCAAACAGGATTAGATACCCTGGTAGTCCACACTGTAAACGATGAATGCTAGGTGTAGGGGGTATCGACCCCTT CTGTGCCGCAGTCAACACAATAAGCATTCCGCCTGGGGAGTACGGCCGCAAGGTTGAAACTCAAAGGAATTGACG GGGGCCCGCACAAGCAGCGGAGCATGTGGTTTAATTCGACGCAACGCGAAGAACCTTACCAGGTCTTGACATCCA CTTAAACTTACAGAGATGTAAGGTGTGCTTGCACAAAGTGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTC GTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTATCTTCAGTTACTAACG

[0380] SEQ ID NO 8 Prevotella copri ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC GAGGGGAAACGACATCGAAAGCTTGCTTTTGATGGGCGTCGACCGGCGCACGGGTGAGTA ACGCGTATCCAACCTGCCCACCACTTGGGGATAACCTTGCGAAAGTAAGACTAATACCCA AT GAT T CT CT GAAGACAT CT GAAAGAGATTAAAGATTT T CGGT GAT GGAT GGGGAT G CGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCGACGATCAGTAGGGGTTCT GAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCA GTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGCAGGATGACG GCCCTATGGGTTGTAAACTGCTTTTATAAGGGAATAAAGTGAGTCTCGTGAGACTTTTTG CATGTACCTTATGAATAAGGACCGGCTAATTCCGTGCCAGCAGCCGCGGTAATACGGAAG GTCCGGGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCCGGAGATTAAGCGTG TTGTGAAATGTAGACGCTCAACGTCTGCACTGCAGCGCGAACTGGTTTCCTTGAGTACGC ACAAAGTGGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCG ATTGCGAAGGCAGCTCACTGGAGCGCAACTGACGCTGAAGCTCGAAAGTGCGGGTATCGA ACAGGATTAGATACCCTGGTAGTCCGCACGGTAAACGATGGATGCCCGCTGTTGGTCTGA ATAGGTCAGCGGCCAAGCGAAAGCATTAAGCATCCCACCTGGGGAGTACGCCGGCAACGG TGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA TGATACGCGAGGAACCTTACCCGGGCTTGAATTGCAGAGGAAGGATTTGGAGACAATGAC GCCCTTCGGGGCCTCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGT CGGCTTAAGTGCCATAACGAGCGCAACCCCTCTCCTTAGTTGCCATCAGGTCACGCTGGG CACTCTGGGGACACTGCCACCGTAAGGTGTGAGGAAGGTGGGGATGACGTCAAATCAGCA CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGCAGGTACAGAGAGATGGTCCCT TGCAAAATGGATCAAATCCTTAAAGCCTGTCTCAGTTCGGACTGGGGTCTGCAACCCGAC CCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCC GGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGCGCCTAAAGTCCGTGACC GTAAGGAGCGGCCTAGGGCGAAACTGGTAATTGGGGCTAAGTCGTAACAAGGTAGCCGTA CCGGAAGGTGCGGCTGGAACACCTCCTTT

[0381] SEQ ID NO 9 Prevotella. copri ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTC GAGGGGAAACGACATCGAAAGCTTGCTTTTGATGGGCGTCGACCGGCGCACGGGTGAGTA ACGCGTATCCAACCTGCCCGCCACTTGGGGATAACCTTGCGAAAGTAAGACTAATACCCA ATGATATCTCTAGAAGGCATCTGAAAGAGATTAAAGATTTATCGGTGATGGATGGGGATG CGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCAACGATCAGTAGGGGTTCT GAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCA GT GAGGAAT T T GGT C AT GGAC GAGAGT CT GAAC C GC C AGT GC GT GC GGAAGAC G GCCCTATGGGTTGTAAACTGCTTTTATAAGGGAATAAAGTGAGTCTCGTGAGACTTTTTG CATGTACCTTATGAATAAGGACCGGCTAATTCCGTGCCAGCAGCCGCGGTAATACGGAAG GTCCGGGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCCGGAGATTAAGCGTG T T GT GAAAT GT GAT GCT C AC T CT GAACT GC GC GC GAAC T GGT T T CC T T GAGT C GC AC AAGT GGGC GGAAT T C GT GGT GT GC GGT GAAAT GCT T GAT T C C GAAGAACT C C G ATTGCGAAGGCAGCTCACTGGAGCGCAACTGACGCTGAAGCTCGAAAGTGCGGGTATCGA ACAGGATTAGATACCCTGGTAGTCCGCACGGTAAACGATGGATGCCCGCTGTTGGTCTGA ATAGGTCAGCGGCCAAGCGAAAGCATTAAGCATCCCACCTGGGGAGTACGCCGGCAACGG TGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGA TGAT CGCGAGGAACCTTACCCGGGCTTGAATTGCAGAGGAAGGATTTGGAGACAATGAC GCCCTTCGGGGCCTCTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGT CGGCTTAAGTGCCATAACGAGCGCAACCCCTCTCCTTAGTTGCCATCAGGTGAAGCTGGG C CT CT GGGGAC CT GCC CCGT AGGT GT GAGGAAGGT GGGGAT GACGT CAAATC GC CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGCAGGTACAGAGAGACGGTCCCT TGCAAAATGGATCAAATCCTTAAAGCCTGTCTCAGTTCGGACTGGGGTCTGCAACCCGAC CCCACGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCATGGCGCGGTGAATACGTTCCC GGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGCGCCTAAAGTCCGTGACC GTAAGGAGCGGCCTAGGGCGAAACTGGTAATTGGGGCTAAGTCGTAACAAGGTAGCCGTA CCGGAAGGTGCGGCTGGAACACCTCCTTT SEQ ID NO. 10 Prevotella copri ATGGAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGAAACGAYAT YGRAAGCTTGCTTYYGATRGGCGTCGACCGGCGCACGGGTGAGTAACGCGTATCCAACCTGCCCAYCACTTGGGG ATAACCTTGCGAAAGTAAGACTAATACCCAATGAYRTCTCTAGAAGACATCTGAAAGAGATTAAAGATTYATCGG TGATGGATGGGGATGCGTCTGATTAGCTTGTTGGCGGGGTAACGGCCCACCAAGGCRACGATCAGTAGGGGTTCT GAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGT CAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGCAGGAWGACGGCCCTATGGGTTGTAAACTGCTTTTATAAG GGAATAAAGTGAGWSTCGTGASWCTTTTTGCATGTACCTTATGAATAAGGACCGGCTAATTCCGTGCCAGCAGCC GCGGTAATACGGAAGGTCCGGGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCCGGAGATTAAGCGTG TTGTGAAATGTAGAYGCTCAACRTCTGMACTGCAGCGCGAACTGGTTTCCTTGAGTACGCACAAAGTGGGCGGAA TTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTCACTGGAGCGCAACT GACGCTGAAGCTCGAAAGTGCGGGTATCGAACAGGATTAGATACCCTGGTAGTCCGCACGGTAAACGATGGATGC CCGCTGTTGGTCTGAATAGGTCAGCGGCCAAGCGAAAGCATTAAGCATCCCACCTGGGGAGTACGCCGGCAACGG TGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAAC CTTACCCGGGCTTGAATTGCAGAGGAAGGATTTGGAGACAATGACGCCCTTCGGGGCCTCTGTGAAGGTGCTGCA TGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTCTCCTTAGTTGCCA TCAGGTYAWGCTGGGCACTCTGGGGACACTGCCACCGTAAGGTGTGAGGAAGGTGGGGATGACGTCAAATCAGCA CGGCCCTTACGTCCGGGGCTACACACGTGTTACAATGGCAGGTACAGAGAGACGGTCCCTTGCAAAATGGATCAA ATCCTTAAAGCCTGTCTCAGTTCGGACTGGGGTCTGCAACCCGACCCCACGAAGCTGGATTCGCTAGTAATCGCG CATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGCGC CTAAAGTCCGTGACCGTAAGGAGCGGCCTAGGGCGAAACTGGTAATTGGGGCTAAGTCGTAACAAGGTAGCCGTA CCGGAAGGTGCGGCTGGAACACCTCCTTT

