Dysbiosis of gut microbiome contributes to glaucoma pathogenesis

作     者：Chen, Shida Wang, Yayi Liu, Yaoming Li, Fei Chen, Yang Fang, Xiuli Wen, Tao Xu, Shuyi Kermany, Daniel Deng, Shufang Li, Gen Zhang, Kang Zhang, Xiulan 

作者机构：State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat-sen University Guangzhou China Department of Ophthalmology West China Hospital Sichuan University Chengdu China Zhuhai International Eye Center Zhuhai People's Hospital and the First Affiliated Hospital of Macau University of Science and Technology Zhuhai China MD/PhD Program School of Medicine Texas A&M University Bryan TX United States Novogene Bioinformatics Institute Beijing China Guangzhou Women and Children's Medical Center Guangzhou China Center for Biomedicine and Innovations Faculty of Medicine Macau University of Science and Technology Macao 

出 版 物：《MedComm - Future Medicine》 (MedComm. Futur. Med.)

年 卷 期：2022年第1卷第2期

基　　金：Fundamental Research Funds of the State Key Laboratory of Ophthalmology Medical Scientist Training Program National Natural Science Foundation of China, NSFC, (81670847, 82070955) National Natural Science Foundation of China, NSFC Guangzhou Municipal Science and Technology Program key projects, (202102010209) Guangzhou Municipal Science and Technology Program key projects Fundo para o Desenvolvimento das Ciências e da Tecnologia, FDCT, (0007/2020/AFJ) Fundo para o Desenvolvimento das Ciências e da Tecnologia, FDCT Basic and Applied Basic Research Foundation of Guangdong Province, (2020A1515011282) Basic and Applied Basic Research Foundation of Guangdong Province 

主　　题：glaucoma microbiome microglia microRNA retinal ganglion cells 

摘      要：Microbiome dysfunction is considered to contribute to the pathogenesis of many neurodegenerative diseases. However, the relationship between the gut microbiome and glaucoma, a neurodegenerative disorder remains largely unknown. Here, we identified that the gut microbiome of glaucoma patients were rich in Dysgonamonadaceae, along with a lower level of Barnesiellaceae by metagenomic sequencing. This microbiome pattern is shown to increased the production of short chain fatty acids (SCFAs) in the fecal and blood samples. Reducing these glaucoma-specific gut microbiome bacteria significantly reduced retinal ganglion cell (RGC) loss by alleviating the activation of retinal microglia cells and overproduction of inflammatory cytokines in acute glaucoma mouse model, whereas SCFAs treatment aggravated microglia activation. Mechanistically, reducing the glaucoma-specific gut microbiome bacteria decreased the retinal microRNA profile including MiR-122-5p, which led to neuroprotection through inhibition of retinal inflammation. We validated our results by showing that fecal microbiome transplantation from glaucoma patients significantly exacerbated retinal microglia activation and increased retinal inflammation. Our findings indicate that the change of gut microbiome is associated with glaucoma, by activation of retinal microglia and changing expression of retinal microRNAs, leading to retinal inflammation reaction and RGC loss. The gut microbiome may be a new target for the neuroprotection in glaucoma. © 2022 The Authors. MedComm – Future Medicine published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).