EP4003380A1 - Execalibacterium prausnitzii- und christensenella-bakterienstämme zur behandlung und vorbeugung von darmentzündungen - Google Patents

Execalibacterium prausnitzii- und christensenella-bakterienstämme zur behandlung und vorbeugung von darmentzündungen

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Publication number
EP4003380A1
EP4003380A1 EP20742750.1A EP20742750A EP4003380A1 EP 4003380 A1 EP4003380 A1 EP 4003380A1 EP 20742750 A EP20742750 A EP 20742750A EP 4003380 A1 EP4003380 A1 EP 4003380A1
Authority
EP
European Patent Office
Prior art keywords
composition
bacterial strain
christensenella
group
use according
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP20742750.1A
Other languages
English (en)
French (fr)
Inventor
Philippe Langella
Patrizia Brigidi
Rebeca MARTIN ROSIQUE
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Institut National de Recherche pour lAgriculture lAlimentation et lEnvironnement
Universita di Bologna
Original Assignee
Institut National de Recherche pour lAgriculture lAlimentation et lEnvironnement
Universita di Bologna
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Institut National de Recherche pour lAgriculture lAlimentation et lEnvironnement, Universita di Bologna filed Critical Institut National de Recherche pour lAgriculture lAlimentation et lEnvironnement
Publication of EP4003380A1 publication Critical patent/EP4003380A1/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
    • A61K2035/115—Probiotics

Definitions

  • the present invention relates to a composition for its use in the treatment and / or prevention of inflammatory gastrointestinal diseases in an individual, in particular inflammatory bowel conditions.
  • composition comprising particular bacterial strains, and / or their supernatants, for its use in the treatment and / or prevention of inflammatory gastrointestinal diseases in an individual, in particular inflammatory bowel disorders.
  • Inflammation is a natural biological process, which is a normal part of the response to injury or infection and helps protect the body against internal or external damage.
  • An inflammatory bowel disease is a group of disorders characterized by chronic and recurrent inflammation of the gastrointestinal tract. The most common form of this group is Crohn's disease.
  • the pathogenesis involves an inappropriate and continuous activation of the mucosal immune system brought about by the presence of the intestinal microbiota in a genetically predisposed patient.
  • the ability to modulate the immune response of Christensenella, and in particular of the bacterial strains Christensenella minuta and Christensenella timonensis was tested in vitro.
  • the inventors have determined the synergistic anti-inflammatory properties resulting from the implementation of association between a strain of Christensenella with a strain of Faecalibacterium prausnitzii, a well-known new generation probiotic (NGP).
  • NTP new generation probiotic
  • the present invention aims to provide a composition for its use in the treatment and / or prevention of an inflammatory gastrointestinal disease in an individual, the composition comprising, in a physiologically acceptable medium, at least a first bacterial strain of the Faecalibacterium prausnitzii species, and a second bacterial strain selected from the group consisting of Christensenella minuta, Christensenella timonensis, and / or their supernatants.
  • a pharmaceutical composition comprising, in a physiologically acceptable medium, these two strains and / or their supernatants is also targeted.
  • the objective of the present invention is to describe new substances, in particular probiotics and / or probiotic culture supernatants, and compositions for the treatment and / or prevention of inflammatory gastrointestinal diseases in an individual, by particularly inflammatory bowel disease in an individual.
  • prevention denote the reduction to a lesser degree of the risk or the probability of occurrence of a given phenomenon, that is to say, in the present invention.
  • invention gastrointestinal inflammation, in particular intestinal inflammation.
  • the terms “treating” and “treatment” associated with an inflammatory gastrointestinal disease denote a reduction, or even an interruption, of said inflammatory gastrointestinal disease.
  • the present invention is based on the discovery by the inventors of the capacity of certain Christensenella bacteria to improve the immunomodulatory properties of a strain of the species Faecalibacterium prausnitzii.
  • the simultaneous use of a first bacterial strain Faecalibacterium prausnitzii, or of a supernatant thereof, and of a second bacterial strain chosen from the group consisting of Christensenella minuta, Christensenella timonensis and their mixtures, or a supernatant thereof makes it possible to obtain anti-inflammatory results superior to the simple sum of the combined effects of these strains, or of their supernatant (s), used separately.
