Causal effects of gut microbiota on functional gastrointestinal disorders: a bidirectional Mendelian randomization study

Abstract

Emerging evidence suggests that gut microbiota is associated with functional gastrointestinal disorders (FGIDs). However, findings regarding microbial alterations in FGIDs have been inconsistent across observational studies, and the direction and causality of these associations remain unclear. We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate potential causal associations between gut microbiota and two common FGIDs, irritable bowel syndrome (IBS) and functional dyspepsia (FD). Genome-wide association study (GWAS) summary statistics of gut microbiota, IBS, and FD were obtained from public databases and applied to our MR analysis. The inverse-variance-weighted method was used as the primary analysis, with weighted median and complementary sensitivity analyses used to assess the consistency and robustness of the findings. Higher genetically predicted abundances of order Bifidobacteriales (OR: 0.741, 95% CI: 0.570 to 0.963, P = 0.025) and genus Eubacterium ventriosum group (OR: 0.684, 95% CI: 0.524 to 0.893, P = 0.005) were associated with a lower risk of IBS. Genus Lachnospiraceae NK4A136 group (OR: 1.368, 95% CI: 1.086 to 1.722, P = 0.008) correlated to a high risk of FD while family Desulfovibrionaceae and order Desulfovibrionales (OR: 0.649, 95% CI: 0.471 to 0.893, P = 0.008) were protective for FD. In the reverse MR analysis, genetically predicted IBS risk was associated with lower abundances of Turicibacter and Slackia, whereas no robust reverse associations were observed for FD. These findings identify several microbial taxa as candidates for further mechanistic and clinical validation rather than established risk factors or therapeutic targets. Further experimental research to investigate the underlying mechanisms is warranted.