Gut microbiota in early and established stages of rheumatoid arthritis: from pathogenesis to promising prevention and treatment

Abstract

Background: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Before overt disease, genetically prone individuals may undergo a lengthy pre-clinical phase during which loss of tolerance triggers autoantibody emergence. The gut–joint axis was proposed decades ago, and mounting evidence now suggests that alterations in the gut microbiome may matter most in early, rather than established, RA.Results: By modulating intestinal permeability, mucosal and systemic immunity, genetic-risk pathways, molecular mimicry, and microbial metabolites, the gut microbiota plays a pivotal role in the onset and progression of RA. The window of opportunity for RA therapy may lie before joint inflammation becomes evident, and microbiota-targeted interventions are emerging. Probiotics, dietary interventions, and natural compounds hold promise as potential strategies for both RA prevention and adjunctive therapy after onset.Conclusions: This review highlights the gut microbiota not merely as a modulator of established RA, but–more critically–as a driver of early disease pathogenesis and a promising therapeutic target, thereby providing new insights for managing pre-clinical RA and refining treatment of established RA.