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• • 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
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  • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
  • C12N1/20—Bacteria; Culture media therefor
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
  • A23P10/00—Shaping or working of foodstuffs characterised by the products
  • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
• • 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
  • 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
  • A61K35/741—Probiotics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K39/02—Bacterial antigens
  • A61K39/0216—Bacteriodetes, e.g. Bacteroides, Ornithobacter, Porphyromonas
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/04—Anorexiants; Antiobesity agents
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
  • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
  • C12N1/20—Bacteria; Culture media therefor
  • C12N1/205—Bacterial isolates
• • 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
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K39/00—Medicinal preparations containing antigens or antibodies
  • A61K2039/70—Multivalent vaccine
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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  • C12R2001/00—Microorganisms ; Processes using microorganisms
  • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
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  • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
  • C12R2001/00—Microorganisms ; Processes using microorganisms
  • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
  • C12R2001/145—Clostridium

Definitions

• the present invention relates to particular bacteria for their use as a medicament, particularly for preventing or combating overweight, obesity, cardiometabolic diseases and inflammatory bowel diseases.
• the invention also provides compositions comprising such bacteria.
• Overweight and obesity are affecting all populations today in both developed and developing countries. They cause chronic diseases, such as cardiometabolic diseases, especially diabetes and cardiovascular diseases, but also certain cancers, neurodegenerative diseases and inflammatory bowel diseases, which affect a large portion of the world's population and become the first cause of death.
• a first objective of the invention is to propose a simple, effective and economical solution for dealing with this major health problem.
• pandemic of these chronic diseases seems to be linked to a combination of several factors: a bad diet like "western diet”, a sedentary lifestyle and factors affecting genetics and epigenetics.
• Another objective of the invention is therefore to propose a solution to fight in particular against overweight, obesity, cardiometabolic diseases and inflammatory bowel diseases by acting on the intestinal microbiome and in particular on bacteria. heritable.
• the microbiome is a set of microorganisms (bacteria, archaea, viruses and eukaryotes grouped into domains) that are specific to each individual. These microorganisms are found on the skin, in the mouth and the largest number in the digestive system which has about 3.3 million. This microbiome contains more than one hundred and fifty times more genes than the human genome.
• the different levels for classifying bacteria are: domain, phylum, class, order, family, genus, species and strain.
• the bacteria are also identifiable and characterizable by UTOs (Operational Taxonomic Units), a UTO corresponding to a grouping of strains of bacteria of the same species whose 16S rRNA sequences have a similarity of more than 97%.
• Meta-analysis with metagenomics composition and function of all genes
• metaproteomics protein analysis
• metabolomics metabolic profile
• RNA metatranscriptomics
• Each individual has his or her own microbiome that comes from its history and roots, but there are species common to many individuals. In particular, it is known that more than 85% of the species are common between Europe, the United States and Japan.
• the intestinal microbiome is not homogeneous. It varies in quantity and quality when it comes to the stomach, duodenum, jejunum, ileum and finally the colon where the more anaerobic bacteria. It is also known that some bacteria are found in the mucus lining the intestinal wall.
• the immune system the genetic system and the neurotransmitters (especially those linking the intestine and the brain) influence the microbiome, which makes its study even more complex.
• Cardiometabolic diseases such as diabetes have been shown to have a significant decrease in Clostridiales and an increase in Bacteriodetes in vitro or in animals, as well as a decrease in Roseburia intestinalis and Faecalibacterium pransnitzii, which would regulate glucose and glycemia through the permeability of the intestinal barrier, but again these findings do not allow to bring a satisfactory solution to fight against overweight, obesity and cardiometabolic diseases resulting therefrom because the number of different bacteria is too important.
• this solution is at best a decoy and at worst a danger by increasing the undesired bacteria which is the natural tendency of the microbiome in dysbiosis.
• Selective growth was also sought in vitro by crossing selected food on selected strain but it did not work in humans.
• probiotics as a "food" for developing selected bacteria.
• This solution is also not satisfactory because the developed probiotics have been limited to the food bacteria that are used in the first part of the intestine while the metabolically interesting bacteria are in the colon and nested in the mucus.
• it is difficult to demonstrate action on humans in the long run because the activity is highly random.
• the third solution proposed is the faecal implantation of normal or lean people bacteria to obese people according to a technique that works on mice. This technique has the disadvantage of trying to implant foreign strains that can be rejected and there is a possible transmission of carcinogenic signals according to the fears expressed by oncologists.
• the invention therefore aims to meet this need, proposing to use new specific bacteria acting particularly effectively to fight against overweight, obesity, cardiometabolic diseases and inflammatory bowel diseases.