[0382] SEQ ID NO. 11 Barniesiella intestinihominis 16S DNA sequence CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCCTAACACATGCAAGTCGAGGGGCAGCGRRGAG GTAGCAATACCTTTGYCGGCGACCGGCGCACGGGTGAGTAACACGTATGCAATCCACCTGTAACAGGGGGATAAC CCGGAGAAATCCGGACTAATACCCCATRATATGGGCKCTCCGCATGGAGRGYCCATTAAAGAGAGCAATYTTGGT TACAGACGAGCATGCGCTCCATTAGCCAGTTGGCGGGGTAACGGCCCACCAARGCGACGATGGATAGGGGTTCTG AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTC AATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTAAACCTCTTTTGTCGGA GAGTAAAGTRCGCTACGYGTAGYGTATTGCAAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGCCG CGGTAATACGGAGGATGCRAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCACGCCAAGTCAGC GGTGAAATTTCCGGGCTCAACCCGGAGTGTGCCGTTGAAACTGGCGAGCTAGAGTRCACAAGAGGCAGGCGGAAT GCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCTAGGGTGAAACAG ACGCTGAGGCACGAAAGCGTGGGTATCGAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGAATACT AACTGTTTGCGATACAATGTAAGCGGTACAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACC TTACCCGGGCTCAAACGCAGGGGGAATGCCGGTGAAAGCCGGCAGCTAGCAATAGTCACCTGCGAGGTGCTGCAT GGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTATGGACAGTTACTAA CGGGTCAAGCCGAGGACTCTGTCGAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCAAATCAGCAC GGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGAAGGCAGCCAGTCAGCAATGACGCGCGAA TCCCGAAAACCTGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGC ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGTACC TGAAGCATGCAACCGCAAGGAGCGTACGAAGGTAATACCGGTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTTT

[0383] SEQ ID NO 12 Bifidobacterium adolescentis TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGT CGAACGGGATCCCAGGAGCTTGCTCCTGGGTGAGAGTGGCGAACGGGTGAGTAATGCGTG ACCGACCTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTCC AGTTGACCGCATGGTCCTCTGGGAAAGCTTTTGCGGTATGGGATGGGGTCGCGTCCTATC AGCTTGATGGCGGGGTAACGGCCCACCATGGCTTCGACGGGTAGCCGGCCTGAGAGGGCG ACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAAT ATTGCACAATGGGCGCAAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCGGG TTGTAAACCGCTTTTGACTGGGAGCAAGCCCTTCGGGGTGAGTGTACCTTTCGAATAAGC ACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTGCAAGCGTTATCCGGAAT TATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCTTA ACGGTGGATCCGCGCCGGGTACGGGCGGGCTTGAGTGCGGTAGGGGAGACTGGAATTCCC GGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTG GGCCGTCACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGT AGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGACCATTCCACGGTCTCCGTGTCGG AGCCAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAA T T GAG GGGGGCC C GC C AGC GGC GGAGC T GC GG T T AT T C GAT GC AC GC GAAGAAC CTTACCTGGGCTTGACATGTTCCCGACAGCCCCAGAGATGGGGCCTCCCTTCGGGGCGGG TTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGC AACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCGTGGTGGGAACTCACGGGGGACC GCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCA GGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACCGCGAGGTGGAGCGG ATCCCTTAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGA GTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACA CCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTGGCCCAACCTTTTGGGGG GAGCCGTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCGGA AGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 13 Bifidobacterium adolescentis TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGT CGAACGGGATCCCAGGAGCTTGCTCCTGGGTGAGAGTGGCGAACGGGTGAGTAATGCGTG ACCGACCTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTCC AGTTGACCGCATGGTCCTCTGGGAAAGCTTTTGCGGTATGGGATGGGGTCGCGTCCTATC AGCTTGATGGCGGGGTAACGGCCCACCATGGCTTCGACGGGTAGCCGGCCTGAGAGGGCG ACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAAT ATTGCACAATGGGCGCAAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCGGG TTGTAAACCGCTTTTGACTGGGAGCAAGCCCTTCGGGGTGAGTGTACCTTTCGAATAAGC ACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTGCAAGCGTTATCCGGAAT TATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCTTA ACGGTGGATCCGCGCCGGGTACGGGCGGGCTTGAGTGCGGTAGGGGAGACTGGAATTCCC GGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTG GGCCGTCACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGT AGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGACCATTCCACGGTCTCCGTGTCGG AGCCAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAA T T GAG GGGGGCC C GC AC AAGC GGC GGAGC AT GC GGAT T AAT T C GAT GC AAC GC GAAGAAC CTTACCTGGGCTTGACATGTTCCCGACAGCCCCAGAGATGGGGCCTCCCTTCGGGGCGGG TTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGC AACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCGTGGTGGGAACTCACGGGGGACC GCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCA GGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACCGCGAGGTGGAGCGG ATCCCTTAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGA GTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACA CCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTGGCCCAACCTTTTTGGGG GGAGCCGTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCGG AAGGTGCGGCTGGATCACCTCCTTT SEQ ID No. 14 Bifidobacterium adolescentis TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAACGGGATCGGCT GGAGCTTGCTCCGGCCGTGAGAGTGGCGAACGGGTGAGTAATGCGTGACCGACCTGCCCCATACACCGGAATAGC TCCTGGAAACGGGTGGTAATGCCGGATGCTCCAGTTGGATGCATGTCCTTCTGGGAAAGATTCATCGGTATGGGA TGGGGTCGCGTCCTATCAGCTTGATGGCGGGGTAACGGCCCACCATGGCTTCGACGGGTAGCCGGCCTGAGAGGG CGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGG CGCAAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCGGGTTGTAAACCGCTTTTGACTGGGAGCAAG CCCTTCGGGGTGAGTGTACCTTTCGAATAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTG CAAGCGTTATCCGGAATTATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCT TAACGGTGGATCCGCGCCGGGTACGGGCGGGCTTGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGG AATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTCACTGACGCTGAGGAGCGAAAG CGTGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGACCATTC CACGGTCTCCGTGTCGGAGCCAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGA AATTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCTTACCTGGGCTT GACATGTTCCCGACAGCCSYAGAGATRSGGYCTCCCTTCGGGGCGGGTTCACAGGTGGTGCATGGTCGTCGTCAG CTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCGTGGTG GGAACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTC CAGGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACCGCGAGGTGGAGCGGATCCCTTAAAACC GGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGAGTCGCTAGTAATCGCGGATCAGCAACGC CGCGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTG GCCCAACCTTTTGGGGGGAGCCGTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCG GAAGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 15 Bifidobacterium pseudocatenulatvm TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGT CGAACGGGATCCATCAGGCTTTGCTTGGTGGTGAGAGTGGCGAACGGGTGAGTAATGCGT GACCGACCTGCCCCATACACCGGAATAGCTCCTGGAAACGGGTGGTAATGCCGGATGCTC CGACTCCTCGCATGGGGTGTCGGGAAAGATTTCATCGGTATGGGATGGGGTCGCGTCCTA TCAGGTAGTCGGCGGGGTAACGGCCCACCGAGCCTACGACGGGTAGCCGGCCTGAGAGGG CGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGA ATATTGCACAATGGGCGCAAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCG GGTTGTAAACCGCTTTTGATCGGGAGCAAGCCTTCGGGTGAGTGTACCTTTCGAATAAGC ACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTGCAAGCGTTATCCGGAAT TATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCTTA ACGGTGGATCTGCGCCGGGTACGGGCGGGCTGGAGTGCGGTAGGGGAGACTGGAATTCCC GGTGTAACGGTGGAATGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTG GGCCGTTACTGACGCTGAGGAGCGAAAGCGTGGGGAGCGAACAGGATTAGATACCCTGGT AGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGCCCGTTCCACGGGTTCCGTGTCGG AGCTAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAA T T GAG GGGGGCC C GC AC AAGC GGC GGAGC AT GC GGAT T AAT T C GAT GC AAC GC GAAGAAC CTTACCTGGGCTTGACATGTTCCCGACCGCGGCAGAGATGTCGTTTCCCTTCGGGGCGGG TTCACAGGTGGTGCATGGTCGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGC AACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCATGGTGGGAACTCACGGGGGACC GCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCA GGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACGGCGACGTGGAGCGG ATCCCTGAAAACCGGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGA GTCGCTAGTAATCGCGGATCAGCAACGCCGCGGTGAATGCGTTCCCGGGCCTTGTACACA CCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTGGCCTAACCCTTTGTGGA TGGAGCCGTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCG GAAGGTGCGGCTGGATCACCTCCTTT SEQ ID No. 16 Bifidobacterium pseudocatenulatum TGTGGAGGGTTCGATTCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAACGGGATCCATC AGGCTTTGCTTGGTGGTGAGAGTGGCGAACGGGTGAGTAATGCGTGACCGACCTGCCCCATACACCGGAATAGCT CCTGGAAACGGGTGGTAATGCCGGATGCTCCGACTCCTCGCATGGGGTGTCGGGAAAGATTTCATCGGTATGGGA TGGGGTCGCGTCCTATCAGGTAGTCGGCGGGGTAACGGCCCACCGAGCCTACGACGGGTAGCCGGCCTGAGAGGG CGACCGGCCACATTGGGACTGAGATACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGG CGCAAGCCTGATGCAGCGACGCCGCGTGCGGGATGACGGCCTTCGGGTTGTAAACCGCTTTTGATCGGGAGCAAG CCTTCGGGTGAGTGTACCTTTCGAATAAGCACCGGCTAACTACGTGCCAGCAGCCGCGGTAATACGTAGGGTGCA AGCGTTATCCGGAATTATTGGGCGTAAAGGGCTCGTAGGCGGTTCGTCGCGTCCGGTGTGAAAGTCCATCGCTTA ACGGTGGATCTGCGCCGGGTACGGGCGGGCTGGAGTGCGGTAGGGGAGACTGGAATTCCCGGTGTAACGGTGGAA TGTGTAGATATCGGGAAGAACACCAATGGCGAAGGCAGGTCTCTGGGCCGTTACTGACGCTGAGGAGCGAAAGCG TGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGGTGGATGCTGGATGTGGGGCCCGTTCCA CGGGTTCCGTGTCGGAGCTAACGCGTTAAGCATCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGAAA TTGACGGGGGCCCGCACAAGCGGCGGAGCATGCGGATTAATTCGATGCAACGCGAAGAACCTTACCTGGGCTTGA CATGTTCCCGACAGCCGTAGAGATATGGCCTCCCTTCGGGGCGGGTTCACAGGTGGTGCATGGTCGTCGTCAGCT CGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTCGCCCTGTGTTGCCAGCACGTCATGGTGGG AACTCACGGGGGACCGCCGGGGTCAACTCGGAGGAAGGTGGGGATGACGTCAGATCATCATGCCCCTTACGTCCA GGGCTTCACGCATGCTACAATGGCCGGTACAACGGGATGCGACACGGCGACGTGGAGCGGATCCCTGAAAACCGG TCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGGCGGAGTCGCTAGTAATCGCGGATCAGCAACGCCG CGGTGAATGCGTTCCCGGGCCTTGTACACACCGCCCGTCAAGTCATGAAAGTGGGTAGCACCCGAAGCCGGTGGC CTAACCCTTTGTGGATGGAGCCGTCTAAGGTGAGACTCGTGATTGGGACTAAGTCGTAACAAGGTAGCCGTACCG GAAGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 17 Eubacterium ventriosum AACGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAATACATGCAAGTC GAACGAAGCACCTTGGACAGAATCCTTCGGGAGGAAGACCATTGTGACTGAGTGGCGGAC GGGTGAGTAACGCGTGGGTAACCTGCCTTGTACAGGGGGATAACAGTTGGAAACGACTGC TAATACCGCATAAGCGCACAGTACCGCATGGTACGGTGTGAAAAACTCCGGTGGTACAAG ATGGACCCGCGTCTGATTAGCTAGTTGGTGAGGTAACGGCCCACCAAGGCGACGATCAGT AGCCGACTTGAGAGAGTGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGG GAGGC AGC AGT AGGGAAT AT T GC AC AAT GGGGGAAACCC T GAT GC AGC GAC GCC GC GT GA AGGAAGAAGTATTTCGGTATGTAAACTTCTATCAGCAAGGAAGAAAATGACGGTACTTGA CTAAGAAGCCCCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGGGCAAGCGTT ATCCGGATTTACTGGGTGTAAAGGGAGCGTAGGCGGCATGGCAAGTCAGAAGTGAAAGCC TGGGGCTCAACCCCGGAATTGCTTTTGAAACTGTCAGGCTAGAGTGTCGGAGGGGTAAGC GGAATTCCTAGTGTAGCGGTGAAATGCGTAGATATTAGGAGGAACACCGGTGGCGAAGGC GGCTTACTGGACGATTACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGA TACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGGACAATAGTTCCTC GGTGCCGAAGCAAACGCATTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACT CAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACG CGAAGAACCTTACCTGCTCTTGACATCCCACTGACAGGTCAGTAATGTGACCCTTTCTTC GGAACAGTGGAGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTT AAGTCCCGCAACGAGCGCAACCCTTGTCTTTAGTAGCCAGCAGTACGGCTGGGCACTCTA GAGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCT TACGAGCAGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGACCCCGTGAGG GTAAGCAAATCTCAAAAATAACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATG AAGCTGGAATCGCTAGTAATCGCGAATCAGAATGTCGCGGTGAATACGTTCCCGGGTCTT GTACACACCGCCCGTCACACCATGGGAGTTGGATATGCCCGAAGTCAGTGACCCAACCGT AAGGAGGGAGCTGCCGAAGGTGGAGCCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCG TATCGGAAGGTGCGGCTGGATCACCTCCTTT SEQ ID No. 18 Eubacterium ventriosum AACGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAATACATGCAAGTCGAACGAAGCACCTTG GACAGAATCCTTCGGGAGGAAGACCATTGTGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTTG TACAGGGGGATAACAGTTGGAAACGACTGCTAATACCGCATAAGCGCACAGTACCGCATGGTACGGTGTGAAAAA CTCCGGTGGTACAAGATGGACCCGCGTCTGATTAGCTGGTTGGTGAGGTAACGGCCCACCAAGGCGACGATCAGT AGCCGACTTGAGAGAGTGATCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTAGGG AATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAAGGAAGAAGTATTTCGGTATGTAAACTTCT ATCAGCAAGGAAGAAAATGACGGTACTTGACTAAGAAGCCCCGGCTAAATACGTGCCAGCAGCCGCGGTAATACG TATGGGGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGTAGGCGGCATGGCAAGTCAGAAGTGAAAGCC TGGGGCTCAACCCCGGAATTGCTTTTGAAACTGTCAGGCTAGAGTGTCGGAGGGGTAAGCGGAATTCCTAGTGTA GCGGTGAAATGCGTAGATATTAGGAGGAACACCGGTGGCGAAGGCGGCTTACTGGACGATTACTGACGCTGAGGC TCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGG GGACAATAGTTCCTCGGTGCCGAAGCAAACGCATTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACT CAAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCT GCTCTTGACATCCCACTGACAGGTCAGTAATGTGACCCTTTCTTCGGAACAGTGGAGACAGGTGGTGCATGGTTG TCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCTTGTCTTTAGTAGCCAGCAGTA CGGCTGGGCACTCTAGAGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCT TACGAGCAGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGACCCCGTGAGGGCAAGCAAATCTCAA AAATAACGTCTCAGTTCGGATTGTAGTCTGCAACTCGACTACATGAAGCTGGAATCGCTAGTAATCGCGAATCAG AATGTCGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTTGGATATGCCCGAAGT CAGTGACCCAACCGTAAGGAGGGAGCTGCCGAAGGTGGAGCCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCG TATCGGAAGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 19 Ba.cteroid.es stercoris

