We have located links that may give you full text access.
Alteration of gut microbiota in high-risk individuals for rheumatoid arthritis is associated with disturbed metabolome and initiates arthritis by triggering mucosal immunity imbalance.
Arthritis & Rheumatology 2023 May 24
OBJECTIVE: We aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis.
DESIGN: Fecal samples were collected from 38 healthy individuals (HCs) and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA)-positivity (PreRA), 12 of 53 PreRA developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the HC and PreRA individuals or among PreRA subgroups were identified by 16S rRNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice received GM from the HC or PreRA groups were then evaluated for intestinal permeability, inflammatory cytokines and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from PreRA individuals on arthritis severity in mice.
RESULTS: Stool microbial diversity was lower in PreRA individuals than in HCs. The bacterial community structure and function significantly differed between HC and PreRA individuals. Although there were to some extent differences in the bacterial abundance among the PreRA subgroups, no robust functional differences were observed. The metabolites in the serum of the PreRA group were dramatically different from those in the HC group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the PreRA group increased intestinal permeability in FMT mice and ZO-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving PreRA feces compared to HC. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice.
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 arthritis development.
DESIGN: Fecal samples were collected from 38 healthy individuals (HCs) and 53 high-risk RA individuals with anti-citrullinated protein antibody (ACPA)-positivity (PreRA), 12 of 53 PreRA developed RA within 5 years of follow-up. The differences in intestinal microbial composition between the HC and PreRA individuals or among PreRA subgroups were identified by 16S rRNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic-pretreated mice received GM from the HC or PreRA groups were then evaluated for intestinal permeability, inflammatory cytokines and immune cell populations. Collagen-induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from PreRA individuals on arthritis severity in mice.
RESULTS: Stool microbial diversity was lower in PreRA individuals than in HCs. The bacterial community structure and function significantly differed between HC and PreRA individuals. Although there were to some extent differences in the bacterial abundance among the PreRA subgroups, no robust functional differences were observed. The metabolites in the serum of the PreRA group were dramatically different from those in the HC group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the PreRA group increased intestinal permeability in FMT mice and ZO-1 expression in the small intestine and Caco-2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving PreRA feces compared to HC. The changes in intestinal permeability and Th17-cell activation prior to arthritis induction enhanced CIA severity in PreRA-FMT mice compared with HC-FMT mice.
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 arthritis development.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app