The gastro-intestinal tract is a complex milieu in which coexist host epithelial and immune cells, a wide array of microorganisms and food antigens. The intestinal microbiota is notably composed of trillions of bacteria, which are strikingly well tolerated by the host, whereas pathogenic microorganisms are recognized and eradicated by the immune system. The mechanisms involved in the distinction between harmful and symbiotic microorganisms remain unclear. In some circumstances, the tolerance toward the intestinal microbiota is broken, leading to inappropriate immune response and intestinal or extra-intestinal inflammation. This is the case in inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis, but possibly also in extra intestinal immune mediated diseases such as rheumatoid arthritis, multiple sclerosis or type1 diabetes. CD and UC are characterized by chronic and relapsing inflammation of the gastrointestinal tract. Their socio-economic issues are important because they affect young subjects and their incidence and prevalence are relatively high in industrialized countries. The exact pathogenesis of CD and UC are still unknown but involves a dysregulated immune response toward the gut microbiota in genetically predisposed host. In IBD a deviation of the gut microbiota composition called dysbiosis has been repeatedly pointed out. Concomitantly, genetic studies, and notably genome wide association studies, have identified several susceptibility loci in genes involved in the interaction with microorganisms.
The aim of the lab is to decipher the mechanisms involved in the complex cross-talk between the gut microbiota and the host in health, and its alterations leading to human diseases such as IBD.
From the left: Marie-Laure Michel, Mathias Lavie-Richard, Allison Agus, Chantal Bridonneau, Sarah Jegou, Bruno Sovran, Harry Sokol, Louise Dupraz, Jérémy Glodt, Marjolène Straube, Grégory Da Costa et Julien Planchais
Selected publications :
Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermúdez-Humarán LG, Gratadoux JJ, Blugeon S, Bridonneau C, Furet JP, Corthier G, Grangette C, Vasquez N, Pochart P, Trugnan G, Thomas G, Blottière HM, Doré J, Marteau Ph, Seksik Ph, Langella Ph. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn's disease patients. Proc Natl Acad Sci U S A 2008; 105(43):16731-36
Sokol H, Conway KL, Zhang M, Choi M, Morin B, Cao Z, Villablanca EJ, Li C, Wijmenga C, Yun SH, Shi HN, Xavier RJ. Card9 Mediates Intestinal Epithelial Cell Restitution, T-helper 17 Responses, and Control of Bacterial Infection in Mice. Gastroenterology. 2013 Sep;145(3):591-601
Quévrain E, Maubert MA, Michon C, Chain F, Marquant R, Tailhades J, Miquel S, Carlier L, Bermúdez-Humarán LG, Pigneur B, Lequin O, Kharrat P, Thomas G, Rainteau D, Aubry C, Breyner N, Afonso C, Lavielle S, Grill JP, Chassaing G, Chatel JM, Trugnan G, Xavier R, Langella P,Sokol H*, Seksik P*(*:equally contributors) Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease. Gut. 2016 Mar;65(3):415-25
Sokol H, Leducq V, Aschard H, Pham HP, Jegou S, Landman C, Cohen D, Liguori G, Bourrier A, Nion-Larmurier I, Cosnes J, Seksik P, Langella P, Skurnik D, Richard ML, Beaugerie L. Fungal microbiota dysbiosis in IBD. Gut. 2016 [Epub ahead of print]
Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ and Sokol H. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nature Medicine 2016. Jun;22(6):598-605