Alteration of Gut Microbiota in Individuals at High‐Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance
Authors' conclusion
Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.
Study context
- Population
- Healthy individuals and anti-citrullinated protein antibody (ACPA)-positive individuals at high risk for rheumatoid arthritis (RA); mice receiving fecal microbiota transplantation (FMT)12 of 53 Pre-RA developed RA within 5 years
- Participants
- 53 vs 38
- Comparison
- Pre-RA (ACPA-positive high-risk) individuals vs healthy controls; FMT from Pre-RA vs healthy controls in mice
- Pre-RAn = 53
- Healthy controlsn = 38reference
Methodological details16S rRNA sequencing, serum metabolomics, fecal microbiota transplantation in antibiotic-pretreated mice, collagen-induced arthritis model
- 16S rRNA sequencing
- Serum metabolomics
- Fecal microbiota transplantation in antibiotic-pretreated mice
- Collagen-induced arthritis model
Main finding
As reported in the abstract
- Stool microbial diversity lower in Pre-RA than healthy controls
- Bacterial community structure and function significantly differed between healthy controls and Pre-RA
- Among Pre-RA subgroups, some differences in bacterial abundance but no robust functional differences
- Serum metabolites of Pre-RA dramatically different from healthy controls, with KEGG enrichment of amino acid and lipid metabolism
- Pre-RA intestinal bacteria increased intestinal permeability in FMT mice and zonula occludens-1 expression in small intestine and Caco-2 cells
- Th17 cells in mesenteric lymph nodes and Peyer's patches increased in mice receiving Pre-RA feces vs healthy controls
- Collagen-induced arthritis (CIA) severity enhanced in PreRA-FMT vs HC-FMT mice
Original publication
Alteration of Gut Microbiota in Individuals at High‐Risk for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance. Arthritis Rheumatol. Published 21 September 2023. doi:10.
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