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Propionate alleviates ulcerative colitis by modulating the PI3K/AKT signaling pathway and suppressing NLRP3 inflammasome activation

  • 0Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, China.
Food & Function +

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August 15, 2025

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August 15, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Propionate, a short-chain fatty acid, effectively treats ulcerative colitis by reducing inflammation. It works by inhibiting the NLRP3 inflammasome pathway, offering a new therapeutic target for inflammatory diseases.

Area Of Science

  • Gastroenterology
  • Immunology
  • Molecular Biology

Background

  • Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
  • Short-chain fatty acids (SCFAs), like propionate, show potential in mitigating colitis, but mechanisms are unclear.
  • The NLRP3 inflammasome is implicated in UC pathogenesis.

Purpose Of The Study

  • To investigate the therapeutic effects of propionate in dextran sulfate sodium (DSS)-induced colitis.
  • To elucidate propionate's regulatory role on NLRP3 inflammasome activation and signaling pathways.
  • To explore the involvement of G-protein coupled receptor 43 (GPR43) in propionate's action.

Main Methods

  • Utilized two models of DSS-induced colitis in vivo.
  • Conducted in vitro experiments using the RAW264.7 macrophage cell line.
  • Assessed NLRP3 inflammasome activation, pro-inflammatory cytokine levels, epithelial barrier integrity, and PI3K/AKT signaling.

Main Results

  • Propionate administration significantly ameliorated DSS-induced colitis.
  • Propionate suppressed NLRP3 inflammasome activation, reducing pro-inflammatory factors.
  • Restoration of epithelial barrier function and downregulation of the PI3K/AKT pathway were observed.
  • These effects were mediated via GPR43 activation.

Conclusions

  • Propionate is a potent therapeutic agent for ulcerative colitis by suppressing NLRP3 inflammasome activation.
  • The propionate-NLRP3 axis represents a novel therapeutic target for inflammatory diseases.
  • This study opens new avenues for UC treatment strategies.

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