Posted May 3 , 2017 01:27 PM

Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid–Producing Microbiota in the Gut

de la Cuesta-Zuluaga J, et al. Diabetes Care 2017 Jan; 40 (1): 54-62

What were the findings (excerpted from the Abstract)?

Recent studies suggest the beneficial effects of metformin on glucose metabolism may be microbially mediated. We examined the association of type 2 diabetes, metformin, and gut microbiota in community-dwelling Colombian adults. Based on previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)–producing and mucin-degrading microbiota. Participants were selected from a larger cohort of 459 participants. The present analyses focus on the 28 participants diagnosed with diabetes; 14 taking metformin and the 84 participants without diabetes who were matched (3-to-1) to participants with diabetes by sex, age, and BMI. We collected demographic information, anthropometry, and blood biochemical parameters and also collected fecal samples from which we performed 16S rRNA gene sequencing to analyze the composition and structure of the gut microbiota. We found an association between diabetes and gut microbiota that was modified by metformin use. Compared with participants without diabetes, participants with diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and some varieties of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06, different varieties of Prevotella and lower abundance of Enterococcus casseliflavus.

Why is this important?

The development of type 2 diabetes, a disease rising in prevalence around the globe, has been linked in non-human and human studies to imbalances in microbiota of the intestinal tract (gut). In a past “Article of the Week” [October 14, 2015] researchers proposed that the major effect of metformin was in the gut, based on studies of a sustained-release form of metformin. This study provides evidence consistent with previous literature that the association between gut microbiota and type 2 diabetes is modified by metformin, and that metformin shifts gut microbiota composition through the enrichment of A. muciniphila, a mucin-degrading bacteria that has been shown to reverse several metabolic disorders, as well as several SCFA-producing microbiota. While further study is needed, it is provocative to ask whether these changes in gut microbiology play a role in the mechanism of action of glucose-lowering and/or the anti-inflammatory properties of metformin.

Read the Abstract: