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Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Lookup NU author(s): Dr Arthur PrattORCiD

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Abstract

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.


Publication metadata

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

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

PubMed id: 37494472


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Funding

Funder referenceFunder name
21226
21593
22072
Centre for Adolescent Rheumatology Versus Arthritis
Judith and Stewart Colton Center for Autoimmunity
NIHR Great Ormond Street BRC
NIHR Oxford Biomedical Research Centre
NIHR Birmingham BRC
NIHR Newcastle BRC
Research into Inflammatory Arthritis Versus Arthritis
Versus Arthritis

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