EP-4739145-A1 - METHOD FOR ESTABLISHING A COMBINATION THERAPY AND CORRESPONDING PHARMACEUTICAL AND NUTRITIONAL COMBINATIONS

Abstract

The present invention provides a method for establishing a combination therapy for modulating an intestinal microbiome and a pharmaceutical or nutritional combination for modulating an intestinal microbiome, in particular for use in the treatment of intestinal dysbiosis, said combination comprising (i) a dietary fiber and/or a carbohydrate source and (ii) at least one bacterial strain identified in a method according to the invention.

Inventors

• LEVENTHAL, Gabriel
• de Wouters, Tomas
• THABUIS, Clémentine

Assignees

• PharmaBiome AG

Dates

Publication Date

20260513

Application Date

20240703

Claims (1)

1. CLAIMS 1- A combination therapy comprising (i) at least one bacterial strain and (ii) at least one dietary fibre or carbohydrate source, wherein said combination therapy comprises: (a) at least one bacterial strain selected from the genera Lachnospira, UMGS1375, CAG-41, CAG-274 and UMGS1441, and (b) pectin (PE); (a) at least one bacterial strain selected from the genera Ruminococcus_D, Lachnospira, CAG-41, TF01-11, UMGS1441, Ruminiclostridium_E, Agathobacter, Acetatifactor and Kineothrix; and (b) pea fibre (PF); (a) at least one bacterial strain selected from the genera UMGS1375, Lachnospira, Olsenella_E, Murimonas, and Acetatifactor and (b) arabinogalactan (AG); (a) at least one bacterial strain selected from the genera UMGS1375, Acutalibacter, Parabacteroides, Fusicatenibacter, Clostridium_A, Eisenbergiella, Agathobacter, Murimonas and Ruminococcus_A; and (b) resistant dextrin (RD); (a) at least one bacterial strain selected from the genera Blautia_A, Agathobacter, Bifidobacterium, Fusicatenibacter, Acetatifactor, Murimonas; and (b) xylan (XY); (a) at least one bacterial strain selected from the genera UMGS1375, Akkermansia, Ruminococcus_E, GCA- 900066135, Eubacterium_G, Agathobacter, Barnesiella, Mediterraneibacter and CAG-45; and (b) mucin (MU); (a) at least one bacterial strain selected from the genera Anaerostipes, Parabacteroides, Phascolarctobacterium_A, Bacteroides and Phascolarctobacterium; and (b) yeast extract (YE); and/or (a) at least one bacterial strain selected from the genera Agathobacter, Roseburia, Coprococcus, CAG-45, Acetatifactor and Ruminococcus_E; and (b) soluble starch (SS). 2- The combination therapy of claim 1, said combination therapy comprising: (a) at least one bacterial strain selected from the group consisting of Acutalibacter timonensis, Acutalibacter sp003612555, Parabacteroides distasonis, Parabacteroides merdae, Fusicatenibacter saccharivorans, Clostridium_A leptum, Eisenbergiella sp900066775, Eisenbergiella massiliensis, Eisenbergiella tayi, UMGS1375 sp900066615, Agathobacter rectalis, Agathobacter faecis, Murimonas intestini, Ruminococcus_A sp000437095, Ruminococcus_A sp003011855; and (b) resistant dextrin (RD); (a) at least one bacterial strain selected from the group consisting of CAG-41 sp900066215, UMGS1441 sp900551755, Lachnospira eligens, Lachnospira rogosae, Lachnospira sp003451515, Lachnospira sp003537285, CAG-274 sp900545305 and UMGS1375 sp900066615 ; and (b) pectin (PE); (a) at least one bacterial strain selected from the group consisting of CAG-41 sp900066215, TF01-11 sp001414325, UMGS1441 sp900551755, Lachnospira rogosae, Lachnospira sp003537285, Ruminiclostridium_E siraeum, Agathobacter faecis, Agathobacter rectalis, Acetatifactor sp900066365, Ruminococcus_D bicirculans, Ruminococcus_D sp900604945, Kineothrix alysoides and (b) pea fibre (PF); (a) at least one bacterial strain selected from the group consisting of UMGS1375 sp900066615, Olsenella_E sp003609875, Murimonas intestini, Acetatifactor sp900066565, Lachnospira eligens and (b) (b) arabinogalactan (AG); (a) at least one bacterial strain selected from the group consisting of UMGS1375 sp900066615, Akkermansia muciniphila, Ruminococcus_E bromii, GCA-900066135 sp900066135, Eubacterium_G ventriosum, Eubacterium_G