  • the present invention relates to a composition for its use in the treatment and / or prevention of an inflammatory gastrointestinal disease in an individual, the composition comprising, in a physiologically acceptable medium, at least:
  • the first bacterial strain is present in the composition in a living, inactive and / or dead form, preferably in a living form.
  • the second bacterial strain is present in the composition in a living, inactive and / or dead form, preferably in a living form.
  • the composition comprises at least:
  • the first bacterial of the Faecalibacterium prausnitzii species is strain A2-165, deposited in the German Collection of Microorganisms and Cell Cultures under number DSM-17677 in 1996.
  • the second bacterial strain is chosen from the group consisting of Christensenella minuta DSMZ 22607, Christensenella timonensis DSMZ 102800 and mixtures thereof.
  • An individual according to the present invention can in particular be a mammal, more particularly a human being.
  • the composition is used in an individual whose genus Christensenella represents at least 0.01% by number of the total of the bacterial genera of his intestinal microbiota.
  • inflammatory gastrointestinal disease may be inflammatory bowel disease, more particularly colonic inflammatory bowel disease.
  • Said colonic inflammatory bowel disease can in particular be selected from the group consisting of Crohn's disease, ulcerative colitis and pouchitis, in particular from the group consisting of Crohn's disease and ulcerative colitis. hemorrhagic.
  • the composition according to the invention is suitable for administration by the oral route.
  • the composition according to the invention can thus be in the form of powder or granules, of a food product, of a drink, of a pharmaceutical product, of a nutraceutical, of a food additive, of a food supplement. , a dairy product, a capsule or a capsule. More particularly, the composition according to the invention can be included in a food supplement.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising, in a physiologically acceptable medium, at least:
  • FIG 1 shows the production of interleukin-8 (IL-8) (in pg / mL) (ordinate) in HT-29 cells stimulated by (from left to right) TNF- ⁇ alone (YBHI mucin) or in the presence of the strains C. minuta DSMZ 22607 (C. minuta), C. timonensis DSMZ 102800 (C. timonensis), F. prausnitzii A2-165 (F. prausnitzii), C. minuta DSMZ 22607 + F. prausnitzii A2-165 (C. minuta + F. prausnitzii) and C. timonensis DSMZ 102800 + F. prausnitzii A2-165 (C. timonensis + F. prausnitzii) (abscissa).
  • IL-8 interleukin-8
  • the inventors have carried out in-depth work in order to identify the capacity of a composition
  • a composition comprising a first bacterial strain of the species Faecalibacterium prausnitzii, and / or a culture supernatant of this first strain, and a second bacterial strain chosen from the group consisting of Christensenella minuta, Christensenella timonensis and their mixtures, and / or a culture supernatant of this second strain, to treat and / or prevent inflammatory gastrointestinal diseases in an individual, in particular inflammatory bowel diseases.
  • the inventors have unexpectedly determined that a composition according to the invention has the capacity to reduce gastrointestinal inflammation, in particular intestinal inflammation, in an individual.
  • the composition according to the invention can, in particular, reduce the concentration of pro-inflammatory molecules, such as interleukin 8 (IL-8).
  • IL-8 interleukin 8
  • a bacterial strain of Christensenella in particular one or more of the Christensenella timonensis and Christensenella minuta strain (s), or their supernatant
  • Faecalibacterium prausnitzii in particular the reference strain A2-165, or with its supernatant
  • Faecalibacterium prausnitzii makes up about 5% of the fecal microbiota in healthy adults (Hold, Schwiertz et al., Appl Environ Microbiol. 2003 Jul; 69 (7): 4320-4).
  • the importance of this bacterium is recognized around the world, especially as a player in intestinal health in humans.
  • the relative abundance of F. prausnitzii may also serve as an indicator or biomarker of gut health in adults.
  • F. prausnitzii have been shown to be lower in the faeces of individuals suffering from intestinal and metabolic disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), cancer. colorectal (CRC), obesity and celiac disease (Balamurugan, Rajendiran et al. J Gastroenterol Hepatol. 2008 Aug; 23 (8 Pt 1): 1298-1303, Sokol, Pigneur et al. Proc Natl Acad Sci US A. 2008 Oct 28; 105 (43): 16731-6; Neish Gastroenterology. 2009 Jan; 136 (l): 65-80; De Palma, Nadal et al. BMC Microbiol.