• the invention relates to the use of particular bacteria selected and harvested from the microbiome of overweight or obese persons and having a metabolic syndrome.
• the invention relates to commensal, heritable, gram negative, strictly anaerobic and non-sporulated bacteria of the family of Christensenellaceae and belonging to a UTO characterized by a sequence of 16S rRNA SEQ ID No. 2.
• the bacteria according to the invention are remote (see phylogenetic tree Figure 1) from those already described for their use in the fight against overweight, obesity, cardiometabolic diseases and / or inflammatory bowel diseases.
• the bacteria according to the invention have a significantly demonstrated and very important efficacy against overweight, obesity, cardiometabolic diseases and inflammatory bowel diseases in humans, in particular by decreasing visceral fat. one part and intestinal permeability on the other hand. They have been specifically selected from a population of overweight or obese people with metabolic syndrome and are therefore ideally suited for use as an effective drug in humans with great adaptability for implantation in an inflammatory medium.
• the invention also relates to compositions comprising at least one of these bacteria.
• FIG. 1 represents the phylogenetic tree of the bacteria according to the invention.
• rRNA ribosomal ribonucleic acid
• 16S rRNA is meant the rRNA constituting the small subunit of ribosomes of prokaryotes. In bacteria, their sequence makes it possible to identify and characterize operational taxonomic units.
• obesity is meant a concentration of fat mass that is too high in the body with an increase in the volume of adipose tissue, the tissue containing these fats.
• Obese adult human beings have a BMI (Body Mass Index) greater than 30.
• cardiometabolic disease is meant a metabolic and / or cardiovascular disease. These cardiometabolic diseases can be induced by overweight and / or obesity. These may include pre-diabetes, diabetes, vascular and cardiac diseases, atherosclerosis, hyperlipidemia, hyperglycemia, NASH (non-alcoholic fatty liver disease), NAFLD non-alcoholic fatty liver), myocardial infarction, stroke, hypertension.
• “Use as medicine” means use for any curative or preventive effect with respect to human or animal diseases, as well as any use in humans, for the purpose of establishing a medical diagnosis or restoring, correcting or modifying their organic functions.
• the use as a medicament in the context of the present invention notably includes a use as a specific modulator of the microbiome to reconstitute an ecosystem beneficial to the health of the host.
• cardiometabolic risk or “metabolic syndrome” is meant a syndrome that includes at least three risk factors selected from: waist circumference, blood glucose, HDL cholesterol, triglycerides and blood pressure, which leads to cardiometabolic diseases.
• overweight is meant a concentration of fat mass too high in the body with an increase in the volume of adipose tissue, tissue containing these fats. Overweight adult humans have a BMI (body mass index) greater than 25.
• infant transplant is meant stool intended to be transplanted into an individual and coming either from the individual himself taken before treatment and implanted after treatment, or from another individual deemed healthy.
• OTU or “Operational Taxonomic Unit” is meant a grouping of bacteria of the same species whose 16S rRNA sequences have a similarity of more than 97%.
• a UTO characterized by a 16S "X” rRNA sequence includes bacteria with a 16S rRNA sequence having a greater than 97.5% similarity to the "X" sequence.
• the subject of the invention is a commensal, inherently gram negative, strictly anaerobic and non-sporulated bacterium of the family Christensenellaceae and belonging to a UTO characterized by a sequence of 16S rRNA ID No. 2 (referred to as UTO 2 for the present description. ), for use as a medicine.
• UTO 2 bacteria are commensal and heritable bacteria present in the human intestinal mucus.
• They preferably have a diameter of 0.5 ⁇ .
• They can be especially cultured in a pH between 7 and 8 under strict anaerobic conditions, at a temperature of 37 ° C for 4 days on yeast with supplementation of feeder glucose.
• the 16S rRNA sequences that specifically and uniquely identify these bacteria are far removed from the 16S rRNA sequences of known bacteria of the same family and genus such as Christensenella minuta, Christensenella massiliensis, Christensenella timonensis. They are below 90% Christensenella minuta in the phylogenetic tree (see Figure 1) and are well individualized.
• the bacteria according to the invention can be harvested and selected from the intestinal microbiome of a population of overweight or obese people with metabolic syndrome. They are correlated with the improvement of many factors that are characteristic of overweight, obesity, cardiometabolic diseases or inflammatory bowel disease, and in particular a decrease in visceral fat.