[0384] ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTATAGGCTTAACACATGCAAGTC GAGGGGCAGCATCATCAAAGCTTGCTTTGATGGATGGCGACCGGCGCACGGGTGAGTAAC ACGTATCCAACCTGCCGACAACTCTGGGATAGCCTTTCGAAAGAAAGATTAATACCGGAT GGCATAGTTTTCCCGCATGGGTTGACTATTAAAGAATTTCGGTTGTCGATGGGGATGCGT TCCATTAGGCAGTTGGCGGGGTAACGGCCCACCAAACCGACGATGGATAGGGGTTCTGAG AGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTG AGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGAAGGATGACTGCC CTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTTAGCCACGTGTGGCTTTTTGTAT GTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATC CGAGCGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGTTGTTAAGTCAGTTG T GAAAGT T T GC GGCT C AACC GT AAAAT T GC AGT T GAT AC T GGC GAC CT T GAGT GC AAC AG AGGTAGGCGGAATTCGTGGTGTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATT GCGAAGGCAGCTTACTGGATTGTAACTGACGCTGATGCTCGAAAGTGTGGGTATCAAACA GGAT T AGAT ACC CT GGT AGT CC AC AC AGT AAAC GAT GAAT AC T C GC T GT T GGC GAT AT AC TGTCAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGTGA AACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGA TACGCGAGGAACCTTACCCGGGCTTAAATTGCAACTGACGGAATCGGAAACGGTTCTTTC TTCGGACAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCT TAAGTGCCATAACGAGCGCAACCCTTATCGATAGTTACTAGCAGGTCATGCTGAGGACTC TATCGAGACTGCCGTCGTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCC CTTACGTCCGGGGCTACACACGTGTTACAATGGGGGGTACAGAAGGCAGCTACACGGCGA CGTGGTGCTAATCCCGAAAGCCTCTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCAT GAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGCGGTGAATACGTTCCCGGGCC TTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTACGTAACCGCGAG GAGCGTCCTAGGGTAAAACTGGTGATTGGGGCTAAGTCGTAACAAGGTAGCCGTACCGGA AGGTGCGGCTGGAACACCTCCTT SEQ ID No. 20 Bacteroides Stercoris ATGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCTACAGGCTTAACACATGCAAGTCGAGGGGCA GCATCATCAAAGCTTGCTTTGATGGATGGCGACCGGCGCACGGGTGAGTAACACGTATCCAACCTGCC GACAACACTGGGATAGCCTTTCGAAAGAAAGATTAATACYGGATGGCATAGTTTTCCCGCATGGGATA ATTATTAAAGAATTTCGGTTGTCGATGGGGATGCGTTCCATTAGGCAGTTGGCGGGGTAACGGCCCAC CAAACCWACGATGGATAGGGGTTCTGAGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAAC TCCTACGGGAGGCAGCAGTGAGGAATATTGGTCAATGGACGAGAGTCTGAACCAGCCAAGTAGCGTGA AGGATGACTGCCCTATGGGTTGTAAACTTCTTTTATACGGGAATAAAGTTAGCCACGTGTGGYTTTTT GTATGTACCGTATGAATAAGGATCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGATCCGAG CGTTATCCGGATTTATTGGGTTTAAAGGGAGCGTAGGCGGGTTGTTAAGTCAGTTGTGAAAGTTTGCG GCTCAACCGTAAAATTGCAGTTGATACTGGCGACCTTGAGTGCAACAGAGGTAGGCGGAATTCGTGGT GTAGCGGTGAAATGCTTAGATATCACGAAGAACTCCGATTGCGAAGGCAGCTTACTGGATTGTAACTG ACGCTGATGCTCGAAAGTGTGGGTATCAAACAGGATTAGATACCCTGGTAGTCCACACAGTAAACGAT GAATACTCGCTGTTGGCGATATACRGTCAGCGGCCAAGCGAAAGCATTAAGTATTCCACCTGGGGAGT ACGCCGGCAACGGTGAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAA TTCGATGATACGCGAGGAACCTTACCCGGGCTTAAATTGCAACTGACTGAACCGGAAACGGTTCTTTC TTCGGACAGTTGTGAAGGTGCTGCATGGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCC ATAACGAGCGCAACCCTTATCGATAGTTACTAGCAGGTCATGCTGAGGACTCTATTGAGACTGCCGTC GTAAGATGTGAGGAAGGTGGGGATGACGTCAAATCAGCACGGCCCTTACGTCCGGGGCTACACACGTG TTACAATGGGGGGTACAGAAGGCAGCTACACGGCGACGTGGTGCTAATCCCTAAAGCCTCTCTCAGTT CGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGCATCAGCCACGGCGC GGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGAAAGCCGGGGGTACCTGAAGTA CGTAACCGCGAGGAGCGTCCTAGGGTAAAACTGGTGATTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTT SEQ ID NO 21 Roseburia faecis

[0385] ATGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCG AACGAAGCACTCTATTTGATTTTCTTCGGAAATGAAGATTTTGTGACTGAGTGGCGGACG GGT GAGT AACGC GT GGGT AACCT GCCT CAT ACAGGGGGAT AACAGT T GGAAACGACT GCT AATACCGCATAAGCGCACAGGATCGCATGATCCGGTGTGAAAAACTCCGGTGGTATGGGA TGGACCCGCGTCTGATTAGCCAGTTGGCAGGGTAACGGCCTACCAAAGCGACGATCAGTA GCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGG AGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAG CGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAGAATGACGGTACCTGA CTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAGCGTT ATCCGGATTTACTGGGTGTAAAGGGAGCGCAGGCGGTGCGGCAAGTCTGATGTGAAAGCC CGGGGCTCAACCCCGGTACTGCATTGGAAACTGTCGTACTAGAGTGTCGGAGGGGTAAGT GGAAT T CC T AGT GT AGC GGT GAAAT GC GT AGAT AT T AGGAGGAAC ACC AGT GGC GAAGGC GGCTTACTGGACGATAACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGA TACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGAGCATTGCTCTTCG GT GC C GC AGC AAAC GC AAT AAGT AT T C C ACC T GGGGAGT AC GT T C GC AAGAAT GAAAC T C AAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGC GAAGAACCTTACCAAGTCTTGACATCCCGATGACAAGCTATGTAATGTAGCCTCTCTTCG GAGCATCGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA AGTCCCGCAACGAGCGCAACCCCTGTTCTTAGTAGCCAGCGGTTCGGCCGGGCACTCTAG GGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTT ATGACTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGGAGCCGTGAGGC CGAGCAAATCTCAAAAATAACGTCTCAGTTCGGACTGTAGTCTGCAACCCGACTACACGA AGCTGGAATCGCTAGTAATCGCAGATCAGAATGCTGCGGTGAATACGTTCCCGGGTCTTG TACACACCGCCCGTCACACCATGGGAGTTGGAAATGCCCGAAGTCAGTGACCCAACCGCA AGGAGGGAGCTGCCGAAGGCAGGTTCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCGT ATCGGAAGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 22 Roseburia faecis

