Assessing the causal relationship between gut microbiota and diabetic nephropathy: insights from two-sample Mendelian randomization.

Abstract

The causal association between gut microbiota (GM) and the development of diabetic nephropathy (DN) remains uncertain. We sought to explore this potential association using two-sample Mendelian randomization (MR) analysis. Genome-wide association study (GWAS) data for GM were obtained from the MiBioGen consortium. GWAS data for DN and related phenotypes were collected from the FinngenR9 and CKDGen databases. The inverse variance weighted (IVW) model was used as the primary analysis model, supplemented by various sensitivity analyses. Heterogeneity was assessed using Cochran's Q test, while horizontal pleiotropy was evaluated through MR-Egger regression and the MR-PRESSO global test. Reverse MR analysis was conducted to identify any reverse causal effects. Our analysis identified twenty-five bacterial taxa that have a causal association with DN and its related phenotypes (p < 0.05). Among them, only the g_Eubacterium_coprostanoligenes_group showed a significant causal association with type 1 DN (p < Bonferroni-adjusted p-value). Our findings remained consistent regardless of the analytical approach used, with all methods indicating the same direction of effect. No evidence of heterogeneity or horizontal pleiotropy was observed. Reverse MR analysis did not reveal any causal associations. This study established a causal association between specific GM and DN. Our findings contribute to current understanding of the role of GM in the development of DN, offering potential insights for the prevention and treatment strategies for this condition.