Gut microbiome and diabetic kidney disease: Insights from Mendelian randomization and genetic correlations.

The causal effects of specific gut microbiota (GM) on the development of diabetic kidney disease (DKD) have not yet been revealed. We employed independent single nucleotide polymorphisms from 196 gut bacterial taxa (N = 18,340) as instrumental variables in a 2-sample Mendelian randomization framework. DKD summary statistics were sourced from publicly accessible genome-wide association study databases, the FinnGen Consortium R9 publications, and the Juvenile Diabetes Research Foundation-funded collaborative research program. The analysis was conducted on outcome data from various sources using GM data as exposure. DKD outcomes from different sources were meta-analyzed based on 196 GM classifications. Furthermore, we evaluated the genetic association between specific GM populations and DKD by using the linkage disequilibrium score regression approach. Results showed Coprococcus2 (odds ratios [OR] = 0.8297, 95% confidence interval [CI]: 0.7427-0.9268, P = .0009) and Defluviitaleaceae (OR = 0.8802, 95% CI: 0.8121-0.9539, P = .0019) offer protection, while Bacteroidetes (OR = 1.1869, 95% CI: 1.0261-1.3729, P = .0211), Lachnoclostridium (OR = 1.1602, 95% CI: 1.0267-1.3111, P = .0172), and Veillonellaceae (OR = 1.0998, 95% CI: 1.0183-1.1879, P = .0154) increase risk. This study establishes a causal relationship between GM and DKD and highlights potential protective and risk-related microbial taxa.