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Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling

Yuanheng Yang1,2, Cong Hao1, Tingying Jiao3,4

  • 1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.

Science (New York, N.Y.)
|April 3, 2025
PubMed

Insights

A gut-joint axis regulates osteoarthritis via microbial bile acid metabolism. Targeting this pathway with ursodeoxycholic acid (UDCA) may offer a novel treatment for osteoarthritis.

Area of Science:

  • Microbiology
  • Gastroenterology
  • Orthopedics

Background:

  • The existence of a gut-joint axis influencing osteoarthritis (OA) remains unexplored.
  • Alterations in gut microbial bile acid metabolism, specifically reduced glycoursodeoxycholic acid (GUDCA), are observed in OA patients.

Purpose of the Study:

  • To investigate the gut-joint axis in osteoarthritis regulation.
  • To explore the therapeutic potential of modulating gut microbiota and bile acid metabolism for OA treatment.

Main Methods:

  • Analysis of two independent OA cohorts to identify microbial and metabolic alterations.
  • In vivo studies in mice involving suppression or activation of the farnesoid X receptor (FXR) and glucagon-like peptide 1 (GLP-1) pathways.
  • Investigating the role of *Clostridium bolteae* and ursodeoxycholic acid (UDCA) in OA pathogenesis and treatment.
  • Retrospective analysis of human data on UDCA use and OA-related joint replacement risk.

Main Results:

  • Reduced GUDCA levels and altered bile acid metabolism were linked to OA.
  • Suppression of intestinal FXR alleviated OA in mice, mediated by GLP-1.
  • Reduced abundance of *Clostridium bolteae* was observed in OA patients.
  • Administration of *C. bolteae* and UDCA ameliorated OA in mice via the gut FXR-joint GLP-1 axis.
  • Human UDCA use correlated with a decreased risk of OA-related joint replacement.

Conclusions:

  • A novel gut-joint axis involving gut microbiota, bile acid metabolism (GUDCA), intestinal FXR, and joint GLP-1 signaling plays a role in OA.
  • Modulating this pathway, for instance, through UDCA treatment, presents a promising therapeutic strategy for osteoarthritis.

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