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Glycocholic acid inhibits TRIB3-ID1 axis to acelerate colitis progression via suppressing intestinal stem cell

Shuang Shang1,2,3, Jing Liu4, Shu-Yuan Dai4

  • 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China. shangshuang@imm.ac.cn.

Nature Communications
|July 11, 2026
PubMed

Insights

Glycocholic acid worsens inflammatory bowel disease by harming intestinal stem cells. Bergenin, a natural compound, may treat inflammatory bowel disease by boosting TRIB3 expression and protecting stem cells.

Area of Science:

  • Gastroenterology
  • Stem Cell Biology
  • Molecular Medicine

Background:

  • Intestinal stem cell function is vital for mucosal healing in inflammatory bowel disease (IBD).
  • Altered bile acid metabolism, with elevated fecal glycocholic acid, is observed in IBD, but its role is unclear.
  • Understanding molecular mechanisms impairing intestinal stem cells in IBD is key for novel therapeutics.

Purpose of the Study:

  • To investigate the role of glycocholic acid in inflammatory bowel disease (IBD) pathogenesis.
  • To elucidate the molecular mechanisms by which glycocholic acid affects intestinal stem cells.
  • To identify potential therapeutic targets for IBD.

Main Methods:

  • Investigated the effect of glycocholic acid on intestinal stem cell self-renewal in an IBD model.
  • Analyzed the expression of TRIB3 and its interaction with ID1.
  • Assessed the therapeutic potential of Bergenin in modulating the TRIB3-ID1 axis.

Main Results:

  • Glycocholic acid accelerates IBD progression by downregulating TRIB3 expression, disrupting intestinal stem cell self-renewal.
  • TRIB3 normally prevents ID1 palmitoylation and lysosomal degradation, maintaining intestinal epithelial stemness.
  • Glycocholic acid suppresses the TRIB3-ID1 axis, compromising intestinal epithelium integrity.
  • Bergenin was identified as a natural compound that upregulates TRIB3, showing potential for IBD therapy.

Conclusions:

  • The TRIB3-ID1 axis is crucial for maintaining intestinal stemness and epithelial integrity.
  • Glycocholic acid exacerbates IBD by disrupting the TRIB3-ID1 pathway, impairing stem cell function.
  • Bergenin emerges as a potential therapeutic agent for IBD by restoring TRIB3 expression and function.

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