The correlation between primary open-angle glaucoma(POAG) and gut microbiota: a potential towards predictive, preventive, and personalized medicine

Abstract

Abstract Background Glaucoma is the leading cause of irreversible blindness worldwide. Emerged evidence has shown that glaucoma is considered an immune disorder. Gut is the largest immune organ in human body and gut microbiota (GM) plays irreversible role of maintaining immune homeostasis. But how does GM influences glaucoma remain unrevealed. This study aimed at investigating key molecules/pathways mediating GM and glaucoma and provide new biomarkers for future predictive, preventive, and personalized medicine. Methods Datasets from primary open-angle glaucoma (POAG) patients (GSE138125) and datasets for target genes of GM/GM metabolites were downloaded from public database. For GSE138125, the differentially expressed genes (DEGs) between healthy and POAG samples were identified. And the online Venn diagram tool was used to obtain the DEGs from POAG related to GM. After which GM-related DEGs were analyzed by correlation analysis, pathway enrichment analysis and protein-protein interaction (PPI) network analysis. Human trabecular meshwork cells were used for validation, and mRNA level of hub genes was verified by quantitative real-time polymerase chain reaction (RT-qPCR) in the in vitro glaucoma model. Results A total of 16 GM-related DEGs in POAG were identified from the above 2 datasets (9 up-regulated genes and 7 down-regulated genes). Pathway enrichment analysis indicated that these genes are mostly enriched in immune regulation especially macrophages related pathways. Then 6 hub genes were identified by PPI network analysis and construction of key modules. Finally, RT-qPCR confirmed that the expression of the hub genes in the in vitro glaucoma model was consistent with the results of bioinformatics analysis of mRNA chip. Conclusion This bioinformatic study elucidates NFKB1, IL18, KITLG, TLR9, FKBP2, and HDAC4 as hub genes for POAG and GM regulation. Immune response modulated by macrophages play an important role in POAG and may be potential targets for future predictive, preventive, and personalized diagnosis and treatment.