Associations Between the Gut Microbiota and Its Related Metabolic Pathways and Uveitis: A Bidirectional Two-Sample Mendelian Randomization Study.

Purpose: Some experimental reports have proposed an interaction between gut microbiota (GM) and uveitis. However, the exact association between GM and its metabolic pathways and uveitis remains unknown. This study was conducted to explore the bidirectional causal relationship between GM and its metabolic pathways and uveitis.

Methods: Summary data of the GM and its metabolic pathways and uveitis were leveraged from the Dutch Microbiome Project and the Genome-Wide Association Studies (GWAS) Catalog, respectively. We then conducted Mendelian randomization (MR) analysis to explore whether the GM and its metabolic pathways have a corresponding causal relationship with uveitis. To confirm the credibility of the findings, we utilized MR Egger, the MR-PRESSO global test, and the Cochran Q test to detect pleiotropy and heterogeneity.

Results: According to the inverse variance weighting method, the species Bacteroides faecis (odds ratio [OR] = 0.598, 95% confidence interval [CI] = 0.390–0.919, P = 0.019) and the superpathway of sulfate assimilation and cysteine biosynthesis (OR = 0.179, 95% CI = 0.038–0.843, P = 0.029) had beneficial effects on uveitis. In contrast, the genus Sutterellaceae (OR = 3.493, 95% CI = 1.121–10.879, P = 0.030); the species Parabacteroides distasonis (OR = 5.932, 95% CI = 1.321–26.635, P = 0.020), Faecalibacterium prausnitzii (OR = 4.838, 95% CI = 1.067–21.936, P = 0.040), and Bacteroides caccae (OR = 3.818, 95% CI = 1.010–14.437, P = 0.048); and the L1,2–propanediol degradation (OR = 2.084, 95% CI = 1.098–3.954, P = 0.024), galactose degradation I (Leloir pathway; OR = 3.815, 95% CI = 1.108–13.135, P = 0.033), TCA cycle VI (obligate autotrophs; OR = 2.955, 95% CI = 1.015–8.606, P = 0.046) and UMP biosynthesis (OR = 4.979, 95% CI = 1.000–24.782, P = 0.049) pathways had adverse effects on uveitis. No pleiotropy or heterogeneity was found. Leave-one-out analysis showed the reliability of the above findings.

Conclusions: Our analysis revealed a causality between certain GM species and metabolic pathways and uveitis via genetic prediction, which may provide new perspectives into the etiology and therapies of uveitis.

Translational relevance: This study provides evidence that modulating the intestinal flora and its metabolic pathways is effective in treating uveitis.