Xie Xiaodong, Ren Weina, Zhou Weiping, Zhang Xixi, Deng Xiaoyu, Wang Xinyi, Wu Yufei, Lu Qinkang
The Affiliated Peoples Hospital of Ningbo University, Ningbo, Zhejiang, China.
School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Medicine (Baltimore). 2024 Dec 13;103(50):e40922. doi: 10.1097/MD.0000000000040922.
The gut microbiota (GM) may be associated with uveitis. However, the causal relationship between the GM and uveitis and whether blood metabolites act as mediators of the GM remain unclear. We extracted the GM, blood metabolites, and uveitis data from genome-wide association study (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships among GM, blood metabolites, and uveitis. The primary statistical method used was the inverse variance weighted (IVW) method. In addition, we used 2-sample MR, bidirectional MR, 2-step method and multiple MR to explore whether blood metabolites were mediators of the association between the GM and uveitis. After removing confounding factors, the abundances of the order Bacillales and the genus Holdemanella are risk factors for uveitis, and the abundances of Peptococcus and Ruminococcaceae UCG010 are protective factors. The inverse analysis revealed that uveitis affected 6 GM taxa - 4 positively and 2 negatively. In addition, N-methyl proline and 2-hydroxy sebacate were identified as risk factors for uveitis, and N-formy1 phenylalanine, 1-ribosyl-imidazole acetate, 1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) and alpha-ketoglutarate/pyruvate were identified as protective factors for uveitis. Finally, there was a causal association between 3 GM taxa and 6 blood metabolites, with 6 positive and 2 negative effects. N-methylproline possessed the greatest mediated effect (9.41%) between Ruminococcaceae UCG010 and uveitis. These results provide new insights into the pathogenesis of uveitis and offer a new approach to uveitis prevention and treatment from GM and blood metabolites perspective.
肠道微生物群（GM）可能与葡萄膜炎有关。然而，GM与葡萄膜炎之间的因果关系以及血液代谢物是否作为GM的介质仍不清楚。我们从全基因组关联研究（GWAS）汇总数据中提取了GM、血液代谢物和葡萄膜炎数据。我们使用孟德尔随机化（MR）来研究GM、血液代谢物和葡萄膜炎之间的因果关系。使用的主要统计方法是逆方差加权（IVW）法。此外，我们使用两样本MR、双向MR、两步法和多重MR来探讨血液代谢物是否是GM与葡萄膜炎之间关联的介质。去除混杂因素后，芽孢杆菌目和霍尔德曼菌属的丰度是葡萄膜炎的危险因素，消化球菌属和瘤胃球菌科UCG010的丰度是保护因素。反向分析显示，葡萄膜炎影响6个GM分类群，4个为正向影响，2个为负向影响。此外，N-甲基脯氨酸和2-羟基癸二酸被确定为葡萄膜炎的危险因素，N-甲酰基苯丙氨酸、1-核糖基-咪唑乙酸、1-棕榈酰-2-花生四烯酰-GPE（16:0/20:4）和α-酮戊二酸/丙酮酸被确定为葡萄膜炎的保护因素。最后，3个GM分类群与6种血液代谢物之间存在因果关联，其中6个为正向影响，2个为负向影响。N-甲基脯氨酸在瘤胃球菌科UCG010与葡萄膜炎之间具有最大的介导作用（9.41%）。这些结果为葡萄膜炎的发病机制提供了新的见解，并从GM和血液代谢物的角度为葡萄膜炎的预防和治疗提供了新的方法。
