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

Rachel Audo; Pauline Sanchez; Benjamin Rivière; Julie Mielle; Jian Tan; Cédric Lukas; Laurence Macia; Jacques Morel; Claire Immediato Daien

doi:10.1093/rheumatology/keac454

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

Rheumatology (Oxford). 2022 Aug 10:keac454. doi: 10.1093/rheumatology/keac454. Online ahead of print.

Authors

Rachel Audo^{1

2}, Pauline Sanchez¹, Benjamin Rivière³, Julie Mielle⁴, Jian Tan⁴, Cédric Lukas¹, Laurence Macia⁴, Jacques Morel^{1

2}, Claire Immediato Daien^{1

2}

Affiliations

¹ Department of Rheumatology, Montpellier University Hospital (CHRU), University Of Montpellier, Montpellier, France.
² University of Montpellier, PhyMedExp, Inserm U1046, CNRS UMR 9214, Montpellier, FRANCE.
³ Department of pathology and onco-biology, CHRU Montpellier, University Of Montpellier, Montpellier, France.
⁴ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.

PMID: 35946514
DOI: 10.1093/rheumatology/keac454

Abstract

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.

Keywords: DMARDs; gut homeostasis; gut permeability; microbiota; rheumatoid arthritis.