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.

Keywords

16S / chronic pelvic inflammatory disease / metabolomics / metagenomics

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The Author(s). Advanced Chinese Medicine published by John Wiley & Sons Australia, Ltd on behalf of Higher Education Press.