Multi-omics based mechanistic study of Fufang Xuelian capsule in treating ankylosing spondylitis via the gut-joint axis.

Abstract

Ankylosing spondylitis (AS) is a systemic autoimmune disease closely associated with gut microbiota dysbiosis. Fufang Xuelian Capsule (FXLC) has demonstrated clinical efficacy in treating AS; however, its underlying mechanism of action remains unclear. This study aimed to elucidate whether FXLC alleviates AS by modulating the gut-joint axis. Proteoglycan induced ankylosing spondylitis (PGIA) mouse model as the research object. An multi-omics approach, including 16S rRNA sequencing, untargeted serum metabolomics, and synovial tissue proteomics, was employed to evaluate the effects of FXLC on gut microbiota, metabolic profiles, and joint protein expression. FXLC treatment significantly ameliorated arthritic symptoms, reduced serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-23), and restored intestinal barrier integrity. FXLC remodeled the gut microbiota structure, notably reducing the relative abundance of Prevotella and enriching the beneficial genus Lactobacillus. These microbial changes were accompanied by a systemic correction of metabolic disturbances, particularly in the tryptophan and bile acid metabolism pathways. Synovial proteomics revealed that FXLC downregulated potential target proteins, MAPK14 and MMP9. Our research findings indicate that the FXLC can exert anti-AS effects by regulating the gut-joint axis. This process involves remodeling of the intestinal microbiota, reprogramming of the tryptophan and bile acid metabolic pathways, and down-regulation of the expression of synovial-related proteins such as MAPK14 and MMP9. As a result, it effectively alleviates joint inflammation and achieves intestinal protection. These findings provide a mechanistic framework and testable hypotheses to support further investigation into the clinical application of FXLC.