Study on the causal relationship between gut microbiota and giant cell arteritis and its treatment strategies based on mendelian randomization and bioinformatics

Zhouxuan LEI; Zheming XIONG; Jingxin GE; Ling YE; Hui ZHANG; Xiankui SHU; Yanfang YANG; Hezhen WU; Bo LIU

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Study on the causal relationship between gut microbiota and giant cell arteritis and its treatment strategies based on mendelian randomization and bioinformatics

VernacularTitle:基于孟德尔随机化法和生物信息学的肠道菌群与巨细胞动脉炎的因果关系及其治疗策略研究
Author: Zhouxuan LEI ¹ ; Zheming XIONG ¹ ; Jingxin GE ¹ ; Ling YE ¹ ; Hui ZHANG ¹ ; Xiankui SHU ¹ ; Yanfang YANG ¹ ; Hezhen WU ¹ ; Bo LIU ¹
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1. 湖北中医药大学药学院，武汉　430065
Publication Type:Journal Article
Keywords: Giant cell arteritis; Gastrointestinal microbiome; Autoimmune diseases; Genistein
From: Chinese Journal of Rheumatology 2025;29(1):38-47
CountryChina
Language:Chinese
Abstract: Objective:To explore the relationship between gut microbiota and giant cell arteritis (GCA), and to identifyits potential therapeutic strategies.Methods:Gut microbiota data were obtained from the MiBioGen consortium genome-wide association study (GWAS), and GCA data were obtained from the FinnGen consortium public GWAS. Causal associations between gut microbiota and GCA were assessed using two-sample Mendelian randomization (MR) analyses, including inverse-variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods. Heterogeneity and horizontal pleiotropy were evaluated, and false positive results were excluded by using the Benjamini-Hochberg (BH) method of multiple hypothesis testing. All analyses were completed using the TwoSampleMR and MRPRESSO software packages (version 4.3.0) in R language. The analysis of the intestinal flora data, followed by conducting network pharmacology analysis were carried out by Cytoscape 3.9.1 and perform molecular docking verification was performed with AutoDock Vina software.Results:IVW simulations revealed 13 gut microbiota taxa were associated with GCA, of which Lachnospiraceae was significantly negatively associated with GCA risk[nSNP=16, OR(95% CI)=0.32(0.16, 0.63), β=-1.15, Se=0.35, P=0.001, FDR<0.05], and there was no heterogeneity (Cochran′s Q test, Q=13.42, P=0.490) as well as horizontal pleiotropy ( P=0.370). Further literature search and computer simulation docking analysis showed that genistein binds to MMP2 with a binding energy of -43.1 kJ/mol. Conclusion:Lachnospiraceae in the gut microbiota was is negatively associated with GCA, and genistein may be able to regulate the abundance of Lachnospiraceae through the MMP2 target to treat GCA, providing a new therapeutic approach for giant cell arteritis.