Causal Relationships Between Gut Microbiota, Metabolites, and Diabetic Nephropathy: Insights from a Two-Sample...

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.

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.

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.

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.