The influence of gut microbiota on membranous nephropathy: A two-sample Mendelian randomization study

Background: Therapeutic approaches that target the gut microbiota may be helpful in the potential prevention and treatment of membranous nephropathy (MN). Several studies demonstrated a correlation between gut microbiota and MN. However, the confounding evidence cannot prove a causal relationship between gut microbiota and MN. Materials and methods: The aim of our study is to assess genomewide association study data for a causal relationship between gut microbiota and MN using a two-sample Mendelian randomization (MR) approach. Inverse variance weighted (IVW) was used as the primary technique to determine the association of genetic variants from gut microbiota and MN patients. Besides, sensitivity analyses confirmed the accuracy of the results. Finally, we applied false discovery rate (FDR) correction to results with IVW < 0.05 during multiple hypothesis testing. Results: The results from IVW estimates indicated that Bacillales exhibited a significant association with MN, acting as a risk factor (OR = 1.52, 95% CI: 1.14 - 2.02, p = 0.005). In addition, our univariable MR results showed that 7 bacterial taxa ( Melainabacteria, Butyricicoccus, Catenibacterium, Ruminiclostridium5, RuminococcaceaeUCG003, RuminococcaceaeUCG013, and Gastranaerophilales) had suggestive associations with MN. The sensitivity analysis did not reveal any significant heterogeneity in the instrumental variables or horizontal pleiotropy. Conclusion: Our findings provided causal evidence for the effect of gut microbiota on MN patients and broadened the spectrum of bacterial taxa that might be involved in the pathogenesis of MN. These selected bacterial taxa hold promise as new biomarkers, which may aid in designing targeted therapeutic modalities for MN, improving our comprehension of the gut-kidney axis.