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Microbial-purine metabolic crosstalk regulates colitis-related intestinal fibrosis: A multiomics and cohort analysis

Xiaoxuan Mai1, Jinzhen Wu1, Zhenyi Tian1

  • 1Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, PR China.

The Journal of Nutritional Biochemistry
|June 15, 2025
PubMed

Insights

Altered gut microbes and purine metabolism, specifically elevated uric acid (UA), are linked to intestinal fibrosis (IF) in inflammatory bowel disease (IBD). High serum UA and UA/creatinine (UA/Cr) may predict disease activity and stenosis.

Area of Science:

  • Gastroenterology
  • Microbiome Research
  • Metabolomics

Background:

  • Intestinal fibrosis (IF) is a serious complication of inflammatory bowel disease (IBD).
  • The connection between gut microbes, metabolism, and IF is not well understood.
  • Identifying biomarkers for IF progression is crucial for patient management.

Purpose of the Study:

  • To investigate microbiome-metabolome interactions in IBD-associated IF.
  • To identify potential metabolic biomarkers for IF progression and stenosis.

Main Methods:

  • 16S rRNA sequencing and metabolomics on IBD patients (n=109) and healthy controls (n=111).
  • Murine models of IF were used to study disease progression.
  • Correlation analyses linked microbial and metabolic profiles with clinical and endoscopic disease markers.

Main Results:

  • Gut microbiome alterations included reduced uric acid (UA)-degrading microbes and increased hyperuricemia-associated taxa.
  • Purine metabolism was impaired, with elevated fecal, colonic, and serum UA levels in IBD patients.
  • Serum UA and UA/creatinine (UA/Cr) levels were significantly higher in IBD patients and correlated with disease activity and stenosis, particularly in Crohn's disease.

Conclusions:

  • Abnormal purine metabolism, involving specific microbes and metabolites, plays a role in IBD-associated intestinal fibrosis.
  • Elevated serum UA and UA/Cr are promising biomarkers for assessing disease activity and predicting stenosis in IBD patients.
Keywords:
BiomarkersInflammatory bowel diseaseIntestinal fibrosisPurine metabolismUric acid

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