Changes in Gut Microbiome Signal Rheumatoid Arthritis Onset

TOPLINE:

Individuals at an increased risk of developing rheumatoid arthritis (RA) have a unique gut microbial composition, characterized by a notable increase in certain strains of Prevotella bacteria. These changes begin approximately 10 months prior to the onset of RA.

METHODOLOGY:

• In this cross-sectional and longitudinal observational study, researchers aimed to identify microbial associations in the early stages of RA, focusing specifically on Prevotellaceae strains.
• The cross-sectional analysis assessed the gut microbiome profiles of 124 individuals at risk of developing RA, seven patients with newly diagnosed RA, and 22 healthy control individuals free of musculoskeletal symptoms at five different time points over a period of 15 months; 30 patients progressed to RA during the study period.
• The longitudinal analysis was performed in 19 individuals at risk of developing RA, of whom five progressed to the condition.
• The risk of developing RA was identified by the presence of anticyclic citrullinated protein (anti-CCP) antibodies and the onset of musculoskeletal pain in the preceding 3 months.
• Gut microbiome taxonomic alterations were investigated using 16S rRNA amplicon sequencing and confirmed with shotgun metagenomic DNA sequencing of 49 samples.

TAKEAWAY:

• Gut microbial diversity, particularly alpha diversity, was notably reduced in CCP+ individuals at risk of developing RA vs healthy control individuals (P = .012). Recognized risk factors for RA development such as the presence of rheumatoid factor antibodies and the human leukocyte antigen shared epitope, were significantly linked to diminished gut microbial diversity, in addition to steroid use.
• A specific Prevotellaceae strain (ASV2058) was found to be overabundant in CCP+ individuals at risk of developing RA and in those newly diagnosed with the condition but not in healthy control individuals. Further analysis showed that enrichment and depletion of three and five strains of Prevotellaceae, respectively, were associated with the progression to RA in CCP+ individuals.
• CCP+ individuals who progressed to RA were found to have substantial fluctuations in gut microbiome profiles around 10 months before clinical diagnosis; however, these profiles were relatively stable 10-15 months before the onset of RA, suggesting that changes in the microbiome occur at a later stage.
• Patients with new-onset RA were found to have distinct metabolic shifts, particularly in pathways related to amino acid and energy metabolism.

IN PRACTICE:

“Individuals at risk of RA harbor a distinctive gut microbial composition, including but not limited to an overabundance of Prevotellaceae species. This microbial signature is consistent and correlates with traditional RA risk factors,” the authors wrote.

SOURCE:

The study was led by Christopher M. Rooney, MD, PhD, University of Leeds, Leeds, England. It was published online on November 7, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The small longitudinal sample size and lack of a 1:1 longitudinal comparison between CCP+ individuals at risk for RA and healthy control individuals were major limitations of this study. The new-onset RA cohort was heterogeneous, reflecting the practical constraints of recruitment from standard care clinics. Integrated transcriptomic or metabolomic data were unavailable, restricting interpretation to potential rather than confirmed metabolic activity.

DISCLOSURES:

This study was funded by personal fellowships received by the lead author from Versus Arthritis, Leeds Cares, and a National Institute for Health Research Clinical Lectureship. Some authors disclosed receiving grants, funding, consulting fees, or honoraria from various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.