Investigating gut microbiome and mucin O-glycan interactions in mice with colorectal cancer
Metformin and intermittent fasting have been associated with lower colorectal cancer incidence, potentially through their effects on host molecular mechanisms. Accumulating evidence suggests a role of the gut microbiome in their anti-cancer effects, however, there is a lack of direct examinations, particularly encompassing the mucosal-adhered microbiota and colon mucus O-glycosylation. The aim of this research is to determine how metformin, intermittent fasting and a combination of both treatments alter the fecal and mucosal microbiome and O-glycosylation of colon mucin in mice with chemically induced colorectal cancer. Correlation network analysis was used to identify associations between specific gut bacteria and mucin O-glycan structures. All three treatments produced significant and distinct changes to fecal and mucosal microbial communities. Treatment specific microbiome changes were observed, encompassing reductions in the relative abundance of colorectal cancer-associated bacteria. All treatments produced significant changes in relative abundance of O-glycan structures, with significant correlations identified between O-glycan structures and gut bacteria with established associations to colon cancer. This thesis reports on the first analysis of mucosal-bound microbiota, mucin O-glycan changes and their correlations in metformin and fasting treated mice that were at risk of developing colorectal cancer.