sp000434315, Agathobacter faecis, Agathobacter rectalis, Barnesiella intestinihominis, Mediterraneibacter faecis, Mediterraneibacter torques, CAG-45 sp900066395 and (b) mucin (MU); (a) at least one bacterial strain selected from the group consisting of Anaerostipes sp90006670, Parabacteroides merdae, Phascolarctobacterium_A succinatutens, Bacteroides faecichinchillae, Bacteroides ovatus, Phascolarctobacterium faecium and (b) yeast extract (YE); (a) at least one bacterial strain selected from the group consisting of Agathobacter rectalis, Agathobacter faecis, Roseburia intestinalis, Roseburia sp001940165, Coprococcus eutactus, CAG-45 sp900066395, Acetatifactor sp900066365, Ruminococcus_E sp003438075 and (b) soluble starch (SS); and/or (a) at least one bacterial strain is selected from the group consisting of Agathobacter rectalis, Blautia_A sp003471165, Blautia_A sp003471165, Bifidobacterium adolescentis, Fusicatenibacter saccharivorans, Acetatifactor sp900066565, Murimonas intestini and (b) xylan (XY). 3- The combination therapy according claim 1 or 2, wherein the at least one bacterial strain is comprised in a bacterial consortium comprising no more than 15 different bacterial strains, preferably between 5 to 15 different bacterial strains, more preferably between 6 and 10 different bacterial strains. 4- The combination therapy according to claim 3, wherein the bacterial consortium comprises: - one or several bacterial strain(s) able to convert primary substrates into lactate (A4); - one or several bacterial strain(s) able to convert lactate into butyrate (B3); and/or - one or several bacterial strain(s) able to convert lactate into propionate (B4). 5- The combination therapy according claim 4, wherein: - the one or several bacterial strain(s) able to convert primary substrates into lactate (A4) transform at least 30%, at least 50%, more preferably at least 60% of the total carbon transformed into the combined metabolites formate (FO), lactate (LT), succinate (SU), acetate (AA), butyrate (BA), propionate (PA) and Ethanol (Et) into lactate when grown for 48 hours in single culture on standard medium; - the one or several bacterial strain(s) able to convert lactate into butyrate (B3) degrade at least 20% of lactate in medium and transform at least 20%, preferably at least 50%, more preferably at least 65% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into butyrate when grown for 48 hours in single culture on standard medium supplemented with lactate; and/or - the one or several bacterial strain(s) able to convert lactate into propionate (B4) degrade at least 20% of lactate in medium and transform at least 20%, preferably at least 50%, more preferably at least 65% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into propionate when grown for 48 hours in single culture on standard medium supplemented with lactate. 6- The combination therapy according to claim 4 or 5, wherein - the one or several bacterial strain(s) able to convert primary substrates into lactate (A4) are selected from the genera Agathobacter, Bacteroides, Bariatricus, Bifidobacterium, Collinsella, Enterococcus, Lacticaseibacillus/Lactobacillus, Longicatena, Merdisoma, Peptostreptococcus, Roseburia, Streptococcus and Sutterella; preferably from the genera Agathobacter, Bacteroides, Bariatricus, Collinsella, Enterococcus, Lacticaseibacillus/Lactobacillus, Peptostreptococcus, Streptococcus, and Sutterella; more preferably from the genera Agathobacter, Bacteroides, Bariatricus, Collinsella, Enterococcus, Lacticaseibacillus/Lactobacillus, Streptococcus, and Sutterella; - the one or several bacterial strain(s) able to convert lactate into butyrate (B3) are selected from the genera Anaerobutyricum, Anaerostipes and Eubacterium; preferably from the genera Anaerobutyricum and Anaerostipes; and/or - the one or several bacterial strain(s) able to convert lactate into propionate (B4) are selected from the genera Anaerotignum, Clostridium, Coprococcus_A, Frisingococcus and Veillonella; preferably from the genera Anaerotignum genus, Coprococcus_A, Frisingococcus and Veillonella. 