Lv Huibin, Wang Zhenyu, Huang Chen, Yu Xiaotong, Li Xuemin, Song Xudong
Department of Ophthalmology, Peking University Third Hospital, Beijing, China.
Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Ophthalmol Sci. 2024 Dec 17;5(4):100684. doi: 10.1016/j.xops.2024.100684. eCollection 2025 Jul-Aug.
This study aimed to investigate causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia through Mendelian randomization (MR) analysis.
Mendelian randomization study.
Genome-wide association study (GWAS) data of 412 gut microbiota, 1400 blood metabolites/metabolite ratios, 731 immune cell traits, and 91 circulating inflammatory proteins from the public GWAS database. Genome-wide association study data of myopia from the public GWAS database and FinnGen consortium.
Two-sample MR analysis and meta-analysis were employed using 4 methods, with inverse-variance weighted as the primary approach, to investigate potential causal links. Metabolic pathway analysis was conducted to explore metabolic pathways. The Cochran Q-test, MR-Egger intercept test, and MR-PRESSO were used for sensitivity analyses. Mediation and reverse MR analyses were also carried out to identify potential mediation relationships and modification effects of myopia.
Causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia.
We identified causal effects of 34 and 22 gut microbiota/bacterial pathways, 131 and 98 blood metabolites/metabolite ratios, 60 and 37 immune cell traits, and 5 and 2 circulating inflammatory proteins on myopia (ukb-b-6353 and R10_H7_MYOPIA, respectively). Overlapping causal relationships were found for 1 gut bacterial pathway, 10 blood metabolites/metabolite ratios, and 2 immune cell traits across both outcomes; however, none of these overlaps reached significance after meta-analysis. The Small Molecule Pathway Database and Kyoto Encyclopedia of Genes and Genomes database enriched 14 significant pathways. Flavin adenine dinucleotide was involved in 8 pathways in both databases. Furthermore, the causal effect of glycochenodeoxycholate glucuronide on myopia was mediated by acetyl-CoA fermentation to butanoate lI, with mediation proportion of 19.03% (ukb-b-6353) and 19.48% (R10_H7_MYOPIA). Reverse MR analysis identified modification effects of myopia (ukb-b-6353) on gut microbiota, blood metabolites, and circulating inflammatory proteins.
These findings demonstrated significant causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia. Gut microbiota pathway may mediate the causal effects of blood metabolite on myopia. This may provide researchers with a new perspective in exploring the biological mechanisms of myopia and may lead to the exploration of earlier treatment strategies.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
本研究旨在通过孟德尔随机化（MR）分析，探讨肠道微生物群、血液代谢物、免疫细胞特征、循环炎症蛋白与近视之间的因果关系。
孟德尔随机化研究。
来自公共全基因组关联研究（GWAS）数据库的412种肠道微生物群、1400种血液代谢物/代谢物比值、731种免疫细胞特征和91种循环炎症蛋白的GWAS数据。来自公共GWAS数据库和芬兰基因组联盟的近视GWAS数据。
采用两种样本的MR分析和荟萃分析，使用4种方法，以逆方差加权法为主要方法，研究潜在的因果联系。进行代谢途径分析以探索代谢途径。使用 Cochr an Q检验、MR-Egger截距检验和MR-PRESSO进行敏感性分析。还进行了中介分析和反向MR分析，以确定近视的潜在中介关系和修饰效应。
肠道微生物群、血液代谢物、免疫细胞特征、循环炎症蛋白与近视之间的因果关系。
我们确定了34种和22种肠道微生物群/细菌途径、131种和98种血液代谢物/代谢物比值、60种和37种免疫细胞特征以及5种和2种循环炎症蛋白对近视的因果效应（分别为ukb-b-6353和R10_H7_MYOPIA）。在两个结果中，发现1种肠道细菌途径、10种血液代谢物/代谢物比值和2种免疫细胞特征存在重叠的因果关系；然而，在荟萃分析后，这些重叠均未达到显著水平。小分子途径数据库和京都基因与基因组百科全书数据库富集了14条显著途径。黄素腺嘌呤二核苷酸在两个数据库的8条途径中均有涉及。此外，甘氨鹅去氧胆酸葡萄糖醛酸对近视的因果效应由乙酰辅酶A发酵生成丁酸II介导，中介比例分别为19.03%（ukb-b-6353）和19.48%（R10_H7_MYOPIA）。反向MR分析确定了近视（ukb-b-6353）对肠道微生物群、血液代谢物和循环炎症蛋白的修饰效应。
这些发现表明肠道微生物群、血液代谢物、免疫细胞特征、循环炎症蛋白与近视之间存在显著的因果关系。肠道微生物群途径可能介导血液代谢物对近视的因果效应。这可能为研究人员探索近视的生物学机制提供新的视角，并可能促使探索更早的治疗策略。
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