Xixi Song,1,2 Jingqiu Cui,1 Shiwei Li,1 Bo Huang1 

1Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Endocrinology and Metabolism, Baoding No.1 Central Hospital, Baoding, People’s Republic of China

Correspondence: Jingqiu Cui, Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, No. 154 Anshan Dao, Heping District, Tianjin, 300052, People’s Republic of China, Tel +8613920765604, Email cuijingqiu@tmu.edu.cn

Background:  Previous studies have established a correlation between gut microbiota, metabolites, and diabetic nephropathy (DN). However, the inherent limitations of observational studies, including reverse causality and confounding factors, made this relationship uncertain.
Methods: In this study, we compiled summary statistics from a genome-wide association study (GWAS) conducted on gut microbiota, metabolites, and DN. We employed a two-sample Mendelian randomization (MR) approach, utilizing inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods.
Results:  We detected the protective nature of genetically predicted representatives from the family Bacteroidaceae (OR: 0.716, 95% CI: 0.516– 0.995, p = 0.046), family Victivallaceae (OR: 0.871, 95% CI: 0.772– 0.982, p = 0.026), genus Bacteroides (OR: 0.716, 95% CI: 0.516– 0.995, p = 0.046), genus Coprococcus 2 (OR: 0.745, 95% CI: 0.576– 0.963, p = 0.025), and genus Lactococcus (OR: 0.851, 95% CI: 0.730– 0.992, p = 0.039) against the development of DN. Conversely, we identified a positive correlation between the incidence of DN and entities, such as Phylum Bacteroidetes (OR: 1.427, 95% CI: 1.085– 1.875, p = 0.011), class Bacteroidia (OR: 1.304, 95% CI: 1.036– 1.641,p = 0.024), order Bacteroidales (OR: 1.304, 95% CI: 1.035– 1.641, p = 0.028), genus Catenibacterium (OR: 1.312, 95% CI: 1.079– 1.594, p = 0.006), genus Lachnoclostridium (OR: 1.434, 95% CI: 1.129– 1.821, p = 0.003), and genus Parasutterella (OR: 1.270, 95% CI: 1.070– 1.510, p = 0.006). In our analysis, none of the gut metabolites demonstrated a causal relationship with DN.
Conclusion:  Our results substantiated the potential causal association between specific gut microbiota and DN. Therefore, our study offers novel insight into the mechanisms underlying DN. This finding provides a theoretical foundation for the future development of targeted strategies for the prevention and treatment of DN.

Keywords: Gut microbiota, diabetic nephropathy, gut metabolites, Mendelian randomization