Investigating the effect of metformin on the gut microbiome and glycome in colorectal cancer

Colorectal cancer (CRC) is the second deadliest cancer worldwide, with a survival rate of 13% when diagnosed in the advanced stages. Preventing the development and progression of CRC is integral to reducing its high mortality rates. Hallmarks of colorectal neoplasia include progressive alterations of the gut microbiome and glycosylation of mucin proteins lining the colon. Recent epidemiological studies reported reduced CRC incidence in patients undergoing metformin treatment for type 2 diabetes, however, mechanisms behind metformin’s anti-CRC activities are yet to be defined. Current literature suggests that the gut microbiome may contribute to metformin’s efficacy against CRC. While bidirectional interactions between gut microbes and colonic mucin O-glycans are known to shape the microbiome composition, the link between metformin, gut microbes, mucosal O-glycosylation, and CRC prevention is yet to be determined. Using male and female mice with chemically induced colorectal neoplasia, this study examined metformin’s chemopreventative effects and its impact on the gut microbiome and colonic mucin O-glycosylation. Distinct differences were observed in both the gut microbiome and the O-glycome between cancer-induced and untreated mice. Metformin treatment was found to have a limited impact on cancer incidence, the gut microbiome, and mucin O-glycosylation.