  • F. prausnitzii implemented in a live form, exhibits anti-inflammatory effects in vitro and in vivo, which suggests that this bacterium could contribute to homeostasis in a healthy intestine.
  • Sokol, Pigneur et al. Proc Natl Acad Sci US A. 2008 Oct 28; 105 (43): 16731-6 Christensenella is an anaerobic bacterium and its culture requires special equipment and know-how.
  • applications WO2018 / 162738 and WO2018 / 162726 teach that the use of particular bacteria of Christensenella, belonging to species defined as being specifically distant from those of the genera Christensenella minuta and Christensenella timonensis, make it possible in particular to fight against overweight and obesity, by intervening for example on the presence of visceral fat and on intestinal permeability.
  • the inventors have surprisingly determined the ability of strains of Christensenella, and in particular of their supernatant, to increase the anti-inflammatory properties of a strain of Faecalibacterium prausnitzii, and in particular of its supernatant.
  • the inventors have demonstrated the existence of a synergistic effect of a combination of a strain of Christensenella minuta and / or of Christensenella timonensis (or of a culture supernatant of such strains) and of a strain of Faecalibacterium prausnitzii (or a supernatant of this strain) for the prevention and / or treatment of gastrointestinal inflammation.
  • the term “individual” as used in the present text preferably designates a mammal, including a non-human mammal, and more particularly a human being.
  • physiologically acceptable medium denote a medium which is compatible with the organism of the individual to which said composition is to be administered. It could be, for example, a non-toxic solvent such as water. In particular, said medium is compatible with oral administration.
  • a composition according to the invention is preferably suitable for administration by the oral route.
  • microbiota is meant all the microorganisms that have colonized an individual and with which he cohabits: bacteria for the most part, but also viruses, fungi, yeasts and protozoa.
  • the composition of the microbiota differs depending on the colonized surfaces: we thus distinguish the skin microbiota, the vaginal microbiota, the urinary microbiota, the respiratory microbiota, the ENT microbiota (otorhinolaryngology) and the intestinal microbiota, formerly called the intestinal flora, by far the most important with its 100,000 billion germs.
  • intestinal microbiota is meant all the microorganisms, in particular bacteria, which inhabit the intestine of a given individual.
  • BMI Body Mass Index
  • WHO World Health Organization
  • composition according to the invention relates to a composition for its use in the treatment and / or prevention of inflammatory gastrointestinal disease in an individual, the composition comprising, in a physiologically acceptable medium, at least:
  • the individual defined according to the invention is not overweight, i.e. has a body mass index (BMI) of less than 25.
  • BMI body mass index
  • BMI less than 25 denotes a BMI strictly less than 25, more particularly a BMI less than or equal to 24.99.
  • said individual may have a BMI of less than 25 and greater than or equal to 18.5.
  • the composition is used in an individual who is not deficient in Christensenella in the intestinal microbiota.
  • non-deficient in Christensenella in the intestinal microbiota, within the meaning of the present invention, is meant an individual whose bacteria of the genus Christensenella in his intestinal microbiota represent at least 0.01% by number of the total of the bacterial genera detected in his. intestinal microbiota, in particular at least 0.1% by number, and in particular at least 0.5% by number of the total bacterial genera detected in its intestinal microbiota.
  • the abundance of Christensenella can, for example, be measured by a Fish sequencing test, or by qPCR or by meta-analysis, well known to those skilled in the art.
  • the first bacterial strain of the species Faecalibacterium prausnitzii and / or the second bacterial strain as defined according to the invention can be independently implemented in a living, semi-active, inactivated or dead form.
  • a bacterial strain in a semi-active form is a microorganism whose ability to proliferate is reduced, temporarily or permanently.
  • the term “semi-active” thus designates a bacterium with low physiological activity. This activity can be measured by an exponential growth phase or a longer generation time, a slowed metabolism or an incomplete physiological response to changes in the environment, for example. In some extreme cases, the number of bacteria may be reduced since they can no longer resist changes in the environment.
  • an “inactivated” bacterial strain is a bacterial strain which is no longer capable, temporarily or permanently, of proliferating.
