临床与病理杂志2023，Vol.43Issue(9)：1631-1641,11.DOI:10.11817/j.issn.2095-6959.2023.230041
肠道菌群代谢物参与高尿酸血症的病理机制
Pathological mechanisms of gut microbiota metabolites in hyperuricemia
摘要
Abstract
Objective:To investigate the role of metabolites of gut microbiota metabolites in the pathogenesis of hyperuricemia. Methods:Gut microbiota metabolites were collected from the Target Genes of Gut Microbes and Microbial Metabolites(gutMGene)database,and their targets were obtained.The disease targets of hyperuricemia were obtained from the DisGeNET,Drugbank,Genecard,and OMIM databases.The intersection of gut microbiota metabolites targets and disease targets was obtained to identify common targets.These common targets were then intersected with the 223 known human gut microbiota metabolites targets in the gutMGene database to obtain the targets of gut microbiota metabolites involved in hyperuricemia.A target protein-protein interaction(PPI)network was constructed using STRING,and core proteins were obtained using cytoscape 3.8.0 software,gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed using the DAVID database.A gut microbiata-metabolite-target-pathway-disease(MMTPD)network was constructed and molecular docking using AutoDockVene was performed to validate the interaction between active metabolites and core targets. Results:A total of 208 gut microbiota metabolites and their corresponding 668 targets,827 disease targets,and the intersection of the two yielded 99 targets were obtained.By intersecting with the 223 known human gut metabolite targets in the gutMGene database,20 key targets were identified.The PPI network showed that cytochrome P450 family 3 subfamily A member 4(CYP3A4),peroxisome proliferator-activated receptor gamma(PPARG),and interleukin 6(IL-6)were core targets.GO function and KEGG pathway enrichment analysis revealed that gut microbiota metabolites were mainly involved in biological processes such as gene regulation,inflammatory response,and cellular response to lipopolysaccharide,through IL-17 signaling pathway,Toll-like receptor signaling pathway,etc.The MMTPD network showed a close relationship between short-chain fatty acid-like metabolites and hyperuricemia,with butyric acid playing a prominent role.Molecular docking results showed that acetic acid,propionic acid,and butyric acid bound well with CYP3A4,PPARG,and IL-6,with butyric acid showing the strongest binding affinity to IL-6. Conclusion:Short-chain fatty acids may be an important class of gut microbiota metabolites affecting hyperuricemia,and their intervention pathway may be achieved through butyric acid modulation target of the IL-6 and Toll-like receptor signaling pathways.关键词
高尿酸血症/肠道菌群/肠道菌群代谢物/短链脂肪酸/网络生物学Key words
hyperuricemia/gut microbiota/gut microbiota metabolites/short-chain fatty acids/network biology引用本文复制引用
杨莹,韩宇,黄锦坚,王雨,林志健,张冰..肠道菌群代谢物参与高尿酸血症的病理机制[J].临床与病理杂志,2023,43(9):1631-1641,11.基金项目
国家自然科学基金(U20A20406) （U20A20406）
中央高校基本科研业务费专项资金(2023-JYB-XJSJJ-007) （2023-JYB-XJSJJ-007）
北京市自然科学基金(7212178).This work was supported by the National Natural Science Foundation(U20A20406),the Fundamental Research Funds for the Central Universities(2023-JYB-XJSJJ-007),and the Beijing Municipal Natural Science Foundation(7212178),China. （7212178）