[0386] ATGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCG AACGAAGCACTCTATTTGATTTTCTTCGGAAATGAAGATTTTGTGACTGAGTGGCGGACG GGT GAGT AACGC GT GGGT AACCT GCCT CAT ACAGGGGGAT AACAGT T GGAAACGACT GCT AATACCGCATAAGCGCACAGGATCGCATGATCCGGTGTGAAAAACTCCGGTGGTATGGGA TGGACCCGCGTCTGATTAGCCAGTTGGCAGGGTAACGGCCTACCAAAGCGACGATCAGTA GCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGG AGGCAGCAGTGGGGAATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAG CGAAGAAGTATTTCGGTATGTAAAGCTCTATCAGCAGGGAAGAAGAATGACGGTACCTGA CTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACGTATGGTGCAAGCGTT ATCCGGATTTACTGGGTGTAAAGGGAGCGCAGGCGGTGCGGCAAGTCTGATGTGAAAGCC CGGGGCTCAACCCCGGTACTGCATTGGAAACTGTCGTACTAGAGTGTCGGAGGGGTAAGT GGAAT T CC T AGT GT AGC GGT GAAAT GC GT AGAT AT T AGGAGGAAC ACC AGT GGC GAAGGC GGCTTACTGGACGATAACTGACGCTGAGGCTCGAAAGCGTGGGGAGCAAACAGGATTAGA TACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGGGAGCATTGCTCTTCG GT GC C GC AGC AAAC GC AAT AAGT AT T C C ACC T GGGGAGT AC GT T C GC AAGAAT GAAAC T C AAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGC GAAGAACCTTACCAAGTCTTGACATCCCGATGACAGAGTATGTAATGTACTTTCTCTTCG GAGCATCGGTGACAGGTGGTGCATGGTTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTA AGTCCCGCAACGAGCGCAACCCCTGTTCTTAGTAGCCAGCGGTCCGGCCGGGCACTCTAG GGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTT ATGACTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGGAGCCGTGAGGC CGAGCAAATCTCAAAAATAACGTCTCAGTTCGGACTGTAGTCTGCAACCCGACTACACGA AGCTGGAATCGCTAGTAATCGCAGATCAGAATGCTGCGGTGAATACGTTCCCGGGTCTTG TACACACCGCCCGTCACACCATGGGAGTTGGAAATGCCCGAAGTCAGTGACCCAACCGCA AGGAGGGAGCTGCCGAAGGCAGGTTCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCGT ATCGGAAGGTGCGGCTGGATCACCTCCTTT SEQ ID No. 23 Roseburia faecis ATGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGTGCTTAACACATGCAAGTCGAACGAAGCACTCTAT TTGATTTCCTTCGGGATTGAAGATTTTGTGACTGAGTGGCGGACGGGTGAGTAACGCGTGGGTAACCTGCCTCAT ACAGGGGGATAACAGTTGGAAACGACTGCTAATACCGCATAAGCGCACRGGATYGCATGATYCGGTGYGAAAAAC TCCGGTGGTAYGRGATGGACCCGCGTCTGATTAGCCAGTTGGCAGGGTAACGGCCTACCAAAGCGACGATCAGTA GCCGACCTGAGAGGGTGACCGGCCACATTGGGACTGAGACACGGCCCAAACTCCTACGGGAGGCAGCAGTGGGGA ATATTGCACAATGGGGGAAACCCTGATGCAGCGACGCCGCGTGAGCGAAGAAGTATTTCGGTATGTAAAGCTCTA TCAGCAGGGAAGAAGAATGACGGTACCTGACTAAGAAGCACCGGCTAAATACGTGCCAGCAGCCGCGGTAATACG TATGGTGCAAGCGTTATCCGGATTTACTGGGTGTAAAGGGAGCGCAGGCGGTGCGGCAAGTCTGATGTGAAAGCC CGGGGCTCAACCCCGGTACTGCATTGGAAACTGTCGTACTAGAGTGTCGGAGGGGTAAGTGGAATTCCTAGTGTA GCGGTGAAATGCGTAGATATTAGGAGGAACACCAGTGGCGAAGGCGGCTTACTGGACGATAACTGACGCTGAGGC TCGAAAGCGTGGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCCGTAAACGATGAATACTAGGTGTCGGG GAGCATTGCTCTTCGGTGCCGCAGCAAACGCARTAAGTATTCCACCTGGGGAGTACGTTCGCAAGAATGAAACTC AAAGGAATTGACGGGGACCCGCACAAGCGGTGGAGCATGTGGTTTAATTCGAAGCAACGCGAAGAACCTTACCAA GTCTTGACATCCCGATGRCAGAGTATGTAATGTASYYTCTCYTCGGAGCATCGGTGACAGGTGGTGCATGGTTGT CGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCTGTTCTTAGTAGCCAGCGGTYC GGCCGGGCACTCTAGGGAGACTGCCAGGGATAACCTGGAGGAAGGCGGGGATGACGTCAAATCATCATGCCCCTT ATGACTTGGGCTACACACGTGCTACAATGGCGTAAACAAAGGGAAGCGGAGCCGTGAGGCCGAGCAAATCTCAAA AATAACGTCTCAGTTCGGACTGTAGTCTGCAACCCGACTACACGAAGCTGGAATCGCTAGTAATCGCAGATCAGA ATGCTGCGGTGAATACGTTCCCGGGTCTTGTACACACCGCCCGTCACACCATGGGAGTTGGAAATGCCCGAAGTC AGTGACCCAACCGCAAGGAGGGAGCTGCCGAAGGCAGGTTCGATAACTGGGGTGAAGTCGTAACAAGGTAGCCGT ATCGGAAGGTGCGGCTGGATCACCTCCTTT SEQ ID NO 24 Slackia isoflavoniconvertans

