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

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.