Highlights on two decades with microbiota and inflammatory bowel disease from etiology to therapy

Abstract

Inflammatory Bowel diseases (IBDs) constitute a complex panel of disorders characterized with chronic inflammation affecting the alimentary canal along with extra intestinal manifestations. Its exact etiology is still unknown; however, it seems to be the result of uncharacterized environmental insults in the intestine and their immunological consequences along with dysbiosis, in genetically predisposed individuals. It was the main target of our team since 2002 to explore the etiology of IBD and the related role of bacteria. For almost two decades, our laboratory, among others, has been involved in the reciprocal interaction between the host gastrointestinal lining and the homing microbiota. In the first decade, the attention of scientists focused on the possible role of enteropathogenic E. coli and its relationship to the mechanistic pathways involved in IBD induced in both rats and mice by chemicals like Iodoacetamide, Dextran Sodium Sulfate, Trinitrobenzene, thus linking microbial alteration to IBD pathology. A thorough characterization of the various models was the focus of research in addition to exploring how to establish an active homeostatic composition of the commensal microbiota, including its wide diversity by restoration of gut microbiota by probiotics and moving from dysbiosis to eubiosis. In the last six years and in order to effectively translate such findings into clinical practice, it was critical to explore their relationship to colorectal cancer CRC both in solid tumors and chemically induced CRC. It was also critical to explore the degree of intestinal dysbiosis and linking to IBD, CRC and diabetes. Remarkably, the active mechanistic pathways were proposed as well as the role of microbiota or bacterial metabolites involved. This review covers two decades of investigations in our laboratory and sheds light on the different aspects of the relationship between microbiota and IBD with an emphasis on dysbiosis, probiotics and the multiple mechanistic pathways involved.