Mendelian randomization and FinnGen analysis of the causal relationship between 473 gut microbiota species and...

To investigate the causal associations between Gut Microbiota (GM) and Chronic Sinusitis (CRS) using Mendelian Randomization (MR).

Genome-Wide Association Study (GWAS) summary statistics for 473 GM taxa were obtained from MiBioGen consortium. CRS data (22,099 cases vs. 371,520 controls) were sourced from the FinnGen R12 cohort. Causal effects were estimated via Inverse Variance-Weighted (IVW), MR-Egger, weighted median, and Bayesian-weighted MR methods. Sensitivity analyses (heterogeneity and horizontal pleiotropy tests) were performed to validate robustness.

IVW analysis identified 20 GM taxa significantly associated with CRS risk (p < 0.05). Of these, 7 taxa (e.g., Francisellales, Roseibacillus, Merdibacter massiliensis) exhibited risk-increasing effects, while 13 taxa (e.g., Firmicutes I, Succinivibrionaceae) showed protective effects. Sensitivity analyses confirmed the absence of significant heterogeneity (Cochran's Q p > 0.05) or pleiotropy (MR-Egger intercept p > 0.05). Bayesian-weighted MR validated 18 causal relationships (posterior probability > 95%), except for RUG420 sp900317985 and UBA7703 (non-significant).

This MR study provides genetic evidence supporting causal roles of specific GM taxa in CRS pathogenesis. These findings highlight the gut-sinus axis as a potential therapeutic target and underscore the utility of large-scale biobanks (e.g., FinnGen) in advancing precision medicine.

Level 5. Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.