7- The combination therapy according to any one of claims 3-6, wherein the bacterial consortium comprises: - one or several bacterial strain(s) able to convert primary substrates into formate (A1); - one or several bacterial strain(s) able to convert primary substrates into acetate (A2); - one or several bacterial strain(s) able to convert formate into acetate (B1); and/or - one or several bacterial strain(s) able to convert acetate into butyrate (B2). 8- The combination therapy according to claim 7, wherein: - the one or several bacterial strain(s) able to convert primary substrates into formate (A1) transform at least 20%, at least 25%, more preferably at least 30% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into formate when grown for 48 hours in single culture on standard medium; - the one or several bacterial strain(s) able to convert primary substrates into acetate (A2) transform at least 30%, at least 50%, more preferably at least 60% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into acetate when grown for 48 hours in single culture on standard medium; - the one or several bacterial strain(s) able to convert formate into acetate (B1) degrade at least 20% of formate in medium and transform at least 20%, preferably at least 50%, more preferably at least 65% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into acetate when grown for 48 hours in single culture on standard medium supplemented with formate; and/or - the one or several bacterial strain(s) able to convert acetate into butyrate (B2) degrade at least 20% of acetate in medium and transform at least 20%, preferably at least 50%, more preferably at least 65% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Ethanol into butyrate when grown for 48 hours in single culture on standard medium or standard medium supplemented with FO, LT and/or SU. 9- The combination therapy according to claim 7 or 8, wherein: - the one or several bacterial strain(s) able to convert primary substrates into formate (A1) are selected from the genera Anaerobutyricum, Bacteroides, Blautia, Collinsella, Coprococcus, Dorea, Erysipelatoclostridium, Escherichia, Eubacterium, Faecalibacterium, Lachnospira, Longicatena, Ruminococcus, and Sellimonas; preferably from the genera Blautia, Coprococcus, Dorea, Erysipelatoclostridium, Faecalibacterium, Lachnospira and Ruminococcus; more preferably from the genera Coprococcus, Dorea, Faecalibacterium and Ruminococcus; - the one or several bacterial strain(s) able to convert primary substrates into acetate (A2) are selected from the genera Acidaminococcus, Acutalibacter, Bifidobacterium, Blautia, Clostridium, Clostridium_E, Clostridium_Q, Collinsella, Copromonas, Desulfovibrio, Dorea, Enterocloster, Escherichia, Eubacterium, Hungatella, Hungatella_A, Oliverbapstia, Peptoniphilus, Peptostreptococcus, Phocaeicola, Rhiziobiaceae genus, Ruminococcus, Sellimonas and Veillonella; preferably from the genera Bifidobacterium, Blautia, Clostridium_Q, Clostridium_E, Desulfovibrio, Dorea, Eubacterium, Oliverpabstia, and Rhiziobiaceae genus; more preferably from the genera Bifidobacterium, Blautia, Clostridium_E, Desulfovibrio, Dorea, Eubacterium, and Rhiziobiaceae genus; - the one or several bacterial strain(s) able to convert formate into acetate (B1) are selected from the genera Blautia and Eubacterium; and/or - the one or several bacterial strain(s) able to convert acetate into butyrate (B2) are selected from the genera Agathobacter, Anaerobutyricum, Anaerostipes, Anaerotignum, Desulfovibrio, Dysosmobacter, Faecalibacterium, Longicatena and Roseburia; preferably from the genera Agathobacter, Anaerobutyricum, Anaerostipes, Desulfovibrio, Faecalibacterium and Roseburia. 10- The combination therapy according to any one of claims 3-9, wherein the bacterial consortium comprises: - one or several bacterial strain(s) able to convert primary substrates into succinate (A6); and/or - one or several bacterial strain(s) able to convert succinate into propionate (B5). 