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解读微生物群-肠道-眼轴:肠道微生物群对近视因果影响的孟德尔随机化分析

Deciphering the Microbiome-Gut-Eye Axis: A Mendelian Randomization Analysis of the Causal Influence of Gut Microbiota on Myopia.

作者信息

Xu Weicheng, Shi Wei

机构信息

First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

Department of Ophthalmology, Rugao Affiliated Hospital of Nanjing University of Chinese Medicine, Nantong, Jiangsu, China.

出版信息

Comb Chem High Throughput Screen. 2025 Apr 29. doi: 10.2174/0113862073385717250415110224.

DOI:10.2174/0113862073385717250415110224
PMID:40304340
Abstract

BACKGROUND

The intricate relationship between the gut microbiome and myopia is increasingly recognized, underscoring the need to explore its causal dynamics. Despite emerging evidence, the influence of Gut Microbiota (GM) on ocular development remains underexplored.

METHODS

This study utilized Mendelian Randomization (MR) to investigate the causal impact of GM on the development of myopia. Instrumental variables (IVs) were identified from Genome- Wide Association Studies (GWAS), focusing on genetic variants significantly associated with microbiome composition. A comprehensive array of MR techniques was applied to ensure a robust estimation of causal effects and to adjust for potential confounders and pleiotropy.

RESULTS

The Inverse-Variance Weighted (IVW) method was used to identify significant associations between GM and myopia. Increased risk of myopia was linked to the class Betaproteobacteria (OR=1.01, 95% CI 1.004-1.017, P=0.003), the order Burkholderiales (OR=1.009, 95% CI 1.001-1.016, P=0.02), the family Oxalobacteraceae (OR=1.005, 95% CI 1.001-1.01, P=0.023), and several genera including Eubacterium xylanophilum group (OR=1.007, 95% CI 1.001-1.013, P=0.033), and Bifidobacterium (OR=1.005, 95% CI 1-1.01, P=0.038). Protective effects were noted for the order Mollicutes RF9 (OR=0.994, 95% CI 0.99-0.999, P=0.014), the genus Allisonella (OR=0.996, 95% CI 0.993-0.999, P=0.019), the genus Lachnospiraceae UCG001 (OR=0.994, 95% CI 0.989-1, P=0.045), and the family Enterobacteraceae (OR=0.991, 95% CI 0.982-1, P=0.047) and order Enterobacteriales (OR=0.991, 95% CI 0.982-1, P=0.047). Sensitivity analyses further confirmed the robustness of these findings.

CONCLUSIONS

The findings support the "Microbiome-Gut-Eye Axis" as a potential factor in myopia pathogenesis and highlight microbiota-targeted interventions as novel therapeutic strategies for managing myopia. This study lays the groundwork for further research on how modifying GM can influence eye health and offers new perspectives on preventive health strategies.

摘要

背景

肠道微生物群与近视之间复杂的关系日益受到认可,这凸显了探索其因果动态关系的必要性。尽管有新出现的证据,但肠道微生物群(GM)对眼部发育的影响仍未得到充分研究。

方法

本研究利用孟德尔随机化(MR)来研究GM对近视发展的因果影响。从全基因组关联研究(GWAS)中确定工具变量(IVs),重点关注与微生物群组成显著相关的基因变异。应用了一系列全面的MR技术,以确保对因果效应进行稳健估计,并对潜在的混杂因素和多效性进行调整。

结果

采用逆方差加权(IVW)方法来确定GM与近视之间的显著关联。近视风险增加与β-变形菌纲(OR=1.01,95%CI 1.004-1.017,P=0.003)、伯克霍尔德菌目(OR=1.009,95%CI 1.001-1.016,P=0.02)、草酸杆菌科(OR=1.005,95%CI 1.001-1.01,P=0.023)以及几个属有关,包括嗜木真杆菌属群(OR=1.007,95%CI 1.001-1.013,P=0.033)和双歧杆菌属(OR=1.005,95%CI 1-1.01,P=0.038)。对于柔膜菌纲RF9目(OR=0.994,95%CI 0.99-0.999,P=0.014)、Allisonella属(OR=0.996,95%CI 0.993-0.999,P=0.019)、毛螺菌科UCG001属(OR=0.994,95%CI 0.989-1,P=0.045)、肠杆菌科(OR=0.991,95%CI 0.982-1,P=0.047)和肠杆菌目(OR=0.991,95%CI 0.982-1,P=0.047)观察到有保护作用。敏感性分析进一步证实了这些发现的稳健性。

结论

这些发现支持“微生物群-肠道-眼轴”作为近视发病机制中的一个潜在因素,并强调以微生物群为靶点的干预措施作为管理近视的新型治疗策略。本研究为进一步研究改变GM如何影响眼部健康奠定了基础,并为预防性健康策略提供了新的视角。

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