Mendelian randomization analysis of gut microbiota and chronic kidney disease: Implications for herbal interventions

Abstract

Based on the gut-kidney axis theory and using Mendelian randomization (MR), this study investigated the potential causal relationship between gut microbiota and chronic kidney disease (CKD), and explored candidate Chinese herbal medicines (CHM) that may treat gut microbiota for CKD management. Genome-wide association study summary statistics of gut microbiota and CKD were obtained from the NHGRI-EBI genome-wide association study Catalog and FinnGen database. MR analyses were performed in R using inverse variance weighted as the main method, supplemented by heterogeneity and pleiotropy tests. Single-nucleotide polymorphisms were mapped to nearby genes, followed by enrichment analyses and prediction of potential CHM. MR analysis identified 6 gut microbiota taxa associated with CKD risk. Functional analyses suggested the involvement of immune- and inflammation-related pathways. A set of candidate CHM were predicted, aligning with the therapeutic principles of reinforcing healthy Qi and eliminating pathogens. This study identified gut microbiota taxa with potential causal roles in CKD and predicts candidate herbal medicines for further validation.

Keywords: Chinese herbal medicine prediction; Mendelian randomization; causal relationship; chronic kidney disease; gut microbiota; gut-kidney axis; reverse network pharmacology.