Exploring the potential link between gut microbiota and chronic kidney disease in causality: A 2-sample Mendelian randomization study

Abstract

Increasing evidence indicates a significant correlation between gut microbiota (GM) and susceptibility to chronic kidney disease (CKD). However, causal relationship presence remains uncertain. Mendelian randomization (MR) was applied to evaluate potential causal relation from GM to CKD. Genomic association analysis aggregates publicly online databases, utilizing Genome-Wide Association Study (GWAS) database focused on GM and CKD. For examination of potential causal connection from GM to CKD, a 2-way, 2-sample Mendelian randomization (MR) method was applied. Sensitivity analyses were utilized to scrutinize for heterogeneity, horizontal pleiotropy, MR outcomes resilience. Result from inverse variance weighting (IVW) method revealed that 10 microbiotas such as Porphyromonadaceae (OR=1.351, 95% CI: 1.114-1.638, P=.002), Dorea (OR=1.236, 95% CI: 1.040-1.468, P=.016), Ruminococcus torques group (OR=1.290, 95% CI: 1.035-1.608, P=.024) are potential CKD risk factors. Five microbiotas, including the Prevotellaceae (OR=0.814, 95% CI: 0.719-0.922, P=.001) are potential CKD protective factors. Sensitivity analyses reveal no horizontal pleiotropy or heterogeneity. Additionally, reverse MR results unveiled potential relation between CKD and disorders in 3 microbiotas, including Senegalimassilia. According to the investigation, MR method was employed to delve into reciprocal causal connection from GM to CKD. Our findings identified 15 types of GM causally linked to CKD, as well as CKD demonstrating causal associations with 3 types of GM. Further exploration of these associated GM types is hopeful to raise novel insights, for CKD preventing and early monitoring.