Abstract
BACKGROUND: To clarify the causal relationship between gut microbiota and diabetic nephropathy (DN), we employed Mendelian randomization (MR). Despite a strong correlation observed, establishing causality is still unclear. By utilizing MR, we aimed to investigate this relationship further and shed light on the potential causal effect of gut microbiota on DN. METHODS: Genetic instrumental variables for gut microbiota were obtained from a GWAS with 18340 participants. DN summary statistics (1032 cases, 451248 controls) were sourced from a separate GWAS. The primary analysis used the inverse-variance weighted (IVW) method. Reverse MR analysis was conducted to explore reverse causation. Rigorous sensitivity analyses were performed to ensure the resilience and reliability of the study's findings. RESULTS: We found two bacterial traits associated with an increased risk of DN: genus LachnospiraceaeUCG008 (OR: 1.4210; 95% CI: 1.0450, 1.9322; p = 0.0250) and genus Terrisporobacter (OR: 1.9716; 95% CI: 1.2040, 3.2285; p = 0.0070). Additionally, phylum Proteobacteria (OR: 0.4394; 95% CI: 0.2721, 0.7096; p = 0.0008) and genus Dialister (OR: 0.4841; 95% CI: 0.3171, 0.7390; p = 0.0008) were protective against DN. Sensitivity analyses consistently supported these results. In the reverse MR analysis, no statistically significant associations were observed between DN and these four bacterial traits. CONCLUSIONS: Our analyses confirmed a potential causal relationship between certain gut microbiota taxa and the risk of DN. However, additional studies are required to elucidate the underlying mechanisms through which gut microbiota influences the development of DN.