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Lookup NU author(s): Dr Arthur PrattORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis.
Author(s): Thompson KN, Bonham KS, Ilott NE, Britton GJ, Colmenero P, Bullers SJ, McIver LJ, Ma S, Nguyen LH, Filer A, Brough I, Pearson C, Moussa C, Kumar V, Lam LH, Jackson MA, Pawluk A, Kiriakidis S, Taylor PC, Wedderburn LR, Marsden B, Young SP, Littman DR, Faith JJ, Pratt AG, Bowness P, Raza K, Powrie F, Huttenhower C
Publication type: Article
Publication status: Published
Journal: Science Translational Medicine
Year: 2023
Volume: 15
Issue: 706
Online publication date: 26/07/2023
Acceptance date: 22/06/2023
Date deposited: 29/05/2024
ISSN (print): 1946-6234
ISSN (electronic): 1946-6242
Publisher: American Association for the Advancement of Science (AAAS)
URL: https://doi.org/10.1126/scitranslmed.abn4722
DOI: 10.1126/scitranslmed.abn4722
ePrints DOI: 10.57711/4w6v-wz62
Data Access Statement: All data associated with this study are in the paper or Supplementary Materials. Sequence data and metadata are available for approved users to download through the EGA (https://ega-archive.org/), study accession number EGAS00001005525. Processed taxonomic and functional tables are available in data file S1. Bioinformatic workflows for metagenomic processing are available at are part of the bioBakery workfllows (122); these include some basic statistical and visualization scripts. Custom analysis scripts are available for this analysis are available through Zenodo (doi 10.5821/zenodo.8010018).
PubMed id: 37494472
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