Multiomics integration of 16S rRNA, metagenomic, and metabolomic analyses unveils gut microbiota–metabolite interactions in Guizhi Fuling capsule‐treated chronic pelvic inflammatory disease rats

Abstract Background Chronic pelvic inflammatory disease (CPID) is a persistent upper reproductive tract disorder characterized by microbial dysbiosis, pelvic adhesions, and infertility. Guizhi Fuling capsule (GZFLC), a multiherb traditional formula, has demonstrated therapeutic potential for CPID. Methods A CPID rat model was established via mixed‐pathogen infection. Evaluations included uterine histopathology, inflammatory cytokine levels (interleukin‐6, tumor necrosis factor‐α, interleukin‐18, interleukin‐1β), coagulation parameters (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen), uterine metabolomics, 16S rRNA sequencing, and metagenomic sequencing to assess microbial composition and functional pathway alterations. Results CPID rats exhibited weight loss, uterine structural damage, elevated inflammation, and a hypercoagulable state. Uterine metabolomics showed significant reductions in key TCA cycle intermediates (α‐ketoglutarate, isocitrate). 16S rRNA sequencing revealed enrichment of the pathogenic bacterium Clostridia_UCG‐014 . Metagenomic analysis indicated upregulation of quorum sensing (QS) pathway genes (thoil‐activated cytolysin, TrbB, Gmr) and downregulation of CAZymes, specifically glycoside hydrolase 2 and carbohydrate esterase 1. Correlation analysis suggested that GZFLC modulates specific microbial taxa, influencing host metabolites and inflammatory responses. Conclusion GZFLC likely alleviates CPID by exerting anti‐inflammatory effects, restoring TCA cycle energy metabolism, reshaping gut microbiota structure, inhibiting QS signaling, and improving polysaccharide metabolic functions.