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Bifidobacterium pseudocatenulatum-Mediated Bile Acid Metabolism to Prevent Rheumatoid Arthritis via the Gut-Joint

Qing Zhao1,2,3,4, Huan Ren1,2,3,4, Nian Yang1,2,3,4

  • 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, China.

Nutrients
|January 21, 2023
PubMed

Insights

Probiotics like Bifidobacterium pseudocatenulatum may prevent rheumatoid arthritis (RA) by modulating gut bacteria and bile acids. This approach shows promise for protecting joints and offers a new therapeutic strategy for RA prevention.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Early intervention is crucial for rheumatoid arthritis (RA) treatment, but current pharmacotherapy for preventing joint damage is insufficient.
  • Gut microbiome manipulation offers potential strategies for RA prevention and mitigating joint damage.
  • Bile acids (BAs) and their metabolism are increasingly recognized for their role in immune regulation and inflammatory diseases like RA.

Purpose of the Study:

  • To investigate the mechanisms by which Bifidobacterium pseudocatenulatum influences rheumatoid arthritis (RA).
  • To explore the role of bile acid (BA) metabolism in the protective effects of B. pseudocatenulatum against RA.
  • To identify potential therapeutic targets for RA prevention through probiotic intervention.

Main Methods:

  • 16S rRNA sequencing and UPLC-MS/MS assays were used to analyze gut microbial composition and metabolite profiles.
  • A collagen-induced arthritis (CIA) mouse model was employed to evaluate the efficacy of B. pseudocatenulatum.
  • The involvement of Takeda G protein-coupled receptor 5 (TGR5) was assessed using a specific antagonist (SBI-115).

Main Results:

  • B. pseudocatenulatum administration protected against joint damage in the CIA mouse model by preserving the intestinal barrier.
  • The probiotic reshaped gut microbial composition, increased bile salt hydrolase (BSH) activity, and elevated unconjugated secondary bile acids (BAs).
  • These protective effects were abrogated by the TGR5 antagonist SBI-115, indicating TGR5 mediation.

Conclusions:

  • Bifidobacterium pseudocatenulatum demonstrates potential as a prophylactic agent against rheumatoid arthritis (RA).
  • The mechanism involves the modulation of gut microbiota, enhanced bile acid metabolism, and suppression of aberrant T-helper 1/17 immune responses via TGR5.
  • Prophylactic administration of specific probiotics represents a promising therapeutic avenue for preventing RA and associated joint damage.
Keywords:
Bifidobacterium pseudocatenulatumTakeda G protein-coupled receptor 5Th1/Th17bile acid metabolismgut–joint axisrheumatoid arthritis

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