Investigating Causal Associations Among Gut Microbiota, Metabolites, and Irritable Bowel Syndrome: A Mendelian Randomization Study

Abstract Background Growing numbers of evidence indicates that changes in the gut microbiota and its metabolites are associated with irritable bowel syndrome (IBS). But their causality has not been clarified. Methods We performed a two-sample Mendelian randomization (MR) study using genome-wide association study (GWAS) summary statistics to estimate the effects of gut microbiota and its metabolites on IBS. FinnGen GWAS (4605 IBS cases and 182423 controls) and UKB GWAS (1121 cases and 360073 controls) were utilized. The discovery set came from the FinnGen consortium while the replication set came from the UK Biobank. Wald ratio (WR), inverse variance weighted (IVW), MR-Egger, and weighted median (WM) were the methods to analyze causality, and MR results are verified by several sensitivity analyses. Results Combining the results of the discovery set and the replication set, we demonstrated a potential causal relationship between Class Actinobacteria (PIVW:9.31E-06, OR:0.632, CI:0.516–0.774), Genus Bifidobacterium (PIVW:3.01E-06, OR:0.667, CI:0.563–0.790), and deoxycholate (PWR: 0.043, OR: 3.412, CI: 1.041–11.180) and IBS. We found that Class Actinobacteria and Genus Bifidobacterium reduced the risk of IBS while deoxycholate increased its risk. In reverse MR analysis, the IVW results revealed no causal relationship between IBS and gut microbiota and its metabolites which were positive results screened in the discovery set. Further analysis of heterogeneity (P > 0.05) and pleiotropy (P > 0.05) confirmed the robustness of MR results. Conclusions We proved a potential causal relationship between the gut microbiota and its metabolites and IBS, providing new biomarkers for gut health and IBS treatment targets, However, further research is needed to determine their exact relationships.