A comparison of the composition of the gut microbiota of 50 first-degree relatives of patients with rheumatoid arthritis (RA; autoantibody-negative and asymptomatic) and 83 individuals with pre-clinical RA (autoantibody-positive and/or symptomatic) revealed a significant enrichment of Prevotella species in the guts of those with pre-clinical RA (P = 0.04). These results indicate that increases in the prevalence of Prevotella species, previously noted in the guts of newly diagnosed patients with RA, could actually precede the onset of disease, and lend support to the mucosal origins hypothesis for RA.