1173-P: Therapeutic Response to Metformin Monotherapy in Type 2 Diabetes Is Associated with Butyrate-Producing Gut Microbiota

Type 2 diabetes is the fifth leading cause of death in Taiwan. The metabolic derangements in type 2 diabetes have been attributed to the compositional changes of the gut microbiota. Metformin, as the first-line treatment for type 2 diabetes, has been found to exert its antidiabetic actions through modulations of the gut microbiota. However, to our knowledge, no literature reported the associations between the therapeutic response to metformin monotherapy and the compositions of the gut microbiota. Thus, we hypothesized that the compositions of gut microbiota differ in type 2 diabetes with failure and success of metformin monotherapy. We had recruited 381 type 2 diabetes diagnosed for more than two years in a university hospital. Then based on medical records, we identified 12 subjects as the metformin-failure group and 14 as the metformin-success group, who maintained HbA1C>7% with not only metformin or with metformin monotherapy, respectively. We collected the biochemical data and analyzed the gut microbiota by Illumina sequencing of 16S rRNA gene. The result showed that while the two groups having similar clinical characteristics, the gut microbiota were significantly different by principal coordinates analysis. In addition, the metformin-success group had decreased richness and evenness. Furthermore, butyrate-producing gut microbiota including Butyrivibrio and Blautia producta increased in the metformin-success group. The short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, are produced by gut microbiota. The imbalance in the ratio of the SCFAs, such as decrease in butyrate and increase in acetate, leads to metabolic derangements in type 2 diabetes. Our finding showed that the metformin-success group were associated with butyrate-producing gut microbiota. In conclusion, the gut microbiota that can reverse the imbalance of SCFAs might be the key for diabetes to have sustained metabolic benefits with metformin monotherapy. Disclosure W. Hung: None. W. Hung: None. Funding Kaohsiung Medical University