[0387] CGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGCGCCTAACACATGCAAGTCG AACGAGTAAGACGCCTTCGGGCGTGGATAGAGTGGCGAACGGGTGAGTAACACGTGACCA ACCTGCCCCCTCCTCCGGGACAACCTCGGGAAACCGAGGCTAATACCGGATACTCCGGGC CCCCCGCATGGGGGGCCCGGGAAAGCCCTGGCGGGAGGGGATGGGGTCGCGGCCCATCAG GTAGACGGCGGGGTAACGGCCCACCGTGCCTGCAACGGGTAGCCGGGCTGAGAGGCCGAT CGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGGAATTT TGCGCAATGGGGGCAACCCTGACGCAGCGACGCCGCGTGCGGGACGAAGTCATTCGTGAC GTAAACCGCTTTCAGCGAGGAAGAACCATGACGGTACTCGCAGAAGAAGCCCCGGCTAAC TACGTGCCAGCAGCCGCGGTAATACGTAGGGGGCGAGCGTTATCCGGAATCATTGGGCGT AAAGCGCGCGCAGGCGGGCTTTCAAGCGGCGGCGTCGAAGCCGGGGGCTCAACCCCCGGA AGCGCCCCGAACTGGAAGCCTCGGATGCGGCAGGGGGAGGCGGAATTCCCGGTGTAGCGG T GAAAT GC GCAGAT AT CGGGAAGAACACCGACGGC GAAGGCAGCCT OCT GGGCC GGCATC GACGCTGAGGCGCGAAAGCTGGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCCAGCC GTAAACGATGGACGCTAGGTGTGGGGGGATAGGTCCCTCCGTGCCGAAGCCAACGCATTA AGCGTCCCGCCTGGGGAGTACGGCCGCAAGGCTAAAACTCAAAGGAATTGACGGGGGCCC GCACAAGCAGCGGAGCATGTGGCTTAATTCGAAGCAACGCGAAGAACCTTACCAGGGCTT GACATATCGGTGAAGCCGGAGAGATCCGGTGGCCGAGAGGAGCCGATACAGGTGGTGCAT GGCTGTCGTCAGCTCGTGCCGTGAGGTGTTGGGTTAAGTCCCGCAACGAGCGCAACCCCC GCCGCGTGTTGCCAGCATTCAGTTGGGCACTCACGCGGGACTGCCGGCGTCAAGCCGGAG GAAGGCGGGGACGACGTCAAGTCATCATGCCCCTCATGCCCTGGGCCGCACACGTGCTAC AATGGCCGGCACAACGGGTTGCCACCCCGCGAGGGGGAGCGGATCCCCAAAGCCGGCCCC AGTTCGGATCGCAGGCTGCAACCCGCCTGCGTGAAGCCGGAGTTGCTAGTAATCGCGGAT CAGCACGCCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCACACCACCCGA GTCGTCTGCACCCGAAGCCGCCGGCCGAACCCCTCCGGGGGGCGGAGGCGTCGAAGGTGT GGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCGGCTGGATCA

[0388] SEQ ID NO. 25 Slackia isoflavoniconvertens CGGAGAGTTTGATCCTGGCTCAGGATGAACGCTGGCGGCGCGCCTAACACATGCAAGTCGAACGAGTAAGA CGCCTTCGGGCGTGGATAGAGTGGCGAACGGGTGAGTAACACGTGACCAACCTGCCCCCTCCTCCGGGACA ACCTCGGGAAACCGAGGCTAATACCGGATACTCCGGGCCCCCCGCATGGGRKGCCCGGGAAAGCCCTGRCG GGAGGGGATGGGGTCGCGGCCCATCAGGTAGACGGCGGGGTAACGGCCCACCGTGCCYRCWACGGGTAGCC GGGCTGAGAGGCCGATCGGCCACATTGGGACTGAGACACGGCCCAGACTCCTACGGGAGGCAGCAGTGGGG AATTTTGCGCAATGGGGGCAACCCTGACGCAGCGACGCCGCGTGCGGGACGAAGTCATTCGTGACGTAAAC CGCTTTCAGCGAGGAAGAACCATGACGGTACTCGCAGAAGAAGCCCCGGCTAACTACGTGCCAGCAGCCGC GGTAATACGTAGGGGGCGAGCGTTATCCGGAATCATTGGGCGTAAAGCGCGCGCAGGCGGGCTTTCAAGCG GCGGCGTCGAAGCCGGGGGCTCAACCCCCGGAAGCGCCCCGAACTGGAAGCCTCGGATGCGGCAGGGGGAG GCGGAATTCCCGGTGTAGCGGTGAAATGCGCAGATATCGGGAAGAACACCGACGGCGAAGGCAGCCTCCTG GGCCGGCATCGACGCTGAGGCGCGAAAGCTGGGGGAGCGAACAGGATTAGATACCCTGGTAGTCCCAGCCG TAAACGATGGACGCTAGGTGTGGGGGGAWMGRTCCCTCCGTGCCGAAGCCAACGCATTAAGCGTCCCGCCT GGGGAGTACGGCCGCAAGGCTAAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCAGCGGAGCATGTGGC TTAATTCGAAGCAACGCGAAGAACCTTACCAGGGCTTGACATATCGGTGAAGCCGGAGAGATCCGGTGGCC GAGAGGAGCCGATACAGGTGGTGCATGGCTGTCGTCAGCTCGTGCCGTGAGGTGTTGGGTTAAGTCCCGCA ACGAGCGCAACCCCCGCCGCGTGTTGCCAGCATTCAGTTGGGCACTCACGCGGGACTGCCGGCGTCAAGCC GGAGGAAGGCGGGGACGACGTCAAGTCATCATGCCCCTCATGCCCTGGGCCGCACACGTGCTACAATGGCC GGCACAACGGGTTGCCACCCCGCGAGGGGGAGCGGATCCCYAAAGCCGGCCCCAGTTCGGATCGCAGGCTG CAACCCGCCTGCGTGAAGCCGGAGTTGCTAGTAATCGCGGATCAGCACGCCGCGGTGAATACGTTCCCGGG CCTTGTACACACCGCCCGTCACACCACCCGAGTCGTCTGCACCCGAAGCCGCCGGCCGAACCCCTCCGGGG GGCGGAGGCGTCGAAGGTGTGGAGGGTGAGGGGGGTGAAGTCGTAACAAGGTAGCCGTACCGGAAGGTGCG GCTGGATCACCTCCTTT

