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. 2025;28(6):1026-1038.
doi: 10.2174/0113862073311197240425073859.

Exploring the Causal Effects of Gut Microbiota on Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study

Kai Chen  1   2 , Xu Wang  1   2 , Zhihao Shang  1   2 , Qingyue Li  1   2 , Wenqiang Yao  1   2 , Shaobo Guo  1   2 , Yingting Guan  1   2
Affiliations

Exploring the Causal Effects of Gut Microbiota on Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study

Kai Chen et al. Comb Chem High Throughput Screen. 2025.

Abstract

Background: In recent years, an increasing number of studies have indicated a bidirectional relationship between gut microbiota and the kidneys (the gut-kidney axis). Currently, the potential causal relationship between gut microbiota and diabetic nephropathy remains unclear. This study explores the causal effects of gut microbiota on diabetic nephropathy through Mendelian randomization.

Methods: We carried out a comprehensive Mendelian Randomization (MR) analysis, drawing on the Genome-wide Association Study (GWAS) data for 196 varieties of gut microbiota and diabetic nephropathy. The primary analytical approach employed was the inverse-variance weighted, supplemented by the MR-Egger, weighted median, simple mode, and weighted mode. We rigorously assessed heterogeneity with Cochran's Q test and examined pleiotropy via MREgger intercept and MR-PRESSO tests. To ensure the reliability of our findings, we conducted funnel plots and leave-one-out analysis.

Results: Our study indicates a causal relationship between the increased risk of diabetic nephropathy and specific gut microbiota, including the Bacteroidia (P=0.01892; OR=1.593; 95%CI, 1.080-2.350), Bacteroidales (P=0.01892; OR=1.593; 95% CI, 1.080-2.350), and LachnospiraceaeUCG008 (P=0.01350; OR=1.452; 95% CI, 1.080-1.953). Conversely, potential protective factors include the Proteobacteria (P=0.00397; OR=0.528; 95% CI, 0.342-0.815), Gammaproteobacteria (P=0.00965; OR=0.474; 95% CI, 0.270-0.834), Lentisphaeria (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), Victivallales (P=0.04417; OR=0.756; 95% CI, 0.576-0.993), and Dialister (P=0.00118; OR=0.513; 95%CI, 0.343-0.768).

Conclusion: This study confirms the causal effects of gut microbiota on diabetic nephropathy. Identifying the risk and protective factors within the gut microbiota for diabetic nephropathy offers fresh insights and novel approaches for preventing and treating this condition.

Keywords: Gut microbiota; causal effects; diabetic nephropathy; genome-wide association study; mendelian randomization; protective factors.; risk factors.

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