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

Kelsey N Thompson, Kevin S Bonham, Nicholas E Ilott, Graham J Britton, Paula Colmenero, Samuel J Bullers, Lauren J McIver, Siyuan Ma, Long H Nguyen, Andrew Filer, India Brough, Claire Pearson, Caroline Moussa, Vinod Kumar, Lilian H Lam, Matthew A Jackson, April Pawluk, Serafim Kiriakidis, Peter C Taylor, Lucy R WedderburnBrian D Marsden, Stephen Young, Dan R Littman, Jeremiah J Faith, Arthur G. Pratt, Paul Bowness, Karim Raza, Fiona Powrie, Curtis Huttenhower*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

173 Downloads (Pure)

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.
Original languageEnglish
Article number eabn47
Number of pages16
JournalScience Translational Medicine
Volume15
DOIs
Publication statusPublished - 26 Jul 2023

Fingerprint

Dive into the research topics of 'Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes'. Together they form a unique fingerprint.

Cite this