Rooney, CM, Mankia, K, Mitra, S orcid.org/0000-0002-9378-1496 et al. (3 more authors) (2020) Perturbations of the gut microbiome in anti-CCP positive individuals at risk of developing rheumatoid arthritis. Rheumatology. ISSN 1462-0324
Abstract
Objective
Individuals with newly diagnosed RA have a distinct microbiome when compared with healthy controls. However, little is known as to when these microbiome perturbations begin. Using a prospective at-risk cohort of individuals positive for anti-citrullinated protein (anti-CCP) antibody with new onset musculoskeletal symptoms, but without clinical arthritis, we investigated for the presence of a gut dysbiosis before the onset of RA.
Methods
The gut microbiota of 25 anti-CCP positive individuals without clinical synovitis were sequenced targeting the V4 region of the 16S rRNA gene. Using a publicly available database, a control population of 44 individuals, approximately matched in age, gender, diet and ethnicity was selected for comparison, using the same sequencing methodology. Median interval between sample collection and progression to RA was 188 days. Taxonomic analysis was performed using QIIME and MEGAN, and statistical analysis using R software.
Results
There were significant differences (P =0.01) at family level in gut microbiomes of anti-CCP positive individuals vs controls. The anti-CCP positive population had an overabundance of Lachnospiraceae, Helicobacteraceae, Ruminococcaceae, Erysipelotrichaceae and Bifidobacteriaceae, among others. Five individuals progressed to RA between sample collection and analysis. Clustering of the progressor population was observed on a phylogenetic network created using a probabilistic similarity index (Goodall’s index).
Conclusions
Anti-CCP positive at-risk individuals without clinical synovitis appear to have a distinct gut microbiome compared with healthy controls. Phylogenetic clustering was observed in individuals who progressed to RA, suggesting that distinct taxa are associated with the development of RA many months before its onset.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an author produced version of a journal article published in Rheumatology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | gut microbiome, pre-rheumatoid arthritis, 16S rRNA sequencing, microbial dysbiosis |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Nov 2020 14:59 |
Last Modified: | 11 Dec 2021 01:38 |
Status: | Published online |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/rheumatology/keaa792 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:167767 |