Integrative analysis of gut microbiome and serum metabolomics explores the therapeutic mechanism of tongfeng qingxiao prescription in treating gouty arthritis

Abstract

Gouty arthritis (GA), a metabolic inflammatory disorder, shows increasing global prevalence, especially in China. Conventional GA treatments often cause adverse reactions, necessitating alternative therapies. Tongfeng Qingxiao Prescription (TFQXP) demonstrates clinical efficacy in GA, though its mechanisms remain unclear. This research explored TFQXP's effects in GA rats using gut microbiome and serum metabolomics analyses. Sprague-Dawley rats (n = 36) were randomly divided into six groups: control, model, TFQXP low-dose, medium-dose, high-dose, and positive groups. GA was induced in all groups except the control group and confirmed via gait analysis and infrared thermal imaging. Inflammation was assessed by measuring ankle joint edema. Histopathology evaluated colon and ankle joint tissues, while transmission electron microscopy examined intestinal epithelium. Mucin 2 expression was analyzed via immunohistochemistry. Synovial TLRs/MyD88/NF-κB pathway components were evaluated using western blotting and qRT-PCR. Gut microbiota structure was assessed via 16S rDNA sequencing, while serum metabolites were analyzed using non-targeted metabolomics. Multi-omics correlation analyses explored gut microbiota-serum metabolite relationships. TFQXP appears to mitigate GA-induced synovial and cartilage damage by suppressing the TLRs/MyD88/NF-κB signaling pathway, resulting in downregulation of pro-inflammatory mediators. Furthermore, TFQXP promoted intestinal barrier repair, alleviated dysbiosis, and ameliorated metabolic pathway dysregulation. Thus, TFQXP may exert therapeutic effects on GA by modulating the "gut-joint" axis.