  • a “dead” bacterial strain is a bacterial strain which is no longer capable, definitively, of proliferating.
  • Dead or inactivated bacterial strains may have intact or ruptured cell membranes.
  • the term “inactivated” also designates the extracts and lysates of bacterial strains obtained as detailed above.
  • Obtaining dead or inactivated bacterial strains can be carried out by any method known to those skilled in the art.
  • An inactivated bacterial strain suitable for the invention can be prepared by irradiation, thermal inactivation or lyophilization of a preparation of bacterial strain. These methods are known to those skilled in the art.
  • the inactivation of bacterial strains by irradiation can include the use of gamma rays, X-rays or UV exposure.
  • the type of radiation, the intensity, the dose and the exposure time are adjusted by those skilled in the art depending on the quantity and nature of the bacterial strains to be inactivated.
  • Inactivation by lyophilization can be carried out by any method known in the field.
  • bacterial strains inactivated by lyophilization can be returned to culture.
  • a bacterial strain according to the invention can be used in whole form, that is to say essentially in its native form, or in the form of extracts or lysates comprising fractions and / or metabolites of this microorganism. Such a lysate can in particular be prepared as indicated below.
  • a lysate in accordance with the invention can comprise all or part of the fractionated elements and / or of the metabolites resulting from the lysis of the bacterial strain.
  • a lysate within the meaning of the invention denotes the product obtained at the end of the destruction or dissolution of biological cells by a phenomenon of cell lysis causing the release of the intracellular biological constituents naturally contained in the cells of the bacterial strain considered.
  • lysate is used interchangeably to denote the whole of the lysate obtained by lysis of the bacterial strain concerned or only a fraction thereof.
  • the terms “entire lysate” are used to designate more precisely the entire lysate obtained by lysis of the bacterial strain concerned.
  • the lysate used is therefore formed in all or part of the intracellular biological constituents and of the constituents of the cell walls and membranes.
  • a lysate used for the invention is the entire lysate obtained by lysis of the bacterial strain concerned.
  • This cell lysis can be carried out using different technologies, such as, for example, thermal shock, ultrasound, osmotic shock, or under mechanical stress, such as by centrifugation.
  • a culture supernatant of the first bacterial strain as defined above and / or a culture supernatant of the second bacterial strain as defined above can be used in a composition according to the invention.
  • the term “culture supernatant” denotes the culture medium in which the bacterial strains have resided during their culture, or extracellular medium.
  • the composition according to the invention comprises at least one culture supernatant of a bacterial strain of the species Faecalibacterium prausnitzii. According to one embodiment, the composition according to the invention comprises at least one bacterial strain of the species Faecalibacterium prausnitzii.
  • the composition according to the invention comprises at least one bacterial strain of the species Faecalibacterium prausnitzii and at least one culture supernatant of a bacterial strain of the species Faecalibacterium prausnitzii.
  • the bacterial strain of the species Faecalibacterium prausnitzii is a strain of the species F. prausnitzii having anti-inflammatory properties.
  • the bacterial strain of the species Faecalibacterium prausnitzii is the reference strain A2-165.
  • the composition according to the invention comprises a culture supernatant of at least one bacterial strain chosen from the group consisting of Christensenella timonensis, Christensenella minuta and / or mixtures thereof.
  • the composition according to the invention comprises at least one bacterial strain chosen from the group consisting of Christensenella timonensis, Christensenella minuta and / or their mixtures and a culture supernatant of at least one bacterial strain chosen from the group consisting of Christensenella timonensis, Christensenella minuta and / or mixtures thereof.
  • the composition comprises at least:
  • a composition of the invention is suitable for the administration of a daily dose representing from 10 7 to 10 11 colony-forming units (cfu) of at least one bacterial strain of the species Faecalibacterium prausnitzii, preferably a daily dose equivalent to 10 9 cfu.
  • a composition of the invention is suitable for the administration of a daily dose representing from 10 7 to 10 11 colony-forming units (cfu) of at least one bacterial strain chosen from the group consisting of Christensenella timonensis, Christensenella minuta and / or their mixtures, preferably a daily dose equivalent to 10 9 cfu.
  • a daily dose representing from 10 7 to 10 11 colony-forming units (cfu) of at least one bacterial strain chosen from the group consisting of Christensenella timonensis, Christensenella minuta and / or their mixtures, preferably a daily dose equivalent to 10 9 cfu.
