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

• DOI: 10.2337/dc16-1324
• Publication Date: 2016-11-15T02:25:21Z
• Authors: Jacobo de la Cues...; Noel T. Mueller; Vanessa Corrales-...; Eliana P. Velásqu...; Jenny A. Carmona; José M. Abad; Juan S. Escobar
• Keywords: Adult; Male; 0301 basic medicine; 2. Zero hunger; Adolescent; Mucins; Colombia; Middle Aged; Fatty Acids, Volatile; 16. Peace & justice; Metformin; Gastrointestinal Microbiome; 3. Good health; Feces; 03 medical and health sciences; Diabetes Mellitus, Type 2; Verrucomicrobia; Case-Control Studies; RNA, Ribosomal, 16S; Humans; Hypoglycemic Agents; Female

OBJECTIVE 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. On the basis of previous research, we hypothesized that metformin is associated with higher levels of short-chain fatty acid (SCFA)–producing and mucin-degrading microbiota.

RESEARCH DESIGN AND METHODS 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 measured demographic information, anthropometry, and blood biochemical parameters and collected fecal samples from which we performed 16S rRNA gene sequencing to analyze the composition and structure of the gut microbiota.

RESULTS 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 an operational taxonomic unit of Prevotella. In contrast, compared with participants without diabetes, participants with diabetes not taking metformin had higher relative abundance of Clostridiaceae 02d06 and a distinct operational taxonomic unit of Prevotella and a lower abundance of Enterococcus casseliflavus.

CONCLUSIONS Our results support the hypothesis that metformin shifts gut microbiota composition through the enrichment of mucin-degrading A. muciniphila as well as several SCFA-producing microbiota. Future studies are needed to determine if these shifts mediate metformin’s glycemic and anti-inflammatory properties.