[0389] SEQ ID NO. 26 Barnesiella intestinihominis CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCCTAACACATGCAAGTCGAGGGGCAGCGAAGAG GTAGCAATACCTTTGTCGGCGACCGGCGCACGGGTGAGTAACACGTATGCAATCCACCTGTAACAGGGGGATAAC CCGGAGAAATCCGGACTAATACCCCATAATATGGGCGCTCCGCATGGAGAGCCCATTAAAGAGAGCAATTTTGGT TACAGACGAGCATGCGCTCCATTAGCCAGTTGGCGGGGTAACGGCCCACCAAAGCGACGATGGATAGGGGTTCTG AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTC AATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTAAACCTCTTTTGTCGGA GAGTAAAGTACGCTACGTGTAGCGTATTGCAAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGCCG CGGTAATACGGAGGATGCAAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCACGCCAAGTCAGC GGTGAAATTTCCGGGCTCAACCCGGACTGTGCCGTTGAAACTGGCGAGCTAGAGTACACAAGAGGCAGGCGGAAT GCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCTAGGGTGAAACAG ACGCTGAGGCACGAAAGCGTGGGTATCGAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGAATACT AACTGTTTGCGATACAATGTAAGCGGTACAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACC TTACCCGGGCTCAAACGCAGGGGGAATATATATGAAAGTATATAGCTAGCAATAGTCACCTGCGAGGTGCTGCAT GGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTATCGACAGTTACTAA CGGGTGAAGCCGAGGACTCTGTCGAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCAAATCAGCAC GGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGAAGGCAGCCAGTCAGCAATGACGCGCGAA TCCCGAAAACCTGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGC ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGTACC TGAAGCATGCAACCGCAAGGAGCGTACGAAGGTAATACCGGTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTTT SEQ ID NO. 27 Barnesiella intestinihominis CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCCTAACACATGCAAGTCGAGGGGCAGCGGGGAG GTAGCAATACCTTTGCCGGCGACCGGCGCACGGGTGAGTAACACGTATGCAATCCACCTGTAACAGGGGGATAAC CCGGAGAAATCCGGACTAATACCCCATAATATGGGCGCTCCGCATGGAGAGTTCATTAAAGAGAGCAATTTTGGT TACAGACGAGCATGCGCTCCATTAGCCAGTTGGCGGGGTAACGGCCCACCAAGGCGACGATGGATAGGGGTTCTG AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTC AATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTAAACCTCTTTTGTCGGA GAGTAAAGTACGCTACGTGTAGCGTATTGCAAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGCCG CGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCACGCCAAGTCAGC GGTGAAATTTCCGGGCTCAACCCGGAGTGTGCCGTTGAAACTGGCGAGCTAGAGTACACAAGAGGCAGGCGGAAT GCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCTAGGGTGAAACAG ACGCTGAGGCACGAAAGCGTGGGTATCGAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGAATACT AACTGTTTGCGATACAATGTAAGCGGTACAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACC TTACCCGGGCTCAAACGCAGGGGGAATGTCGGTGAAAGCCGGCAGCTAGTAATAGTCACCTGCGAGGTGCTGCAT GGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTATCGACAGTTACTAA CGGGTGAAGCCGAGGACTCTGTCGAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCAAATCAGCAC GGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGAAGGCAGCCAGTCAGCAATGACGCGCGAA TCCCGAAAACCTGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGC ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGTACC TGAAGCATGCAACCGCAAGGAGCGTACGAAGGTAATACCGGTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTTT SEQ ID NO. 28 Barnesiella intestinihominis CGAAGAGTTTGATCCTGGCTCAGGATGAACGCTAGCGACAGGCCTAACACATGCAAGTCGAGGGGCAGCGGRGAG GTAGCAATACCTTTGCCGGCGACCGGCGCACGGGTGAGTAACACGTATGCAATCCACCTGTAACAGGGGGATAAC CCGGAGAAATCCGGACTAATACCCCATAATATGGGCKCTCCGCATGGAGGGCTCATTAAAGARAGCAATTTTGGT TACAGACGAGCATGCGCTCCATTAGCCAGTTGGCGGGGTAACGGCCCACCAAAGCGACGATGGATAGGGGTTCTG AGAGGAAGGTCCCCCACATTGGAACTGAGACACGGTCCAAACTCCTACGGGAGGCAGCAGTGAGGAATATTGGTC AATGGTCGGCAGACTGAACCAGCCAAGTCGCGTGAGGGAAGACGGCCCTACGGGTTGTAAACCTCTTTTGTCGGA GAGTAAAGTACGCTACGTGTAGYGTATTGCAAGTATCCGAAGAAAAAGCATCGGCTAACTCCGTGCCAGCAGCCG CGGTAATACGGAGGATGCGAGCGTTATCCGGATTTATTGGGTTTAAAGGGTGCGTAGGCGGCACGCCAAGTCAGC GGTGAAATTTTCGGGCTCAACCCGGAGTGTGCCGTTGAAACTGGCGAGCTAGAGTACACAAGAGGCAGGCGGAAT GCGTGGTGTAGCGGTGAAATGCATAGATATCACGCAGAACCCCGATTGCGAAGGCAGCCTGCTAGGGTGAAACAG ACGCTGAGGCACGAAAGCGTGGGTATCGAACAGGATTAGATACCCTGGTAGTCCACGCAGTAAACGATGAATACT AACTGTTTGCGATACAATGTAAGCGGTACAGCGAAAGCGTTAAGTATTCCACCTGGGGAGTACGCCGGCAACGGT GAAACTCAAAGGAATTGACGGGGGCCCGCACAAGCGGAGGAACATGTGGTTTAATTCGATGATACGCGAGGAACC TTACCCGGGCTCAAACGCAGGGGGAATGTCGGTGAAAGCCGGCAGCTAGTAATAGTCACCTGCGAGGTGCTGCAT GGTTGTCGTCAGCTCGTGCCGTGAGGTGTCGGCTTAAGTGCCATAACGAGCGCAACCCCTATCGACAGTTACTAA CGGGTGAAGCCGAGGACTCTGTCGAGACTGCCGGCGCAAGCCGCGAGGAAGGTGGGGATGACGTCAAATCAGCAC GGCCCTTACGTCCGGGGCGACACACGTGTTACAATGGCAGGTACAGAAGGCAGCCAGTCAGCAATGACGCGCGAA TCCCGAAAACCTGTCTCAGTTCGGATTGGAGTCTGCAACCCGACTCCATGAAGCTGGATTCGCTAGTAATCGCGC ATCAGCCATGGCGCGGTGAATACGTTCCCGGGCCTTGTACACACCGCCCGTCAAGCCATGGAAGCCGGGAGTACC TGAAGCATGCAACCGCAAGGAGCGTACGAAGGTAATACCGGTAACTGGGGCTAAGTCGTAACAAGGTAGCCGTAC CGGAAGGTGCGGCTGGAACACCTCCTTT

[0390] Residues are designated according to the IUPAC code

[0391] IUPAC nucleotide code Base

[0392] A Adenine

[0393] C Cytosine

[0394] G Guanine

[0395] T (or U) Thymine (or Uracil)

[0396] R A orG Y C or T

[0397] S G or C W A or T

[0398] K G or T M A or C

[0399] B C or G or T D A or G or T H A or C or T V A or C or G N any base. or - gap

Claims

1. Claims1. A composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae for use in the treatment or prevention of radiation induced gastrointestinal toxicities.

2. The composition of claim 1 wherein the composition is for use in the treatment or prevention of radiation enteritis.

3. The composition of claim 1 or 2 comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae and Prevotellaceae; Coriobacteriaceae, Christensenellaceae and Barnesiellaceae; Coriobacteriaceae, Prevotellaceae and Barnesiellaceae; or Christensenellaceae, Prevotellaceae and Barnesiellaceae.

4. The composition of claim 1 or 2 comprising isolated bacteria belonging to the family Coriobacteriaceae and Christensenellaceae; Coriobacteriaceae and Prevotellaceae; Coriobacteriaceae and Barnesiellaceae; Christensenellaceae and Prevotellaceae; Christensenellaceae and Barnesiellaceae; or Prevotellaceae and Barnesiellaceae.

5. The composition of claim 1 comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and Barnesiellaceae.

6. The composition of claim 1 or 2 comprising isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and / or Barnesiella.

7. The composition of claim 6 comprising isolated bacteria belonging to the genus Senegalimassilia, Christensenella and Prevotella; Senegalimassilia, Christensenella and Barnesiella; Senegalimassilia, Prevotella and Barnesiella; or Christensenella, Prevotella and Barnesiella8. The composition of claim 6 comprising isolated bacteria belonging to the genus Senegalimassilia and Christensenella; Senegalimassilia and Prevotella; Senegalimassilia and Barnesiella; Christensenella and Prevotella; Christensenella and Barnesiella; or Prevotella and Barnesiella.

9. The composition of claim 6 comprising isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and Barnesiella.

10. The composition of claim 1 or 2 comprising isolated bacteria selected from Christensenellaceae R-7 group sp., Senegalimassilia anaerobia, Prevotella copri and / or Barnesiella intestinihominis.

11. The composition of claim 10 comprising isolated bacteria selected from Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Prevotella copri; Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Barnesiella intestinihominis; Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis; or Christensenellaceae R-7 group sp., Prevotella copri and Barnesiella intestinihominis.

12. The composition of claim 10 comprising isolated bacteria selected from Christensenellaceae R-7 group sp. and Senegalimassilia anaerobia; Senegalimassilia anaerobia and Prevotella copri; Senegalimassilia anaerobia and Barnesiella intestinihominis; Christensenellaceae R-7 group sp. and Prevotella copri; Christensenellaceae R-7 group sp. and Barnesiella intestinihominis; or Prevotella copri and Barnesiella intestinihominis.

13. The composition of claim 10 comprising isolated bacteria selected from Christensenellaceae R-7 group sp., Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis.

