Exploring the causal associations of the gut microbiota and plasma metabolites with ovarian cancer: an approach of mendelian randomization analysis combined with network pharmacology and molecular docking

作者：Junfeng Guo, Chen Wang, He Li, Chenhuan Ding · 发表于：Journal of Ovarian Research · 年份：2025 · DOI：10.1186/s13048-025-01610-9 · 被引用次数：8 · 研究领域：Gut microbiota and health、Ferroptosis and cancer prognosis、Clostridium difficile and Clostridium perfringens research

BACKGROUND: While increasing evidence suggests that alterations in the gut microbiota and metabolites are associated with ovarian cancer (OC) risk, whether these associations imply causation remains to be identified. METHODS: We conducted a two-sample Mendelian randomization (MR) study utilizing a large-scale genome-wide association study (GWAS) to explore the causal effects of the gut microbiota of 196/220 individuals and 1,400 plasma metabolites on OC and epithelial ovarian cancer (EOC) subtypes. Data on the gut microbiota were obtained from the MiBioGen consortium of 18,340 subjects and the Dutch Microbiome Project of 7,738 volunteers. Data on plasma metabolites were derived from a GWAS of plasma metabolites in 8,299 participants. Ovarian cancer (n = 25,509) and EOC subtypes were obtained from the Ovarian Cancer Association Consortium (OCAC). Metabolites and associated targets were analyzed via network pharmacology and molecular docking. RESULTS: At the genus and species levels, we identified seven risk factors for the gut microbiota: the genus Dialister (P = 0.024), genus Ruminiclostridium5 (P = 0.0004), genus Phascolarctobacterium (P = 0.0217), species Bacteroides massiliensis (P = 0.011), species Phascolarctobacterium succinatutens (P = 0.0212), species Paraprevotella clara (P = 0.0247) and species Bacteroides dorei (P = 0.0054). In addition, five gut microbes at the genus and species levels were found to be protective: genus Family XIII AD3011 group (P = 0.006), genus ...