Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

Abstract

The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars' attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota-CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.

Keywords: Colorectal cancer; Gut microbiota; Metformin; Type 2 diabetes mellitus.

Figure 1

The potential metformin-gut microbiota-colorectal cancer axis in type 2 diabetes mellitus. (1) Metformin may change the gut microbiota after entering the intestine. The changed gut microbiota has cascade reactions to affect tumorigenesis, including reducing inflammation, regulating immunity, and producing metabolites, such as bile acid and genetic toxins. (2) Metformin may play a pharmacological role to influence cancer-related systems in colorectal epithelial cells in the presence of gut microbiota. CDT: Cytolethal distending toxin; SCFAs: Short-chain fatty acids.