• the bacteria according to the invention can be harvested in particular by sampling fecal matter, in particular fecal material from an overweight or obese person and metabolic syndrome whose FIHT and TDRG1 genes have not undergone genetic variation, and more precisely whose FIHT gene has not undergone a rs74331972 variation and whose TDRG1 gene has not undergone a rs 1433723 variation.
• the bacteria that are useful according to the invention can be administered to humans by any suitable mode of administration, in particular orally or rectally.
• the bacteria according to the invention are especially capable of:
• the bacteria according to the invention are therefore particularly useful in the treatment of overweight, obesity, metabolic syndrome, pre-diabetes, diabetes, vascular and cardiac diseases, atherosclerosis, hyperlipidemia, hyperglycemia, NASH (non-alcoholic fatty liver disease) and / or NAFLD (non-alcoholic fatty liver disease) and / or IBD (Inflammatory Bowel Disease), in particular the disease of Crohn.
• the invention makes it possible to act on the reconstitution of mucus, of the epithelium and the increase of the impermeability of the intestinal barrier for the modulation of tight junctions in order to reduce the endotoxemia and the blood translocation of bacteria and parasites.
• endotoxin lipopolysaccharide LPS
• the inflamed epithelium is deficient with very open tight junctions that allow bacteria and LPS to pass. This phenomenon is due to inflammation of the intestine and causes low grade chronic inflammation in the body.
• the bacteria useful according to the invention are particularly suitable for persons with a BMI greater than 25 and in particular greater than 30 and / or persons with hypertriglycaemia.
• UTO 2 bacteria makes it possible to increase the efficient bacterial population of the Christensenellaceae family without increasing the potentially dangerous bacteria such as Catabacter hongkongensis from the same family and close to Christensenella minuta.
• the bacteria according to the invention can be used at the same time as a food rebalancing and / or caloric restriction.
• Food rebalancing can consist of especially to eliminate from the diet deleterious nutrients for the microbiome: fructose and trans fatty acids.
• the caloric restriction is preferably slight, about 600 kcal / day. In particular, it makes it possible to modulate glucose homeostasis, protein turnover and lipogenesis.
• the bacteria according to the invention can be used at a daily unit dose of 10 4 to 10 12 (in number of bacteria), preferably between 10 4 to 10 12 .
• the bacteria according to the invention are administered at a daily to weekly frequency.
• a frequency makes it possible to keep a colony of bacteria according to the invention sufficient in the microbiome and to prevent the mortality of the bacteria being greater than the growing bacteria.
• the frequency is determined according to several criteria, in particular the importance of the symptom to be treated, the importance of visceral fat to be lost, the importance of hyperglycemia or hypertriglyceremia or the frequency of diarrhea.
• the cure will last until the desired result is obtained; maintenance treatment may be recommended for cases where the implantation of bacteria has been long.
• a stool test or mucus sample to test for UTO 2 is not mandatory for all patients at the beginning of treatment because it is a heritable bacterium directly related to visceral fat. However, it may be necessary for patients with very high BMI or high inflammation (CRP us). Similarly, if after several months of treatment the result depending on the desired effects (decrease in waist circumference, weight loss, decrease in hyperglycemia, etc.) is not achieved, it is preferable to perform a stool analysis. to verify that the bacteria have nested well or if highly disturbed genetic or epigenetic factors require the use of a higher administration frequency than originally planned.
• the advantage of bacteria of the Christensenellaceae family is to have a good correlation between the presence of these bacteria in the stool and in the mucus which does not oblige to take samples by endoscopy in the colon.
• the bacteria according to the invention can be used as part of a personalized medicine. Indeed, it is possible to adapt the treatment to the patient's genetics to know to what extent he will respond to the treatment and what is the dose to use.
• the genes which are known to vary are FHIT with the variation rs 74331972 and TDRGl variant rs 1433723. It is thus possible to use a genetic analysis of the host. in parallel with the genetic analysis of the microbiome to fully personalize the treatment of the patient in severe cases with possible resistance to treatment in order to adjust the dose to be administered.
• the bacteria according to the invention can be used alone directly, but preferentially they are used within a composition.
• the subject of the invention is therefore also a composition
• a composition comprising at least one OTU 1, that is to say at least one heritable, gram negative, strictly anaerobic and non-sporulated commensal bacterium of the family of Christensenellaceae, and belonging to a UTO characterized by a 16S rRNA sequence SE ID NO: 1.
• composition also comprises excipients, known to those skilled in the art and conventionally used in the pharmaceutical industry, to be adapted according to the galenic form of the composition.
• composition according to the invention comprises the combination:
• the combination of the bacteria according to the invention belonging to UTO 2 and bacteria according to the invention belonging to UTO 1 makes it possible to obtain a greater effect on the desired therapeutic applications.
• the UTO 2 and / or UTO 1 bacteria may also be associated with other bacteria in the composition.
• the composition may also include at least one commensal, inheritable bacterium of the family Christensenellaceae and belonging to a UTO (referred to as UTO 3 for the present description) characterized by a 16S SEO ID No. 3 rRNA sequence and / or less a bacterium belonging to a UTO (called UTO 4 for the present description) characterized by a 16S SEO ID No. 4 rRNA sequence and / or at least one bacterium belonging to a UTO (referred to as UTO for the present description) characterized by a 16S SEO ID No. 5 rRNA sequence and / or at least one bacterium belonging to a UTO (called UTO 6 for the present description) characterized by a sequence of 16S SEO ID RNA No.
• UTO 7 for the present description
• UTO 8 for the present description
• UTO 9 for the present description
• UTO 10 for the present invention
• UTO deoxyribonucleic acid
• UTO 12 deoxyribonucleic acid
• UTO 13 a sequence of 16S SEO ID No. 13 rRNA
• UTO 14 a 16S SEO ID No. 14 rRNA sequence
• bacteria are capable of acting on the same factors as the bacteria that are useful according to the invention, but can hardly be used alone because they are less frequent in the microbiome and thus their implantation is more random. However, their use in combination with the bacteria according to the invention improves the effectiveness of the latter and strengthens the ecosystem of Christensenellaceae.
• composition according to the invention may also comprise one or more methanogenic bacteria of the family Methanobacteriaceae, of the genus Methanobacterium and / or Methanobrevibacter and / or Methanosphaera and / or Methanothermobacter, in particular Methanothermobacter smithii, Methanogens facilitate the implantation of Christensenellaceae in especially in obese people or people with diabetes but should be used with caution in inflammatory bowel disease.
• Methanogens facilitate the implantation of Christensenellaceae in especially in obese people or people with diabetes but should be used with caution in inflammatory bowel disease.
• It may also comprise one or more bacteria of the following species, genus or order: Marvinbryantia formatexigens and / or Bacteroides thetaiotaomicron and / or Akkermansia muciniphila and / or Faecalibacterium prausnitzii and / or Clostridium thermocellum and / or Dehalobacteriaceae and / or Oscillospira and / or Mogibacteriaceae and / or Ruminococcaceae and / or Ruminococcus and / or Lachinospiraceae and / or Lachinospira and / or Bacteroidaceae and / or Rikenellaceae and / or Clostridium and / or Clostridiales.
• All of these bacteria may be bacteria of known strains currently cultivated or may be new strains, particularly strains harvested from the feces of an overweight or obese person and metabolic syndrome to obtain strains resistant to inflammation characteristic of overweight or obese people. These bacteria are known to have an influence on the regulation of the weight in the mouse even if most are not heritable thus with an unknown mode of action. The most likely scientific hypothesis is that they strengthen the ecosystem of the Christensenellaceae family.
• the bacteria that are useful according to the invention can also be used in combination with at least one other bacterium chosen from Christensenella massiliensis, Christensenella timonensis and Christensenella minuta. Again, these bacteria can be harvested from the feces of an overweight or obese person and metabolic syndrome to obtain inflammation-resistant strains characteristic of overweight or obese individuals. These bacteria are of the Christensenellaceae family with a less convincing action in the clinical experience on obese patients with a cardiometabolic risk but they allow to create both a synergy but especially a strengthening of the ecosystem of the bacteria of the invention.
• compositions according to the invention may also comprise other constituents, in particular at least one amino acid and / or at least one peptide. It may be in particular threonine, leucine, serine, proline, alanine, glycine, glutamine, glutamic acid, tryptophan and / or at least one peptide containing at least one of these amino acids. According to one variant, these amino acids can be administered in parallel with the bacteria according to the invention, but in an independent composition.
• the quantity of each of the amino acids or biopeptides is preferably between 500 mg and 1 g per day.
• compositions according to the invention may also comprise at least one probiotic and / or at least one prebiotic. It may be for example oligosaccharides, in particular RS4 for prebiotics or lactic ferments for probiotics. Probiotics can improve the quantitative dysbiosis and general health of the microbiota. Prebiotics make it possible to increase the food of the bacteria according to the invention which have been implanted. Preferably prebiotics and / or probiotics are administered at the beginning of the treatment with the bacteria according to the invention.
• the bacteria according to the invention are preferably used live.
• the bacteria present are preferably for at least 50% of living bacteria (percentage by number), more preferably at least 90%.
