The lung microbiota in early rheumatoid arthritis and autoimmunity.

Jose U Scher,Leopoldo N Segal,Alejandro Artacho,Shahla Abdollahi-Roodsaz,Johan Grunewald,Johan Öckinger,Anca I Catrina,Magnus Sköld,Anders Eklund,Susanna Kullberg,Jose C Clemente,Vijay Joshua,Carles Ubeda

doi:10.1186/s40168-016-0206-x

Abstract

BackgroundAirway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. This suggests the possibility that the lung could be a site of autoimmunity generation in RA, perhaps in response to microbiota changes. We therefore sought to test whether the RA lung microbiome contains distinct taxonomic features associated with local and/or systemic autoimmunity.Methods16S rRNA gene high-throughput sequencing was utilized to compare the bacterial community composition of bronchoalveolar lavage fluid (BAL) in patients with early, disease-modifying anti-rheumatic drugs (DMARD)-naïve RA, patients with lung sarcoidosis, and healthy control subjects. Samples were further assessed for the presence and levels of anti-citrullinated peptide antibodies (including fine specificities) in both BAL and serum.ResultsThe BAL microbiota of RA patients was significantly less diverse and abundant when compared to healthy controls, but similar to sarcoidosis patients. This distal airway dysbiosis was attributed to the reduced presence of several genus (i.e., Actynomyces and Burkhordelia) as well as reported periodontopathic taxa, including Treponema, Prevotella, and Porphyromonas. While multiple clades correlated with local and systemic levels of autoantibodies, the genus Pseudonocardia and various related OTUs were the only taxa overrepresented in RA BAL and correlated with higher disease activity and erosions.ConclusionsDistal airway dysbiosis is present in untreated early RA and similar to that detected in sarcoidosis lung inflammation. This community perturbation, which correlates with local and systemic autoimmune/inflammatory changes, may potentially drive initiation of RA in a proportion of cases.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-016-0206-x) contains supplementary material, which is available to authorized users.

Highlights

Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development
Others and we have reported on an analogous dysbiotic process in the intestinal and oral microbiome of RA and psoriatic arthritis (PsA) patients [6,7,8]
When compared to healthy subjects, bronchoalveolar lavage fluid (BAL) microbial alpha-diversity was significantly reduced in both RA and sarcoidosis samples, as calculated by the total number of operational taxonomic units (OTUs) present, the Simpson diversity index, and the Faith’s phylodiversity index (Fig. 1a–c)

Summary

Introduction

Airway abnormalities and lung tissue citrullination are found in both rheumatoid arthritis (RA) patients and individuals at-risk for disease development. Novel concepts in its etiopathogenesis posit that, in the right genetic background (i.e., “shared epitope” alleles), a proportion of these individuals lose tolerance against self-peptides and enter a prolonged autoimmune phase, characterized by the production of circulating autoantibodies [(i.e., rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs)] [1]. These antibodies, arise in the circulation in the absence of major synovial pathology, which has led to a renovated search for extra-articular epigenetic and environmental triggers of disease [2]. Others and we have reported on an analogous dysbiotic process in the intestinal and oral microbiome of RA and psoriatic arthritis (PsA) patients [6,7,8]

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