Gut microbiota in rheumatoid arthritis: Mechanistic insights, clinical biomarkers, and translational perspectives

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease shaped by complex interactions between genetics and environmental factors, among which gut microbiota has emerged as a critical modulator. Recent advances have implicated gut microbiota dysbiosis in RA pathophysiology, with evidence spanning mechanistic, diagnostic, and therapeutic dimensions. This review summarizes current knowledge of the gut-joint axis and outlines microbiota-based strategies for RA management. Numerous studies have demonstrated consistent alterations in gut microbial communities in patients with RA, with enrichment of Prevotella copri observed in 75% of patients with new-onset RA compared to 21.4% of healthy controls, suggesting a potential association with disease initiation. Mechanistically, we detail how microbial dysbiosis, including that of bacteria, fungi, and viruses, disrupts intestinal barrier integrity, skews T helper 17/T regulatory and T follicular helper/T follicular regulatory immune axes, induces molecular mimicry, and alters the profiles of microbial metabolites such as short-chain fatty acids. Diagnostically, microbial taxa and metabolites serve as promising biomarkers. Machine learning models based on microbiota profiles have achieved area under the curve (AUC) values exceeding 0.88, with discriminatory taxa such as Ruminococcus gnavus and Fusicatenibacter. Therapeutically, we reviewed microbiota-targeted interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, diet, and herbal medicines, highlighting the emerging field of pharmacomicrobiomics. Gut microbial signatures have shown promise in predicting treatment responses, including methotrexate efficacy via the enterotype-based gut microbial human index model (AUC = 0.945). This review proposes an integrated framework linking microbial alterations with RA onset and progression and presents gut microbiota as a promising frontier for biomarker discovery, personalized intervention, and precision medicine.