The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine.
The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine.
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DOI：
10.1007/s13167-023-00336-2
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发表时间：
2023-09
期刊：
影响因子：
6.5
通讯作者：
Xia, Xiaobo
中科院分区：
文献类型：
--
作者：
Chen, Si;Wang, Nan;Xiong, Siqi;Xia, Xiaobo
关键词：
青光眼是世界范围内不可逆性失明的主要原因。出现的证据表明，青光眼被认为是一种免疫系统相关疾病。肠道是人体最大的免疫器官，肠道微生物群在维持免疫稳态中起着不可逆的作用。但是，转基因如何影响青光眼仍然没有揭示。本研究旨在研究介导GM和青光眼的关键分子/途径，为未来的预测，预防和个性化医学提供新的生物标志物。从公共数据库下载原发性开角型青光眼（POAG）患者（GSE 138125）的数据集和GM/GM代谢物靶基因的数据集。对于GSE 138125，鉴定了健康和POAG样品之间的差异表达基因（DEG）。并利用在线文氏图工具获得了与GM相关的POAG的DEG。然后采用相关性分析、途径富集分析和蛋白质相互作用网络分析等方法对转基因相关DEG进行分析。使用人小梁网细胞进行验证，并在体外青光眼模型中通过定量实时聚合酶链反应（RT-qPCR）验证hub基因的mRNA水平。从上述两个数据集中共鉴定出16个GM相关DEG（9个上调基因和7个下调基因）。途径富集分析表明，这些基因主要富集在免疫调节尤其是巨噬细胞相关途径中。通过PPI网络分析和关键模块的构建，筛选出6个hub基因。RT-qPCR证实hub基因在体外青光眼模型中的表达与mRNA芯片的生物信息学分析结果一致。这项生物信息学研究阐明了NFKB 1，IL 18，KITLG，TLR 9，FKBP 2和HDAC 4作为POAG和GM调控的枢纽基因。巨噬细胞调节的免疫反应在POAG中起着重要作用，并可能成为未来预测、预防和个性化诊断和治疗的潜在靶点。在线版本包含补充材料，可通过10.1007/s13167-023-00336-2获得。
Glaucoma is the leading cause of irreversible blindness worldwide. Emerged evidence has shown that glaucoma is considered an immune system related disorder. The gut is the largest immune organ in the human body and the gut microbiota (GM) plays an irreversible role in maintaining immune homeostasis. But, how the GM influences glaucoma remains unrevealed. This study aimed at investigating the key molecules/pathways mediating the GM and the glaucoma to provide new biomarkers for future predictive, preventive, and personalized medicine. Datasets from the primary open-angle glaucoma (POAG) patients (GSE138125) and datasets for target genes of GM/GM metabolites were downloaded from a 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 the mRNA level of hub genes was verified by quantitative real-time polymerase chain reaction (RT-qPCR) in the in vitro glaucoma model. A total of 16 GM-related DEGs in POAG were identified from the above 2 datasets (9 upregulated genes and 7 downregulated 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 the mRNA chip. This bioinformatic study elucidates NFKB1, IL18, KITLG, TLR9, FKBP2, and HDAC4 as hub genes for POAG and GM regulation. Immune response modulated by macrophages plays an important role in POAG and may be potential targets for future predictive, preventive, and personalized diagnosis and treatment. The online version contains supplementary material available at 10.1007/s13167-023-00336-2.
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作者：
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DOI：
10.1007/s13167-021-00260-3
发表时间：
2021-12
期刊：
The EPMA journal
影响因子：
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通讯作者：
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