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.
Chen et al. (Fri,) studied this question.