Impact of metformin on the gut microbiome of mouse colorectal cancer models

Metformin, which is an antidiabetic drug, has been shown to inhibit colorectal cancer (CRC). While the mechanisms underpinning the anti-CRC effects of metformin are largely unknown, the gut microbiome is thought to play a role in mediating them. Here, we examined the impact of metformin and CRC induction on the gut microbiome and host physiology of C57BL/6J mice chemically induced to develop CRC via three protocols: azoxymethane (AOM), dextran sulphate sodium (DSS) and a combination of AOM and DSS. 

Histological analysis of the colon revealed first-grade dysplasia in the AOM group, whereas the AOM group with metformin lacked this abnormality, showing a protective effect of metformin against the primary stages of CRC. No such effects of metformin were observed in DSS and AOM-DSS-treated mice. Significant shifts were seen in the microbial community structure and composition between groups with and without metformin addition, where the relative abundance of Akkermansiaceae, Lactobacillaceae, and Rikenellaceae families was higher in all metformin-treated groups. Apart from these clear metformin-associated changes in the gut microbiome and host physiology, we also observed distinct impacts of the three CRC induction protocols on the gut microbiome and the exact impact of metformin on the gut microbiome was CRC induction protocol specific.