Higher serum levels of short-chain fatty acids are associated with non-progression to arthritis in individuals at increased risk of RA.

Transition from the autoimmune to the clinical phase of rheumatoid arthritis (RA) is a critical step that is yet insufficiently understood. Identification of factors that facilitate the progression from this prodromal RA at-risk state to clinical RA may open new possibilities for preventive interventions. In this context, nutritional factors may be critical. Short-chain fatty acids (SCFAs) are intestinal microbial metabolites that result from nutritional fibre digestion and exert immune regulatory properties.1 SCFAs have shown to effectively inhibit the onset of experimental arthritis.2 Furthermore, serum butyrate levels decrease shortly before the onset of arthritis.2 Whether SCFA levels may play a role in the transition from the autoimmune to the clinical phase of RA in humans, however, has not been studied to date. To address this concept, we measured serum SCFA levels in a prospective cohort of 82 individuals with an increased risk to develop RA.3 At inclusion, these individuals were positive for anti-citrullinated protein antibodies (ACPA) and had musculoskeletal pain but no clinical signs of arthritis (joint swelling). Baseline characteristics are shown in online supplemental table 1. Following a median follow-up of 72 months, 39 patients (48%) had developed clinical arthritis after a median of 6 months. Baseline serum samples were analysed for SCFA …