Multitargeted Regulation of Rheumatoid Arthritis by Gut Microbiota

Conventional treatments for Rheumatoid Arthritis (RA) face significant challenges, including high costs, infection risks associated with immunosuppression, and inadequate response in a substantial subset of patients. Recent research into the "gut-joint axis" has revealed that characteristic gut microbiota dysbiosis in RA patients drives disease pathogenesis, spurring the development of novel, safer microbiota-targeting interventions. However, personalized precision intervention and standardization for clinical translation remain critical hurdles. This review systematically analyzes the immune mechanisms underlying RA modulation by gut microbiota, focusing on the roles of pathogenic bacteria and key metabolites like short-chain fatty acids (SCFAs) and tryptophan derivatives in immune homeostasis. It also evaluates the current evidence and research status of diverse intervention strategies, including precision diets with both ecological and diagnostic value, synergistic probiotic effects, the emerging efficacy of fecal microbiota transplantation (FMT), and novel delivery and engineered bacterial technologies, assessing their translational potential. This work provides a new perspective on RA pathogenesis and lays a theoretical foundation for developing cost-effective, high-safety microbiome-immune axis-based therapies for RA. Future research should prioritize developing "microbiota-metabolite-immune phenotype" predictive models to enable precise stratified interventions and accelerate the translation of effective microbiome-targeting therapies.