Causal association of gut microbiota with type 2 diabetes, type 1 diabetes and glycemic traits: a two-sample Mendelian randomization study

Purpose: Growing evidence from observational studies reveals that gut microbiota is associated with type 2 diabetes (T2D), type 1 diabetes (T1D) and glycemic traits. Aiming to comprehensively explore these causal relationships, we conducted a two-sample bidirectional Mendelian randomization (MR) analysis. Method We conducted a bidirectional two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) summary data. The gut microbiota-related GWAS data were obtained from the MiBioGen consortium, and the summary statistics for T2D and T1D from the GWAS database. Besides, the 3 glycemic traits (2h-glucose, fasting glucose, fasting insulin) summary statistics were all obtained from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). The selection of instrumental variables strictly conformed to a set of predefined inclusion and exclusion criteria. Inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode and simple mode were used to access the causal association. Several sensitivity analyses are used to ensure the robustness of the results. Results According to causal effect models with MR analysis, we identified 7 significant causal relationships between gut microbiota and diabetes (T2D/T1D) and glycemic traits, including phylum Verrucomicrobia , genus Actinomyces , family Veillonellaceae , class Melainabacteria , order Gastranaerophilales , family unknownfamily.id.1000001214 and phylum Proteobacteria . Evidence from multiple sensitivity analyses further supports these associations. Conclusions Our research revealed that gut microbiota was causally associated with diabetes (T2D/T1D) and glycemic traits and may provide fresh ideas for early detection and treatment.