11- The combination therapy according to claim 10, wherein: - The one or several bacterial strain(s) able to convert primary substrates into succinate (A6) transform at least 30%, at least 50%, more preferably at least 60% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into succinate when grown for 48 hours in single culture on standard medium; and/or - The one or several bacterial strain(s) able to convert succinate into propionate (B5) degrade at least 20% of succinate in medium and transform at least 20%, preferably at least 50%, more preferably at least 65% of the total carbon transformed into the combined metabolites FO, LT, SU, AA, PA, BA and Et into propionate when grown for 48 hours in single culture on standard medium supplemented with succinate. 12- The combination therapy according to claim 10 or 11, wherein: - The one or several bacterial strain(s) able to convert primary substrates into succinate (A6) are selected from the genera Acutalibacter, Bacteroides, Oliverbapstia, Parabacteroides, Phocaeicola and Prevotella; preferably from the genera Acutalibacter nov genus, Bacteroides, Parabacteroides, Phocaeicola and Prevotella; more preferably from the genera Acutalibacter nov genus, Bacteroides, Phocaeicola and Prevotella; and/or - The one or several bacterial strain(s) able to convert succinate into propionate (B5) are selected from the genera Dialister, Flavonifractor, Phascolarctobacterium and Veillonella; preferably from the genera Dialister, Flavonifractor, Phascolarctobacterium and Phascolarctobacterium_A. 13- The combination therapy according to any one of claims to 3-12, wherein the at least one bacterial strain is comprised in a bacteria consortium, said bacteria consortium comprising or consisting essentially of Agathobacter rectalis; Anaerostipes caccae or Anaerobutyricum hallii; Ruminococcus bromii; Bifidobacterium adolescentis; Lactobacillus rhamnosus; Blautia hydrogenotrophica; Phascolarctobacterium faecium and a bacterium selected from the group consisting of Bacteroides xylanisolvens, Prevotella copri and Acutalibacter species having at least 95% identity with SEQ ID NO: 6. 14- The combination therapy according to any one of claims 3-13, wherein the at least one bacterial strain is comprised in a bacteria consortium, said bacteria consortium comprising or consisting essentially of Agathobacter rectalis; Anaerostipes caccae; Ruminococcus bromii; Bifidobacterium adolescentis; Lactobacillus rhamnosus; Blautia hydrogenotrophica; Phascolarctobacterium faecium and a bacterium selected from the group consisting of Bacteroides xylanisolvens, Prevotella copri and Acutalibacter nov. specie. 15- The combination therapy according to any one of claims 3-14, wherein the at least one bacterial strain is comprised in a bacteria consortium, said bacteria consortium comprising or consisting essentially of: - Agathobacter rectalis; Anaerostipes caccae; Ruminococcus bromii; Bifidobacterium adolescentis; Lactobacillus rhamnosus; Blautia hydrogenotrophica; Phascolarctobacterium faecium and Bacteroides xylanisolvens; - Agathobacter rectalis; Anaerostipes Caccae; Ruminococcus bromii; Bifidobacterium adolescentis; Lactobacillus rhamnosus; Blautia hydrogenotrophica; Phascolarctobacterium faecium and Prevotella copri; or - Agathobacter rectalis; Anaerostipes Caccae; Ruminococcus bromii; Bifidobacterium adolescentis; Lactobacillus rhamnosus; Blautia hydrogenotrophica; Phascolarctobacterium faecium and Acutalibacter nov. specie having at least 95% identity with SEQ ID NO 6. 16- The combination therapy according to any one of claims 1 to 15, wherein the combination therapy comprises or consists of: a) a first pharmaceutical or nutraceutical composition comprising the at least one bacterial strain, optionally comprised in a bacteria consortium, and a second pharmaceutical or nutraceutical composition comprising the at least one dietary fibre and/or carbohydrate source; c) a pharmaceutical or nutraceutical composition comprising (I) the at least one bacterial strain, optionally comprised in a bacteria consortium, and (II) the dietary fibre and/or carbohydrate source. 17- A pharmaceutical or nutraceutical composition comprising a combination therapy according to any one of claims 1-15. 18- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Lachnospira and (II) pea fiber, pectin and/or arabinogalactan, preferably pectin. 19- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Ruminococcus_D and (II) pea fiber. 20- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus UMGS1375 (Hominsplanchenecus) and (II) arabinogalactan, resistant dextrin and/or pectin, preferably arabinogalactan and/or pectin. 21- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Blautia_A and (II) xylan. 22- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Parabacteroides and (II) resistant dextrin and optionally yeast extract. 23- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Acutalibacter and (II) resistant dextrin. 24- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Akkermansia and (II) mucin. 25- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Agathobacter and (II) pea fiber, resistant dextrin, mucin and/or xylan, preferably pea fiber. 26- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus CAG-41 and (II) pea fiber and/or pectin, resistant dextrin, mucin and/or xylan, preferably pea fiber 27- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus TF01-11 and (II) pea fiber. 28- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Acetatifactor and (II) arabinogalactan, pea fiber, soluble starch and/or xylan, preferably pea fiber. 29- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Fusicatenibacter and (II) xylan. 30- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Anaerostipes and (II) yeast extract. 31- The pharmaceutical or nutraceutical composition of claim 17, wherein the composition comprises (I) a bacterial strain of the genus Eisenbergiella and (II) resistant dextrin. 32- The pharmaceutical or nutraceutical composition of any one of claims 17-31, wherein the composition further comprises: - propionate, acetate and/or butyrate; and/or - a pharmaceutical excipient or carrier. 33- The combination therapy according to any one of claims 1 to 16 or the pharmaceutical or nutraceutical composition according to any one of claims 17 to 32, for use as a medicament. 34- The combination therapy according to any one of claims 1 to 16 or the pharmaceutical or nutraceutical composition according to any one of claims 17 to 32, for use in the treatment of intestinal dysbiosis or of a disease or disorder caused by an intestinal dysbiosis. 35- A method for treating a patient suffering from an intestinal dysbiosis or from a disease or disorder caused by an intestinal dysbiosis, comprising administering a therapeutic amount of the combined therapy according to any one of claims 1 to 16 or the pharmaceutical or nutraceutical composition according to any one of claims 17 to 32 to said patient. 36- The method of claim 35, wherein the method further comprises a step of selecting a patient as suitable for treatment with the combined therapy or the pharmaceutical or nutraceutical composition, wherein the patient is selected as suitable if the at least one bacterial strain of the combined therapy is under- represented in the intestinal microbiome of said patient. 37- Use of the combination therapy according to any one of claims 1 to 16 or the pharmaceutical or nutraceutical composition according to any one of claims 17 to 32, for the manufacture of a medicament for treating an intestinal dysbiosis or a disease or disorder caused by or related to an intestinal dysbiosis. 38- The combination therapy for use according to claim 34, the method of claim 35 or 36 or the use of claim 37, wherein the intestinal dysbiosis is caused by an antibiotic treatment. 39- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is selected from the group consisting of an inflammatory disease, an auto-immune disease, a cancer, a bacterial infection and a brain disorder, preferably in from the group consisting of infection by vancomycin resistant enterococci (VRE), infection by carbapenem resistant enterococci (CRE), post-infectious diarrhea; Parkinson’s disease (PD), herosclerotic cardiovascular disease (ACVD), coronary artery disease (CAD), hypertension inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohns’s disease (CD); impaired glucose tolerance (IGT), type 1 diabetes (T1D), type 2 diabetes (T2D), rheumatoid arthritis (RA); multiple sclerosis (MS); graft versus host disease (GvHD); gastrointestinal cancer, adenoma, colorectal cancer (CRC), acute myeloid leukemia (AML); gastritis, colitis, gastroenteritis, gingivitis, nosocomial infection and Clostridium difficile infection (CDI). 40- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is acute myeloid leukemia (AML). 41- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is inflammatory bowel disease (IBD). 42- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is a complication following post-hematopoietic stem cell transplantation (HSCT), in particular graft versus host disease (GvHD). 43- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is impaired glucose tolerance (IGT) and/or type 1 diabetes (T1D). 44- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is type 2 diabetes (T2D). 45- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is cancer, in particular adenoma or colorectal cancer (CRC). 46- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is Parkinson’s disease (PD). 47- The combination therapy for use according to claim 34 or 38, the method of claim 35, 36 and 36 or the use of claim 37 or 38, wherein the disease or disorder is herosclerotic cardiovascular disease (ACVD), coronary artery disease (CAD) and/or hypertension. 48- A method for establishing a combination therapy for modulating an intestinal microbiome, comprising the steps of: a) Providing a microbiome sample distributed into at least two microbiome test samples, b) Growing a first microbiome test sample of step (a) on a reference substrate; c) Determining an absolute or relative abundance of individual microbe population in the first microbiome test sample at the end of step (b); d) Growing a second microbiome test sample of step (a) on a substrate comprising a nutritionally or therapeutically effective amount of - dietary fibers selected from the group of resistant dextrin RD, pectin PE, pea fiber PF, and arabinogalactan AG; or - a carbohydrate source selected from the group of soluble starch SS, xylan XY, yeast extract YE, mucin MU; e) Determining an absolute or relative abundance of individual microbe population in the second microbiome test sample at the end of step (d); f) Determining microbe population differentially enriched between the first and the second test sample by subtracting the absolute or relative abundance of an individual microbe population of step c) from the absolute or relative abundance of the same individual microbe population of step e); g) Attributing the enriched microbe population of step (f) to the specific substrate comprising resistant dextrin RD, pectin PE, pea fiber PF, arabinogalactan AG; soluble starch SS, xylan XY, yeast extract YE or mucin MU; h) Developing a pharmaceutical or nutritional combination for modulating an intestinal microbiome, said combination comprising (I) at least the enriched microbe population of step f); and (II) the substrate to which the enriched microbe population was attributed to in step f). 49- A combination therapy comprising or consisting of (i) at least one substrate, said substrate being at least one dietary fibre selected from the group of resistant dextrin (RD), pectin (PE), pea fibre (PF), and arabinogalactan (AG) and/or at least one carbohydrate source selected from the group of soluble starch (SS), xylan (XY), yeast extract (YE) and mucin (MU); and (ii) at least one bacterial strain, wherein the combination therapy has been developed by the method of claim 48.

Description

METHOD FOR ESTABLISHING A COMBINATION THERAPY AND CORRESPONDING PHARMACEUTICAL AND NUTRITIONAL COMBINATIONS FIELD OF THE INVENTION The present invention relates to the field of microbiology. It provides methods for establishing a combination therapy, pharmaceutical and nutritional combinations established by means of such method, compositions comprising probiotics forming part of such combinations, and uses thereof. BACKGROUND OF THE INVENTION Microbiomes are an essential contributor to the metabolic activity in the human gastrointestinal tract. The fermentation of otherwise indigestible nutritional components like dietary fibers relies on a complex interplay between the distributed metabolic activities across the individual bacterial members. Microbiome composition is diverse across individuals, and it has been suggested that this complexity might be reduced by describing microbiome composition not in terms of taxa but functions. Yet, which of the bacteria are responsible for which parts of the distributed metabolism and how they should be grouped together is insufficiently understood. An approach to map the different bacterial taxa that make up the gut microbiome onto the different functional niches of microbial carbohydrate fermentation have been described in the art (WO2022/023458). A presented approach uses in vitro measurements of bacterial growth and metabolic activity to identify which bacterial taxa are responsible for which metabolic function in the relevant complex context of whole human fecal microbiomes. Prebiotic compositions focusing on microbial functions which are key for the specific therapeutic target are known too (WO2020/079036). However, engraftment and stability of probiotic and prebiotic compositions in vivo are still not straightforward to achieve. Therefore, there is a need to design combinations of bacterial species and nutritional components which synergistically improve the colonization of the host’s microbiome, in order to prevent or treat intestinal dysbiosis and diseases or disorders related to detrimental conditions. SUMMARY OF THE INVENTION Here, the inventors identified ‘characteristic taxa’ for a panel of different carbon sources that are representative of the dietary components that are resistant to digestion by host enzymes. They then validated the predictive relevance of these characteristic taxa with data from a nutritional intervention study in humans. In a first aspect, the invention concerns a combination therapy comprising (i) at least one bacterial strain and (ii) at least one dietary fibre and/or carbohydrate source, wherein said combination therapy comprises: (a) at least one bacterial strain selected from the genera Lachnospira, UMGS1375, CAG-41, CAG-274 and UMGS1441, and (b) pectin (PE); (a) at least one bacterial strain selected from the genera Ruminococcus_D, Lachnospira, CAG-41, TF01-11, UMGS1441, Ruminiclostridium_E, Agathobacter, Acetatifactor and Kineothrix; and (b) pea fibre (PF); (a) at least one bacterial strain selected from the genera UMGS1375, Lachnospira, Olsenella_E, Murimonas, and Acetatifactor and (b) arabinogalactan (AG); (a) at least one bacterial strain selected from the genera UMGS1375, Acutalibacter, Parabacteroides, Fusicatenibacter, Clostridium_A, Eisenbergiella, Agathobacter, Murimonas and Ruminococcus_A; and (b) resistant dextrin (RD); (a) at least one bacterial strain selected from the genera Blautia_A, Agathobacter, Bifidobacterium, Fusicatenibacter, Acetatifactor, Murimonas; and (b) xylan (XY); (a) at least one bacterial strain selected from the genera UMGS1375, Akkermansia, Ruminococcus_E, GCA- 900066135, Eubacterium_G, Agathobacter, Barnesiella, Mediterraneibacter and CAG-45; and (b) mucin (MU); (a) at least one bacterial strain selected from the genera Anaerostipes, Parabacteroides, Phascolarctobacterium_A, Bacteroides and Phascolarctobacterium; and (b) yeast extract (YE); and/or (a) at least one bacterial strain selected from the genera Agathobacter, Roseburia, Coprococcus, CAG-45, Acetatifactor and Ruminococcus_E; and (b) soluble starch (SS). Preferably, the combination therapy comprises: (a) at least one bacterial strain selected from the group consisting of Acutalibacter timonensis, Acutalibacter sp003612555, Parabacteroides distasonis, Parabacteroides merdae, Fusicatenibacter saccharivorans, Clostridium_A leptum, Eisenbergiella sp900066775, Eisenbergiella massiliensis, Eisenbergiella tayi, UMGS1375 sp900066615, Agathobacter rectalis, Agathobacter faecis, Murimonas intestini, Ruminococcus_A sp000437095, Ruminococcus_A sp003011855; and (b) resistant dextrin (RD); (a) at least one bacterial strain selected from the group consisting of CAG-41 sp900066215, UMGS1441 sp900551755, Lachnospira eligens, Lachnospira rogosae, Lachnospira sp003451515, Lachnospira sp003537285, CAG-274 sp900545305 and UMGS1375 sp900066615 ; and (b) pectin (PE); (a) at least one bacterial strain selected from the group consisting of CAG-41 sp900066215, T