Aier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China; The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Aier Glaucoma Institute, Hunan Engineering Research Center for Glaucoma with Artificial Intelligence in Diagnosis and Application of New Materials, Changsha Aier Eye Hospital, Changsha, Hunan, China; The Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Exp Eye Res. 2024 Mar;240:109788. doi: 10.1016/j.exer.2024.109788. Epub 2024 Jan 11.
Primary open-angle glaucoma (POAG) is a widespread condition responsible for irreversible blindness, and its prevalence is expected to increase substantially in the coming decades. Despite its significance, the exact cause of POAG remains elusive, necessitating a comprehensive exploration of its pathogenesis. Emerging research suggests a potential link between alterations in gut microbiota composition and POAG. However, establishing causality in these associations remains a challenge. In this study, we employed Mendelian randomization (MR) analysis to investigate the potential causal relationships between gut microbiota (GM) and POAG. Significant bacteria taxa were further analyzed with POAG endophenotypes. We utilized data from genome-wide association studies (GWAS) for GM and POAG, as well as for glaucoma endophenotypes, including intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, vertical cup-to-disc ratio (VCDR), and central corneal thickness (CCT). Univariable, multivariable MR and mediation effect analysis were conducted. Our analysis revealed that certain taxa, including phylum Euryarchaeota, genus Odoribacter, Rumnicoccaceae UCG009, Ruminiclostridium9, unknown genus id.2071, and Eubacterium rectale group, were associated with an increased risk of POAG. On the other hand, family Victivallaceae, Lacchnospiraceae, genus Lachnoclostridium, Oscillospira, Ruminococcaceae UCG011, Alloprevotella, and Faecalibacterium were found to be associated with a decreased risk of POAG. Furthermore, some of these taxa were found to be connected to glaucoma endophenotypes. Through further multivariable MR analysis, it was determined that IOP, VCDR, and CCT might played mediating roles between GM and POAG. In conclusion, this study utilizes MR analysis to elucidate potential causal associations between GM and POAG, providing insights into specific GM taxa that influence POAG risk and related endophenotypes. These findings emphasize the potential role of the gut microbiota in the pathogenesis of POAG and pave the way for future research and therapeutic interventions.
原发性开角型青光眼（POAG）是一种广泛存在的疾病，可导致不可逆性失明，预计在未来几十年其患病率将大幅上升。尽管其意义重大，但 POAG 的确切病因仍不清楚，需要全面探索其发病机制。新的研究表明，肠道微生物群落组成的改变与 POAG 之间可能存在关联。然而，在这些关联中确定因果关系仍然是一个挑战。在这项研究中，我们采用孟德尔随机化（MR）分析来研究肠道微生物群（GM）与 POAG 之间潜在的因果关系。进一步对与 POAG 表型相关的显著细菌分类群进行了分析。我们利用 GM 和 POAG 的全基因组关联研究（GWAS）数据，以及青光眼表型的 GWAS 数据，包括眼压（IOP）、视网膜神经纤维层（RNFL）厚度、垂直杯盘比（VCDR）和中央角膜厚度（CCT）。进行了单变量、多变量 MR 和中介效应分析。我们的分析表明，某些分类群，包括门古菌、属 Odoribacter、瘤胃球菌科 UCG009、瘤胃真杆菌属 Ruminiclostridium9、未知属 id.2071 和直肠真杆菌属，与 POAG 风险增加有关。另一方面，科 Victivallaceae、毛螺科、属 Lachnoclostridium、颤螺菌属、瘤胃球菌科 UCG011、Alloprevotella 和粪杆菌与 POAG 风险降低有关。此外，其中一些分类群与青光眼表型有关。通过进一步的多变量 MR 分析，确定 IOP、VCDR 和 CCT 可能在 GM 和 POAG 之间发挥中介作用。总之，本研究利用 MR 分析阐明了 GM 与 POAG 之间潜在的因果关联，为影响 POAG 风险和相关表型的特定 GM 分类群提供了新的见解。这些发现强调了肠道微生物群在 POAG 发病机制中的潜在作用，并为未来的研究和治疗干预铺平了道路。
