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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

Research progress of polyunsaturated fatty acids in inflammatory bowel disease: from mechanisms to treatment

  • Jian-long Zhang1
  • Ying Liu2
  • Jia Liu3,4
  • Wan-neng Yan5
  • Ze Yu1,6
6 affiliations
  1. 1The Laboratory of Cytobiology and Molecular Biology, Zhoushan Hospital, Wenzhou Medical University
  2. 2Department of Pharmacy, Zhoushan Hospital, Wenzhou Medical University
  3. 3School of Agriculture and Biotechnology, Sun Yat-sen University
  4. 4Shenzhen Zhongjia Bio-medical Technology Co., LTD
  5. 5Department of Proctology, Zhoushan Hospital, Wenzhou Medical University
  6. 6Department of Surgery, Zhoushan Hospital, Wenzhou Medical University
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Abstract

Inflammatory bowel disease (IBD) imposes a growing clinical burden through recurrent intestinal inflammation, malnutrition, treatment-related toxicity, and incomplete mucosal healing. Polyunsaturated fatty acids (PUFAs) are plausible dietary regulators of this burden, yet their effects cannot be reduced to a simple anti-inflammatory role for n-3 PUFAs and a pro-inflammatory role for n-6 PUFAs. The proposed pre-clinical concept of PUFA-induced metabolic enteritis links dietary lipid exposure to epithelial stress, lipid peroxidation, and intestinal inflammation in genetically or metabolically susceptible pre-clinical models. Its human counterpart, however, remains incompletely defined. This narrative review integrates evidence across PUFA-derived lipid mediators, the gut microbiota, intestinal barrier function, mucosal immunity, and the glutathione peroxidase 4 (GPX4)-ferroptosis axis. We distinguish observational associations from interventional evidence and examine why clinical trials of eicosapentaenoic acid and docosahexaenoic acid have produced inconsistent results. We also evaluate dietary patterns, PUFA supplements, microbiome-directed approaches, specialized pro-resolving mediators, oxylipin pathways, and soluble epoxide hydrolase inhibition. Current evidence remains pre-clinical. Our review provides an approach and insights for managing IBD before PUFA-directed interventions are incorporated into precision treatment for IBD.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026research,
  title = {{Research progress of polyunsaturated fatty acids in inflammatory bowel disease: from mechanisms to treatment}},
  author = {Jian-long Zhang and Ying Liu and Jia Liu and Wan-neng Yan and Ze Yu},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1971572},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1971572/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Research progress of polyunsaturated fatty acids in inflammatory bowel disease: from mechanisms to treatment
AU  - Jian-long Zhang
AU  - Ying Liu
AU  - Jia Liu
AU  - Wan-neng Yan
AU  - Ze Yu
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1971572
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1971572/full
AB  - Inflammatory bowel disease (IBD) imposes a growing clinical burden through recurrent intestinal inflammation, malnutrition, treatment-related toxicity, and incomplete mucosal healing. Polyunsaturated fatty acids (PUFAs) are plausible dietary regulators of this burden, yet their effects cannot be reduced to a simple anti-inflammatory role for n-3 PUFAs and a pro-inflammatory role for n-6 PUFAs. The proposed pre-clinical concept of PUFA-induced metabolic enteritis links dietary lipid exposure to epithelial stress, lipid peroxidation, and intestinal inflammation in genetically or metabolically susceptible pre-clinical models. Its human counterpart, however, remains incompletely defined. This narrative review integrates evidence across PUFA-derived lipid mediators, the gut microbiota, intestinal barrier function, mucosal immunity, and the glutathione peroxidase 4 (GPX4)-ferroptosis axis. We distinguish observational associations from interventional evidence and examine why clinical trials of eicosapentaenoic acid and docosahexaenoic acid have produced inconsistent results. We also evaluate dietary patterns, PUFA supplements, microbiome-directed approaches, specialized pro-resolving mediators, oxylipin pathways, and soluble epoxide hydrolase inhibition. Current evidence remains pre-clinical. Our review provides an approach and insights for managing IBD before PUFA-directed interventions are incorporated into precision treatment for IBD.
SN  - 1663-9812
ER  -