Cross-talk between microbiota and immune responses in inflammatory bowel disease

The dissertation entitled ‘cross-talk between microbiota and immune responses in inflammatory bowel disease’ discusses and explores the role of microbiome, microbial-derived products, and immune responses contributing to the pathophysiology of inflammatory bowel disease (IBD). At first, the dissertation describes the various tools developed to study intestinal physiology and function in health and disease. In addition, we highlighted the use of gut-on-chip model with mouse intestinal tissue for the first time. In the next two chapters, the role of the microbiome and mycobiome in IBD was investigated. We studied the effects of curdlan (a bacterial-derived-β-glucans) on the microbiome and the subsequent effect on inflammation in an experimental colitis model, namely DSS colitis in mice. Curdlan was shown to enhance bifidobacteria presence in the colon and resulted in less severe inflammation in mice. Besides changes in the bacterial composition, we studied the role of fungi (mycobiome) in human fecal microbiota transfer (FMT). We demonstrated Filobasidium genus as a potential biomarker associated with positive response to FMT in ulcerative colitis patients. We further showed the potential of Filobasidium spp. to elicit immune responses in human monocyte-derived macrophages. Next, we explored the immune responses elicited through microRNA’s, particularly miR-511 in different colitis models in mice. We showed that miR-511 deficiency ameliorated inflammation in a DSS colitis model through toll-like receptor (TLR)-3 and 4 regulation. However, in the T cell transfer colitis model, miR-511 deficiency resulted in worsening intestinal inflammation. Through these two colitis models, we suggested the role played by miR-511 in the regulation of intestinal inflammation.