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About us

The research unit M2iSH (Microbe, Intestine, Inflammation and Host Susceptibility), UMR 1071 Inserm/University of Clermont Auvergne/USC 1382 INRAE, is is a joint research unit between Inserm, INRAE ​​and University of Clermont Auvergne (UCA).

This M2iSH unit is a single team consists of about 60 people, 34 permanent staff, with Mathilde Bonnet (UCA) as Unit Director (DU) and Hang Nguyen (Inserm) as Vice Unit Director (DUA). The academic-researchers of this unit belong to 3 components (University institute of technology (IUT), Faculty of Medicine and Faculty of Pharmacy). The teaching hospital of Clermont-Ferrand, France, is also fully involved in this unit with the integration of the clinicians from Gastroenterology, Digestive Surgery and Internal Medicine departments. The presence of young physicians performing PhD program in our laboratory allows the development of translational research projects. Our research unit has been obtained Inserm label in 2012 and is also "Unit Under Contract" of INRAE (USC-1382) since 2005.

History

In 1994, Pr. Arlette Darfeuille-Michaud created and led a research group named "Intestinal Bacterial Pathogenesis" in the bacteriology laboratory of Medicine and Pharmacy Faculties EA3844, successively headed by Pr. J. Cluzel, J. Sirot and C. Forestier. This research unit has focuses on the infectious etiology of chronic inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis, which represent a real public health problem in industrialized countries. This research group focused on the infectious pathway of chronic inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis, which represent a real public health problem in industrialized countries. Showing for the first time in 1998 that the ileal mucosa of CD patients was abnormally colonized by Escherichia coli, our research group quickly gained international recognition in the field of microorganisms’ role in the etiology of CD. Our work led to the discovery in 1999 of a new pathovar which we designated AIEC for "Adherent-Invasive E. coli", a new group of pathogenic E. coli associated with CD. In 2004, we showed a high prevalence of patients, up to 35%, harboring these bacteria in a French cohort. These results were confirmed by several research groups around the world using different cohorts, and our research team was a pioneer in the discovery of these AIEC strains colonizing the intestinal mucosa of CD patients. These works allowed us to obtain the label JE2526 Young Team entitled "Evolution of pathogenic bacteria and host genetic susceptibility" in 2008.


The 2008-2011 periods was a step towards the Inserm labeling. In patients with ileal CD, we have shown overexpression of CEACAM5 and CEACAM6 molecules. CEACAM6 acts as a receptor for type 1 pili expressed by AIEC bacteria that abnormally colonize the ileal mucosa of CD patients by interacting with exposed mannose residues on the glycoprotein CEACAM6. This work is the subject of a patent that has led to several cooperation agreements with industrial partners to develop new therapeutic strategies targeting this interaction. During this period, we also showed the key role played by autophagy process in controlling the proliferation of AIEC bacteria in the intestinal epithelial cells or macrophages. In addition, patients with IBD are at high risk of developing colorectal cancer (CRC). Thus, in parallel with our studies on infectious etiology in CD, we have studied whether such a mechanism is involved in the CRC etiology in collaboration with physicians from “Surgery and Digestive Oncology” department of teaching hospital in Clermont-Ferrand.