Causal relationship between gut microbiota and type 2 diabetes: a two-sample Mendelian randomization study

Abstract

BackgroundStudies showed that development of gut microbial dysbiosis has a close association with type 2 diabetes (T2D). It is not yet clear if there is a causal relationship between gut microbiota and T2D.MethodsThe data collected from the published genome-wide association studies (GWASs) on gut microbiota and T2D were analyzed. Two-sample Mendelian randomization (MR) analyses were performed to identify causal relationship between bacterial taxa and T2D. Significant bacterial taxa were further analyzed. To confirm the findings’ robustness, we performed sensitivity, heterogeneity, and pleiotropy analyses. A reverse MR analysis was also performed to check for potential reverse causation.ResultsBy combining the findings of all the MR steps, we identified six causal bacterial taxa, namely, Lachnoclostridium, Oscillospira, Roseburia, Ruminococcaceae UCG003, Ruminococcaceae UCG010 and Streptococcus. The risk of T2D might be positively associated with a high relative abundance of Lachnoclostridium, Roseburia and Streptococcus but negatively associated with Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010. The results of MR analyses revealed that there were causal relationships between the six different genera and T2D. And the reverse MR analysis did not reveal any evidence of a reverse causality.ConclusionThis study implied that Lachnoclostridium, Roseburia and Streptococcus might have anti-protective effect on T2D, whereas Oscillospira, Ruminococcaceae UCG003 and Ruminococcaceae UCG010 genera might have protective effect on T2D. Our study revealed that there was a causal relationship between specific gut microbiota genera and T2D.