  • a composition according to the invention can in particular comprise, independently, a content of between 0.1% and 99.0%. in weight, in particular between 5.0% and 90.0% by weight, in particular from 25 to 70% by weight and more particularly from 30 to 50% by weight, relative to the total weight of the composition.
  • a composition according to any one of the aforementioned embodiments can independently comprise a content of between 0.1% and 99.0% by weight, in particular between 5.0% and 90.0% by weight, for example between 10.0% and 90.0% by weight; in particular from 25 to 70% by weight and more particularly from 30 to 50% by weight, of supernatant of a first bacterial strain or of a second bacterial strain as defined above, relative to the total weight of the composition.
  • composition according to the invention is a pharmaceutical composition.
  • composition according to the invention is used in the treatment and / or prevention of an inflammatory gastrointestinal disease in an individual, more particularly a human being.
  • an inflammatory gastrointestinal disease is, in particular, an inflammatory bowel disease, more particularly an inflammatory bowel disease of the colon.
  • Said colonic inflammatory bowel disease can, in particular, be chosen from the group consisting of Crohn's disease (CD), ulcerative colitis (UC) and pouchitis, in particular Crohn's disease and ulcerative colitis.
  • CD Crohn's disease
  • UC ulcerative colitis
  • pouchitis in particular Crohn's disease and ulcerative colitis.
  • Crohn's disease and ulcerative colitis are two diseases characterized by inflammation of the lining of part of the digestive tract, linked to an overactive digestive immune system.
  • inflammatory bowel disorders in particular colic, more particularly Crohn's disease (CD), ulcerative colitis (UC) and pouchitis, are diseases predominantly affecting young adults, ie between 20 and 30 years old, and which evolve in spurts interspersed with periods of remission. These diseases can affect the entire digestive tract, from the mouth to the anus.
  • Crohn's disease is meant an inflammatory gastrointestinal disease which can affect the entire digestive tract. Crohn's disease, of unknown cause, is characterized by inflammation most often found in the ileum, colon and anus, which is of multifactorial origin, involving among other things a genetic component and the microbiome. Crohn's disease typically progresses in flare-ups spaced by so-called remission phases, asymptomatic. Digestive signs are most often diarrhea, abdominal pain or proctological lesion. Diagnosis of Crohn's disease requires esogastric fibroscopy and colonoscopy with biopsies. Crohn's disease can also be detected thanks to a video-capsule, this one allowing to visualize the intestines and more particularly the small intestine.
  • ulcerative colitis is meant a chronic inflammatory disease of the intestine which affects the distal end of the digestive tract, i.e. the colon and the rectum. It is characterized by continuous lesions, most often superficial, which begin in the rectum and can extend over the entire colon without ever reaching other segments of the digestive tract. It evolves in spurts interspersed with periods of remissions (calm periods without symptoms).
  • ileal reservoir obtained after a surgeon has performed an anastomosis between two parts of the intestines, i.e. the ileum and the anus. It primarily concerns patients suffering from ulcerative colitis, and having undergone total coloprotectomy.
  • a composition according to the present invention is in particular intended for the digestive tract, in particular the intestine.
  • composition according to the invention may be suitable for oral or rectal administration.
  • a composition of the invention is an oral composition, that is, it is suitable for oral administration to an individual.
  • Such a composition can be in the form of a suspension, a tablet, a pill, a capsule, a granule or a powder.
  • composition according to the invention for the oral route can be chosen from the group consisting of a food product, a drink, a pharmaceutical product, a nutraceutical, a food additive, a food supplement or a dairy product, and is, in particular , a food supplement.
  • a composition according to the present invention is a food supplement.
  • a dietary supplement for oral administration may be present in capsules, hard capsules, soft capsules, tablets, sugar-coated tablets, pills, pastes, lozenges, gums, drinkable solutions or emulsions, syrup or gel.
  • a composition according to the present invention intended for oral administration, can be provided with a coating resistant to gastric juice, in order to ensure that the bacterial strain of the present invention included in said composition can pass through the damaged stomach. The release of the bacterial strain may thus occur for the first time in the upper intestinal tract.
