Zhang Yinglei, Zhou Xujiao, Lu Yi
Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai, China.
Eye Institute, Eye and ENT Hospital of Fudan University, Shanghai, China.
Front Cell Infect Microbiol. 2022 Aug 12;12:968992. doi: 10.3389/fcimb.2022.968992. eCollection 2022.
Glaucoma is a multifactorial, neurodegenerative disorder characterized by the loss of retinal ganglion cells (RGCs). Crosstalk between the gut microbiota and host is involved in the progression of many neurodegenerative diseases, although little is known about its role in glaucoma. To investigated the alterations of the gut microbiota and derived metabolites in glaucomatous rats, and the interaction with RGCs, we performed 16S rRNA (V1-V9) sequencing and untargeted metabolomic analyses. The microbial composition differed significantly between the two groups, and the diversity of cecal bacteria was dramatically reduced in glaucomatous rats. The Firmicutes/Bacteroidetes (F/B) ratio, Verrucomicrobia phylum, and some bacterial genera (Romboutsia, Akkermansia, and Bacteroides) were dramatically increased in the glaucomatous rat model compared with the control, which showed negative correlation with RGCs. Untargeted metabolomic analysis identified 284 differentially expressed metabolites, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed considerable enrichment mainly in bile secretion pathways. The relationships among the metabolites enriched in the bile secretion pathway, differentially expressed cecal microbiota, and RGCs were investigated, and glutathione (GSH) was found to be negatively correlated with Bacteroides and F/B and positively correlated with RGCs. Reduced GSH level in the blood of glaucoma rats is further established, and was negatively correlated with Romboutsia and the F/B ratio and positively correlated with RGCs. This finding suggests the potential role of the gut microbiota and derived metabolites in glaucoma, and GSH, a major antioxidant metabolite, was related to their effects, indicating the potential for the development of gut microbiota-targeted interventions for glaucoma.
青光眼是一种多因素神经退行性疾病，其特征是视网膜神经节细胞（RGCs）丢失。肠道微生物群与宿主之间的相互作用参与了许多神经退行性疾病的进展，尽管其在青光眼中的作用尚不清楚。为了研究青光眼大鼠肠道微生物群及其衍生代谢产物的变化，以及它们与RGCs的相互作用，我们进行了16S rRNA（V1-V9）测序和非靶向代谢组学分析。两组之间的微生物组成存在显著差异，青光眼大鼠盲肠细菌的多样性显著降低。与对照组相比，青光眼大鼠模型中的厚壁菌门/拟杆菌门（F/B）比值、疣微菌门和一些细菌属（罗姆布茨菌属、阿克曼氏菌属和拟杆菌属）显著增加，且与RGCs呈负相关。非靶向代谢组学分析鉴定出284种差异表达的代谢产物，京都基因与基因组百科全书通路富集分析显示主要在胆汁分泌通路中有大量富集。研究了胆汁分泌通路中富集的代谢产物、差异表达的盲肠微生物群和RGCs之间的关系，发现谷胱甘肽（GSH）与拟杆菌属和F/B呈负相关，与RGCs呈正相关。进一步证实了青光眼大鼠血液中GSH水平降低，且与罗姆布茨菌属和F/B比值呈负相关，与RGCs呈正相关。这一发现表明肠道微生物群及其衍生代谢产物在青光眼中的潜在作用，而主要抗氧化代谢产物GSH与其作用相关，这表明针对肠道微生物群的青光眼干预措施具有开发潜力。