• the bacteria that are useful according to the invention and the compositions that include them can be in any form.
• the bacteria and / or the composition are in freeze-dried form.
• the compositions according to the invention are in the form of powder, microencapsulated powder, capsule, capsugel, tablet, or fecal transplant.
• the compositions according to the invention are in a gastro-resistant form, in particular in a gastro-resistant form intended to be absorbed at the intestinal level, preferably at the level of the colon, in particular at the level of the terminal ileum or colon entry.
• compositions according to the invention are manufactured by simple mixing of the constituents and / or by conventional methods known to those skilled in the art adapted to the desired dosage forms.
• the compositions according to the invention can be used for all the therapeutic applications, in particular all the therapeutic applications of the bacteria useful according to the invention as described in the present application.
• the compositions according to the invention are used at a daily unit dose for each bacterium present in the composition (UT02 and other bacteria possibly present) of 10 4 to 10 12 . It is possible to adapt the dosage of the bacteria present in the composition according to several criteria, in particular according to the amount of said bacteria found in the stool taken from the persons to be treated.
• the bacteria and compositions according to the invention can be given to adults, the elderly, children and adolescents.
• the dosage can be the same for all patients regardless of age.
• the invention makes it possible to reduce the therapeutic failures which are numerous either by the abandonment of the treatment in progress and most often at the beginning, or by the recovery of weight after a few months and with a larger recovery than before.
• visceral fat either through the continuation of chronic cardiometabolic and / or inflammatory diseases and their acute manifestations.
• composition example according to the invention is a composition in freeze-dried form comprising UTO 2 and at least one suitable excipient.
• This exemplary composition according to the invention is a composition in freeze-dried form comprising UTO 2 and UTO 1 and at least one suitable excipient.
• Example 3 is a composition in freeze-dried form comprising UTO 2 and UTO 1 and at least one suitable excipient.
• composition example according to the invention is a composition in freeze-dried form comprising UTO 1, UTO 2, UT03, UTO 4, UTO 5, UTO 6, UTO 7, UTO 8, UTO 9, UTO 10, UTO 11, UTO 12, UTO 13, IOTU14 and IOTU15 and at least one suitable excipient.
• Example 4
• composition according to the invention is a composition in freeze-dried form comprising UTO 1, UTO 2 and Akkermansia muciniphali and at least one suitable excipient.
• composition according to the invention is a composition in freeze-dried form comprising UTO 1, UTO 2 and Methanobrevibacter smithii and at least one suitable excipient.
• composition according to the invention is a composition in freeze-dried form comprising UTO 1, UTO 2, Christensenella massiliensis, Christensenella timonensis, and Christensenella minuta and at least one suitable excipient.
• UTO 1 UTO 2
• UTO 2 Christensenella massiliensis
• Christensenella timonensis Christensenella minuta
• at least one suitable excipient is a composition in freeze-dried form comprising UTO 1, UTO 2, Christensenella massiliensis, Christensenella timonensis, and Christensenella minuta and at least one suitable excipient.
• composition according to the invention is a composition in lyophilized form comprising UTO 1, UTO 2, Faecalibacterium prausnitzii, Oscillospira and Lachinospira and at least one suitable excipient.
• a product known to combat overweight, obesity and metabolic syndrome was administered with a caloric restriction of 600 kcal for a period of 12 weeks.
• Patients' stool was collected at the beginning and end of the study after 12 weeks, to detect impacts on the correlations between the bacteria present in the stool and the evolution of clinical signs.
• the main criterion retained for the evolution of the metabolic syndrome was the visceral fat mass measured by CTScan and the secondary criterion weight.
• the determination and characterization of the bacteria was performed by 16S rRNA analysis, confirmed by qPCR and a shotgun metagenomic.
• the increase of bacteria according to the invention in the microbiome is directly related to a decrease in weight and body fat in humans.
• the bacteria according to the invention therefore play a key role in the fight against overweight, obesity, cardiometabolic diseases and inflammatory diseases, in particular related to visceral fat, and can be used for this purpose.
• the UTOs 1 and 2 according to the invention were already present in an amount sufficient to be detected and individualized in the patients of the study despite their overweight or obesity and the metabolic syndrome.
• the presence of these bacteria in a highly inflammatory environment means that they have become resistant to inflammation and that both FHIT and TDRG1 genes have partially resisted the epigenetics of parent feeding or epigenetic transmission.

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• 2017
  • 2017-03-10 FR FR1770237A patent/FR3063646B1/fr active Active
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• 2018
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• 2021
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