Causal Links between Gut Microbiota, Blood Metabolites, Immune Cells, Inflammatory Proteins, and Myopia: A Mendelian Randomization Study

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2024-12-17 DOI:10.1016/j.xops.2024.100684

Huibin Lv MD , Zhenyu Wang MD , Chen Huang MD , Xiaotong Yu MS , Xuemin Li MD , Xudong Song MD

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Abstract

Purpose

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.

Design

Mendelian randomization study.

Subjects

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.

Methods

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.

Main Outcome Measures

Causal relationships between gut microbiota, blood metabolites, immune cell traits, circulating inflammatory proteins, and myopia.

Results

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.

Conclusions

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.

Financial Disclosure(s)

The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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肠道微生物群、血液代谢物、免疫细胞、炎症蛋白和近视之间的因果关系：一项孟德尔随机研究

目的通过孟德尔随机化（Mendelian randomization， MR）分析，探讨肠道菌群、血液代谢产物、免疫细胞特征、循环炎症蛋白与近视的因果关系。设计孟德尔随机化研究。研究对象：来自公共GWAS数据库的412个肠道微生物群、1400个血液代谢物/代谢物比率、731个免疫细胞特征和91个循环炎症蛋白的全基因组关联研究（GWAS）数据。来自公共GWAS数据库和FinnGen联盟的近视全基因组关联研究数据。方法采用4种方法进行双样本MR分析和meta分析，以反方差加权为主要方法，探讨潜在的因果关系。进行代谢途径分析，探索代谢途径。采用Cochran q检验、MR-Egger截距检验和MR-PRESSO进行敏感性分析。还进行了中介和反向MR分析，以确定潜在的中介关系和近视的调节效应。肠道微生物群、血液代谢物、免疫细胞特征、循环炎症蛋白和近视之间的因果关系。结果我们确定了34和22种肠道菌群/细菌途径、131和98种血液代谢物/代谢物比率、60和37种免疫细胞特征以及5和2种循环炎症蛋白（分别为ukb-b-6353和R10_H7_MYOPIA）与近视的因果关系。在两种结果中发现了1种肠道细菌途径、10种血液代谢物/代谢物比率和2种免疫细胞特征的重叠因果关系；然而，经过荟萃分析，这些重叠都没有达到显著性。小分子途径数据库和京都基因与基因组百科数据库丰富了14条重要途径。黄素腺嘌呤二核苷酸参与了8条通路。此外，乙酰辅酶a发酵丁酸lI介导了糖醛酸苷对近视的因果效应，介导比例分别为19.03% （ukb-b-6353）和19.48% （R10_H7_MYOPIA）。反向磁共振分析发现近视（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作用。结论肠道菌群、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。肠道菌群通路可能介导血液代谢物对近视的因果作用。这可能为研究近视眼的生物学机制提供新的视角，并可能导致探索早期治疗策略。财务披露作者在本文中讨论的任何材料中没有专有或商业利益。

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