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

Rachel Audo (1, 2) , Pauline Sanchez (2, 3) , Benjamin Rivière (2, 3) , Julie Mielle (4) , Jian Tan (4) , C. Lukas (5, 6, 7) , Laurence Macia (4) , Jacques Morel (2, 1) , Claire Immediato Daien (1, 2)

1 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 UM - Université de Montpellier
4 The University of Sydney
5 AIDMP - Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415
6 University Hospital of Montpellier
7 IDESP - Institut Desbrest de santé publique

Objective: to assess how rheumatoid arthritis (RA) and Disease Modifying Anti Rheumatic Drugs (DMARDs) affect gut permeability. Methods to explore colonic mucosa integrity, tight junction proteins ZO-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 LPS-binding protein (LBP), sCD14 and zonulin-related proteins (ZRP) were evaluated by ELISA in another cohort of 59 RA: 21 patients naive of DMARDs (17 before and after introduction of a conventional synthetic (cs) DMARDs), 38 patients with severe RA (before and after introduction of a biological (b) DMARDs), and 33 healthy controls. Results: Z0-1 protein was less expressed in colon of RA patients than controls (mean score ± SEM of 1.6 ± 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 DAS28 (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 bDMARDs 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.

Mots clés: DMARDs; gut homeostasis; gut permeability; microbiota; rheumatoid arthritis

Domaines: Rhumatologie et système ostéo-articulaire

Rachel Audo, Pauline Sanchez, Benjamin Rivière, Julie Mielle, Jian Tan, et al.. Rheumatoid arthritis is associated with increased gut permeability and bacterial translocation which are reversed by inflammation control. Rheumatology, In press, ⟨10.1093/rheumatology/keac454⟩. ⟨hal-03750551⟩