Causal Relationship Between Metformin and the Abundance of Ten Intestinal Genera-Level Bacterial Populations: A Mendelian Randomization Analysis

ObjectiveThis study aims to investigate the causal effects of metformin on the abundance of 10 gut bacteria genera using Mendelian randomization(MR) analysis. The genera examined include Parabacteroides, Bacteroides, Alistipes, Adlercreutzia, Anaerofilum, Oxalobacter, Ruminococcaceae UCG003, Ruminococcus1, Butyrivibrio, and Eubacterium oxidoreducens group. MethodsData from public databases were utilized, with metformin as the exposure variable and the abundance of the 10 gut bacteria genera as outcome variables. An inverse variance-weighted method was employed for MR analysis to assess the causal effects of metformin on gut bacterial abundance using genetic instrumental variables. ResultsThe analysis revealed significant causal associations between metformin and the abundance of multiple gut bacteria genera. Specifically, metformin was positively correlated with Parabacteroides, Bacteroides, Alistipes, Adlercreutzia, Anaerofilum, Oxalobacter, Ruminococcaceae UCG003, and Ruminococcus1. Conversely, metformin was negatively correlated with Butyrivibrio and Eubacterium oxidoreducens group. These findings suggest that metformin may exert its pharmacological effects by modulating the abundance of gut bacteria. ConclusionsThere are significant causal associations between metformin and the abundance of multiple gut bacteria genera, indicating that the gut microbiota may be an important target for the pharmacological effects of metformin. This discovery provides new insights for further research into the mechanisms of metformin and the relationship between the gut microbiota and diseases.