  • a food supplement according to the present invention may further comprise a sweetener, a stabilizer, an antioxidant, an additive, a flavoring agent and / or a colorant.
  • the formulation thereof is carried out by means of the usual processes for producing sugar-coated tablets, hard capsules, gels, controlled release hydrogels, emulsions, tablets or capsules.
  • a composition according to the present invention can also be in the form of a nutritional composition.
  • a nutritional composition according to the present invention is in the form of yogurt, cereal bar, breakfast cereal, dessert, frozen food, soup, pet food, liquid suspension, a powder, tablet, gum or candy.
  • composition containing the bacterial strain of the invention is administered intrarectally.
  • composition according to the invention administered rectally can be in the form of a suppository, an enema or a foam.
  • a composition according to the invention can also comprise at least one ingredient chosen from: antioxidants, fish oils, DHA, EPA, vitamins, minerals, phytonutrients, a protein, a lipid, probiotics and combinations of these.
  • the HT-29 (ATCC HTB-38) cell line (LGC-Standars) is cultured in Dulbecco's Modified Eagle's Minimal Essential Medium (DMEM) (Sigma-Aldrich) supplemented with 10% (w / v) serum heat-inactivated fetal bovine (FBS) (GibcoBRL, Eragny, France) and penicillin G / streptomycin (5000 IU / mL, 5000 pg / ml) (Sigma-Aldrich).
  • DMEM Dulbecco's Modified Eagle's Minimal Essential Medium
  • FBS serum heat-inactivated fetal bovine
  • penicillin G / streptomycin 5000 IU / mL, 5000 pg / ml
  • the single cultures and the co-cultures composed of the combinations between the listed strains are prepared at time 0. At 24 hours, the bacterial samples are centrifuged for 10 minutes at 6000 rpm. The supernatants thus obtained are stored at -80 ° C. in order to continue the analysis of their immunomodulatory properties in vitro.
  • Anti-inflammatory tests are carried out according to the procedure described by Kechaou et al. , 2012 (Kechaou N et a /.: Appl Environ Microbiol 2012, 79: 1491-1499). Specifically, 50,000 HeLa or HT-29 cells per well are seeded in 24-well culture plates (Nunc). Twenty-four hours before the bacterial contact, the culture medium is replaced by a medium containing 5% FBS. The experiments are undertaken on the 7th day after seeding, while the cells are at confluence (1.83 ⁇ 10 6 cells / well). Twenty-four hours before the bacterial co-culture (day 6), the culture medium is replaced with a medium containing 5% heat inactivated FBS and 1% glutamine.
  • the reference strain F. prausnitzii A2-165 is well known for its immunomodulatory properties and more particularly for its anti-inflammatory effects.
  • IL-8 a pro-inflammatory cytokine induced by TNF- ⁇ stimulation in HT-29 epithelial cells.
  • the inventors observed that the two strains are capable of blocking the production of IL-8 in the same way as the positive control (F. prausnitzii A2-165) (FIG. 1).
  • C. minuta DSMZ 22607 and C. timonensis DSMZ 102800 increase the anti-inflammatory properties of the F. prausnitzii A2-165 strain in vitro.
  • co-cultures with F. prausnitzii A2-165 were performed.
  • C. minuta DSMZ 22607 and C. timonensis DSMZ 102800 advantageously, and quite unexpectedly, synergistically increase the anti-inflammatory properties of the strain F. prausnitzii A2-165 in a manner statistically significant.

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EP20742750.1A 2019-07-24 2020-07-23 Execalibacterium prausnitzii- und christensenella-bakterienstämme zur behandlung und vorbeugung von darmentzündungen Withdrawn EP4003380A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR1908385A FR3099053B1 (fr) 2019-07-24 2019-07-24 Souches bacteriennes pour le traitement et la prevention d’une inflammation gastro-intestinale
PCT/EP2020/070830 WO2021013944A1 (fr) 2019-07-24 2020-07-23 Souches bacteriennes de faecalibacterium prausnitzii et de christensenella pour le traitement et la prevention d'une inflammation gastro-intestinale

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EP4003380A1 true EP4003380A1 (de) 2022-06-01

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US (1) US20220339207A1 (de)
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CA (1) CA3145274A1 (de)
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WO (1) WO2021013944A1 (de)

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