Luo Maomei, Xing Zhen, Gou Yanhao, Yang Xianlin, Zhang Xinran, Yu Wei, Lv Hongbin
Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Transl Vis Sci Technol. 2025 May 1;14(5):15. doi: 10.1167/tvst.14.5.15.
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.
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.
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.
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.
This study provides evidence that modulating the intestinal flora and its metabolic pathways is effective in treating uveitis.
一些实验报告提出肠道微生物群（GM）与葡萄膜炎之间存在相互作用。然而，GM及其代谢途径与葡萄膜炎之间的确切关联仍不清楚。本研究旨在探讨GM及其代谢途径与葡萄膜炎之间的双向因果关系。
GM及其代谢途径和葡萄膜炎的汇总数据分别来自荷兰微生物组计划和全基因组关联研究（GWAS）目录。然后，我们进行了孟德尔随机化（MR）分析，以探讨GM及其代谢途径与葡萄膜炎是否存在相应的因果关系。为了确认研究结果的可信度，我们使用MR-Egger、MR-PRESSO全局检验和Cochran Q检验来检测多效性和异质性。
根据逆方差加权法，粪便拟杆菌（优势比[OR]=0.598，95%置信区间[CI]=0.390–0.919，P=0.019）以及硫酸盐同化和半胱氨酸生物合成的超级途径（OR=0.179，95%CI=0.038–0.843，P=0.029）对葡萄膜炎有有益影响。相反，萨特氏菌属（OR=3.493，95%CI=1.121–10.879，P=0.030）；狄氏副拟杆菌（OR=5.932，95%CI=1.321–26.635，P=0.020）、普拉梭菌（OR=4.838，95%CI=1.067–21.936，P=0.040）和粪栖拟杆菌（OR=3.818，95%CI=1.010–14.437，P=0.048）；以及1,2-丙二醇降解（OR=2.084，95%CI=1.098–3.954，P=0.024）、半乳糖降解I（Leloir途径；OR=3.815，95%CI=1.108–13.135，P=0.033）、三羧酸循环VI（专性自养生物；OR=2.955，95%CI=1.015–8.606，P=0.046）和尿苷一磷酸生物合成（OR=4.979，95%CI=1.000–24.782，P=0.049）途径对葡萄膜炎有不利影响。未发现多效性或异质性。留一法分析表明上述研究结果具有可靠性。
我们的分析通过遗传预测揭示了某些GM物种及其代谢途径与葡萄膜炎之间的因果关系，这可能为葡萄膜炎的病因学和治疗提供新的视角。
本研究提供了证据，表明调节肠道菌群及其代谢途径对治疗葡萄膜炎有效。
