The Effects of Metformin on the Gut Microbiota of Patients with Type 2 Diabetes: A Two-Center, Quasi-Experimental Study.

ABSTRACT

Metformin is reported to affect human gut microbiota; however, the nature of this association in Japanese patients with type 2 diabetes mellitus (T2DM) is unknown. We enrolled 31 patients with T2DM who took metformin for the first time in this study. We compared them before and after four weeks of taking metformin. Fecal samples were collected and 16S rDNA sequences were performed to identify the gut microbiota. Blood samples and Gastrointestinal Symptom Rating Scale (GSRS) questionnaire results, denoting gastro-intestinal symptoms, were also collected. In the whole-group analysis, no significant differences were found at the phylum level. In a subgroup of 21 patients that excluding those using medications affecting gut microbiota, there was a significant decrease of the phylum Firmicutes (p = 0.042) and of the ratio of the Firmicutes and Bacteroidetes abundances (p = 0.04) after taking metformin. Changes in abdominal pain (r = -0.56, p = 0.008) and regurgitation (r = -0.53, p = 0.01) were associated with Parabacteroides. Despite there being no direct association with abdominal symptoms, our study revealed that the composition of gut microbiota in Japanese individuals with T2DM partially changed after starting metformin.