14. The composition of claim 1 or 2 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and / or isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

15. The composition of claim 1 or 2 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7.

16. The composition of claim 1 or 2 comprising isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

17. The composition according to any preceding claim comprising one or more further bacteria.

18. The composition according to claim 17, wherein the further bacteria belong to the family Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae, Ruminococcaceae and / or Lachnospiraceae.

19. The composition according to claim 17, wherein the further bacteria belong to the genus Bifidobacterium, Eubacterium, Bacteroides, Ruminococcus and / or Roseburia20. The composition according to claim 17, wherein the further bacteria are selected from Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Eubacterium ventriosum, Bacteroides stercoris and / or Roseburia faecis bacteria.

21. The composition according to claim 17, wherein the further bacteria comprise Slackia isoflavoniconvertens.

22. The composition according to claims 17 to 21, wherein the one or more further bacteria are selected from Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae and / or Lachnospiraceae bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence selected from according to SEQ ID NO: 12 to 23.

23. The composition according to claim 22 further comprising Slackia isoflavoniconvertens bacteria comprising a 16S rDNA sequence having at least 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 24 or 25.

24. The composition according to any preceding claim, wherein said composition is formulated for oral or rectal administration.

25. The composition according to claim 24, wherein said composition is in the form of a capsule, tablet, gel or liquid.

26. The composition according to claim 25, wherein said composition is encapsulated in an enteric coating.

27. The composition according to any preceding claim, wherein the composition comprises live, attenuated or killed bacteria.

28. The composition according to any preceding claim, wherein the composition comprises bacterial spores.

29. The composition according to any of claims 1 to 28, wherein the composition is substantially free of bacterial spores.

30. The composition according to any preceding claim, wherein the composition comprises bacterial strains that originate from one or more human donor.

31. The composition according to any preceding claim, wherein the bacteria are lyophilized.

32. The composition according to any preceding claim, wherein the composition comprises at least about 1x103to 1x1013CFU of bacteria.

33. The composition according to any preceding claim, wherein the composition is administered prior to, concurrent with or after radiotherapy treatment.

34. A method for treating or preventing radiation induced Gl toxicities, comprising administering a composition comprising isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and / or Barnesiellaceae to a subject.

35. The method according to claim 34 wherein the radiation induced Gl toxicity is radiation enteritis.

36. The method according to claim 34 or 35 comprising administering isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae and Prevotellaceae; Coriobacteriaceae, Christensenellaceae and Barnesiellaceae; Coriobacteriaceae, Prevotellaceae and Barnesiellaceae; or Christensenellaceae, Prevotellaceae and Barnesiellaceae.

37. The method according to claim 34 or 35 comprising administering isolated bacteria belonging to the family Coriobacteriaceae and Christensenellaceae; Coriobacteriaceae and Prevotellaceae; Coriobacteriaceae and Barnesiellaceae; Christensenellaceae and Prevotellaceae; Christensenellaceae and Barnesiellaceae; or Prevotellaceae and Barnesiellaceae38. The method of claim 34 or 35 comprising administering isolated bacteria belonging to the family Coriobacteriaceae, Christensenellaceae, Prevotellaceae and Barnesiellaceae.

39. The method of claim 34 or 35 comprising administering isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and / or Barnesiella.

40. The method of claim 39 comprising administering isolated bacteria belonging to the genus Senegalimassilia, Christensenella and Prevotella; Senegalimassilia, Christensenella and Barnesiella; Senegalimassilia, Prevotella and Barnesiella; or Christensenella, Prevotella and Barnesiella41. The method of claim 39 comprising administering isolated bacteria belonging to the genus Senegalimassilia and Christensenella; Senegalimassilia and Prevotella; Senegalimassilia and Barnesiella; Christensenella and Prevotella; Christensenella and Barnesiella; or Prevotella and Barnesiella.

42. The method of claim 39 comprising administering isolated bacteria belonging to the genus Senegalimassilia, Christensenella, Prevotella and Barnesiella.

43. The method of claim 34 or 35 comprising administering isolated bacteria selected from Christensenellaceae R-7 group sp., Senegalimassilia anaerobia, Prevotella copri and / or Barnesiella intestinihominis.

44. The method of claim 43 comprising administering isolated bacteria selected from Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Prevotella copri; Senegalimassilia anaerobia, Christensenellaceae R-7 group sp. and Barnesiella intestinihominis; Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis; or Christensenellaceae R-7 group sp. Prevotella copri and Barnesiella intestinihominis.

45. The method of claim 43 comprising administering isolated bacteria selected from Christensenellaceae R-7 group sp. and Senegalimassilia anaerobia; Senegalimassilia anaerobia and Prevotella copri; Senegalimassilia anaerobia and Barnesiella intestinihominis; Christensenellaceae R-7 group sp. and Prevotella copri; Christensenellaceae R-7 group sp. and Barnesiella intestinihominis; or Prevotella copri and Barnesiella intestinihominis.

46. The method of claim 43 comprising administering isolated bacteria selected from Christensenellaceae R-7 group sp., Senegalimassilia anaerobia, Prevotella copri and Barnesiella intestinihominis.

47. The method of claim 34 or 35 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising the 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, isolated bacteria comprising the 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and / or isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

48. The method of claim 34 or 35 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5 and isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7.

49. The method of claim 34 or 35 comprising administering isolated bacteria comprising a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 1 or 5, isolated bacteria comprising the 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 2, 6 or 7, isolated bacteria comprising the 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 3, 8, 9 or 10 and isolated bacteria comprising the 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 4, 11, 26, 27 or 28.

50. The method according to any of claims 34 to 49 comprising administering one or more further bacteria.

51. The method according to claim 50, wherein the further bacteria belong to the family Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae, Ruminococcaceae and / or Lachnospiraceae.

52. The method according to claim 51, wherein the further bacteria belong to the genus Bifidobacterium, Eubacterium, Bacteroides, Ruminococcus and / or Roseburia.

53. The method according to claim 52, wherein the further bacteria are Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Eubacterium ventriosum, Bacteroides stercoris and / or Roseburia faecis bacteria.

54. The method according to claim 50, wherein the further bacteria comprise Slackia isoflavoniconverten.

55. The method according to any of claims 50 to 54, wherein the one or more further bacteria are selected from Bifidobacteriaceae, Eubacteriaceae, Bacteroidaceae and / or Lachnospiraceae bacteria wherein the bacteria comprise a 16S rDNA sequence having at least 80%, 85%, 90%, 95% or 98.7% sequence identity with a nucleic acid sequence selected from SEQ ID NO: 12 to 23.

56. The method according to claim 55 further comprising administering Slackia isoflavoniconverten bacteria comprising a 16S rDNA sequence having at least 98.7% sequence identity with the nucleic acid sequence according to SEQ ID NO: 24 or 25.

57. The method according to any of claims 34 to 56, wherein said composition is formulated for oral or rectal administration.

58. The method according to claim 57, wherein said composition is in the form of a capsule, tablet, gel or liquid.

59. The method according to claim 58, wherein said composition is encapsulated in an enteric coating.

60. The method according to any of claims 34 to 59, wherein the composition comprises live, attenuated or killed bacteria.

61. The method according to any of claims 34 to 60, wherein the composition comprises bacterial spores.

62. The method according to any of claims 34 to 60, wherein the composition is substantially free of bacterial spores.

63. The method according to any of claims 34 to 62, wherein the composition comprises bacterial strains that originate from one or more human donor.

64. The method according to any of claims 34 to 63, wherein the bacteria are lyophilized.

65. The administering according to any of claims 34 to 64, wherein the composition comprises at least about 1x103to 1x1013CFU of bacteria.

66. The method according to of claims 34 to 65, wherein the composition is administered prior to, concurrent with or after radiotherapy treatment.

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