Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice

Thomas W Hoffmann (1) , Hang-Phuong Pham (2) , Chantal Bridonneau (1) , Camille Aubry (1) , Bruno Lamas (3) , Camille Martin-Gallausiaux (1) , Marco Moroldo (4) , Dominique Rainteau (5) , Nicolas Lapaque (1, 6) , Adrien Six (7) , Mathias L Richard (1) , Emilie Fargier (8) , Marie-Emmanuelle Le Guern , Philippe Langella (1) , Harry Sokol (1, 5, 9)

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
2 ICM - Institut du Cerveau = Paris Brain Institute
3 LBM UMR 7203 - Laboratoire des biomolécules
4 GABI - Génétique Animale et Biologie Intégrative
5 LBM-E4 - Microorganismes, Molécules Bioactives et Physiopathologie Intestinale
6 AgroParisTech
7 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
8 PAVE - INH : Pathologie végétale : biodiversité, écologie, interactions bioagresseurs-plantes
9 CHU Saint-Antoine [AP-HP]

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.

Domaines: Hépatologie et Gastroentérologie; Génomique, Transcriptomique et Protéomique [q-bio.GN]; Immunité adaptative; Bactériologie; Mycologie

Thomas W Hoffmann, Hang-Phuong Pham, Chantal Bridonneau, Camille Aubry, Bruno Lamas, et al.. Microorganisms linked to inflammatory bowel disease-associated dysbiosis differentially impact host physiology in gnotobiotic mice. The International Society of Microbiologial Ecology Journal, 2016, 10 (2), pp.460-477. ⟨10.1038/ismej.2015.127⟩. ⟨hal-01303788⟩