title: Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice.
abstract: Studying host-microbiota interactions are fundamental to understanding the mechanisms involved in intestinal homeostasis and inflammation. In this work, we analyzed these interactions in mice that were mono-associated with six microorganisms that are representative of inflammatory bowel disease (IBD)-associated dysbiosis: the bacteria Bacteroides thetaiotaomicron, adhesive-invasive Escherichia coli (AIEC), Ruminococcus gnavus and Roseburia intestinalis; a yeast used as a probiotic drug, Saccharomyces boulardii CNCM I-745; and another yeast, Candida albicans. Extensive ex vivo analyses including colon transcriptomics, histology, immune response, bile acid metabolism and short-chain fatty acid production were studied. We showed that B. thetaiotaomicron had the highest impact on the immune system because it was almost able to recapitulate the effects of the entire conventional microbiota and notably induced Treg pathways. Furthermore, these analyses uncovered the effects of E. coli AIEC LF82 on indoleamine 2,3-dioxygenase expression and of S. boulardii CNCM I-745 on angiogenesis. These results were confirmed in vitro in human cell lines. Finally, our results suggested that R. gnavus has major effects on metabolism, and notably on tryptophan metabolism. This work therefore reveals that microorganisms with a potential role in intestinal homeostasis and inflammation have specific impacts on the host, and it suggests several tracks to follow to understand intestinal homeostasis and IBD pathogenesis better, providing new insights to identify novel therapeutic targets.
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Hoffmann
authors.affiliation: ILTOO Pharma, Institut du Cerveau et de Moelle Epinière, Hôpital Pitié Salpêtrière, Paris, France.
authors.forename: Hang-Phuong
authors.identifier: http://orcid.org/0000-0002-7896-7401
authors.initials: HP
authors.lastname: Pham
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Bridonneau
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Aubry
authors.affiliation: ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lamas
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Martin-Gallausiaux
authors.affiliation: INRA, UMR1313 GABI/CRB GADIE, Jouy en Josas, France.|AgroParisTech, UMR1313 GABI, Jouy en Josas, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Moroldo
authors.affiliation: ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Rainteau
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lapaque
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, INSERM UMR_S 959, CNRS FRE 3632, Immunology, Immunopathology, Immunotherapy (I3), Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Six
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Mathias L
authors.initials: ML
authors.lastname: Richard
authors.affiliation: Biocodex, Centre Recherche et Développement, Compiègne, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Fargier
authors.affiliation: Biocodex, Centre Recherche et Développement, Compiègne, France.
authors.forename: Marie-Emmanuelle
authors.initials: ME
authors.lastname: Le Guern
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Langella
authors.affiliation: INRA, UMR1319 MICALIS, Jouy en Josas, France.|AgroParisTech, UMR1319 MICALIS, Jouy en Josas, France.|ERL INSERM U 1157/UMR7203, Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie (UPMC), Paris, France.|AgroParisTech, UMR1313 GABI, Jouy en Josas, France.|Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris et Université Paris 6, Paris, France.
authors.forename: Harry
authors.initials: H
authors.lastname: Sokol
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D003106:Colon / Q000382:microbiology; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000382:microbiology*; D000069196:Gastrointestinal Microbiome; D005856:Germ-Free Life; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D015003:Yeasts / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification