Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation that are reversed by inflammation control

Abstract

Abstract Objective To assess how RA and DMARDs affect gut permeability. Methods To explore colonic mucosa integrity, tight junction proteins zonula occludens-1, occludin and claudin 2 were quantified by immunohistochemistry on colonic biopsies in 20 RA patients and 20 age- and sex-matched controls. Staining intensity was assessed by two blinded independent readers. To explore intestinal permeability, serum concentrations of lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and zonulin-related proteins (ZRPs) were evaluated by ELISA in another cohort of 59 RA patients: 21 patients naive for DMARDs [17 before and after introduction of a conventional synthetic DMARD (csDMARD)], 38 patients with severe RA [before and after introduction of a biological DMARD (bDMARD)] and 33 healthy controls. Results Z0-1 protein was less expressed in the colon of RA patients than controls [mean score 1.6 (s.e.m. 0.56) vs 2.0 (0.43), P = 0.01], while no significant difference was detected for occludin and claudin-2. RA patients had higher serum LBP and sCD14 concentrations than controls. LBP and sCD14 levels were significantly correlated with the 28-joint DAS (r = 0.61, P = 0.005 and r = 0.57, P = 0.01, respectively) while ZRP did not. bDMARD responders had significantly reduced LBP and sCD14 concentrations, unlike bDMARD non-responders and patients treated with csDMARDs. Conclusion RA patients have altered colonic tight junction proteins and increased serum biomarkers of intestinal permeability. There was a correlation between serological markers of intestinal permeability and disease activity as well as bDMARD response. These results suggest a link between impaired gut integrity and systemic inflammation in RA.