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Peer-reviewedCC BY 4.0Frontiers in Immunology

Gut epithelial barriers as regulators of metabolite-driven immune responses

  • Anuradha Tyagi1
  • Rajul Tayal2
  • Dharmendra Nath Bhatt3
  • Shivani Srivastava4
  • Anil Kumar5
  • Antresh Kumar6
  • Vinay Kumar1
6 affiliations
  1. 1College of Medicine, Pennsylvania State University Hershey Medical Centre
  2. 2National Institute of Plant Genome Research
  3. 3Molecular Pathology Section, Laboratory of Immunogenetics, Division of Intramural Research/National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH)
  4. 4Department of Cellular and Molecular Physiology, Yale University School of Medicine
  5. 5University Centre for Research and Development, Chandigarh University
  6. 6Department of Biochemistry, Central University of Haryana
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Abstract

Immunometabolism provides a framework for understanding how metabolic cues shape immune cell fate and function. While traditionally centered on cell-intrinsic pathways, emerging evidence highlights a critical role for epithelial barrier regulation in shaping immune responses by controlling exposure to microbiome derived metabolites. Microbial metabolites including short-chain fatty acids, bile acid derivatives, tryptophan catabolites, and polyamines engage conserved metabolic checkpoints such as mTOR, AMPK, PPARs, SIRT1, and HIF-1α to influence immune activation, tolerance, and inflammatory tone. Critically, epithelial barriers regulate immune exposure to these signals, positioning barrier integrity as an upstream determinant of immunometabolic reprogramming. Altered epithelial metabolism compromises tight junction stability and metabolite flux, contributing to dysregulated immune activation and chronic inflammation. In this review, we synthesize current evidence supporting the concept that epithelial barriers act as metabolic gatekeepers of immunity, integrating microbial signals with host metabolic pathways to regulate immune function and disease susceptibility.

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Cite

BibTeXRIS
BibTeX
@article{tyagi2026epithelial,
  title = {{Gut epithelial barriers as regulators of metabolite-driven immune responses}},
  author = {Anuradha Tyagi and Rajul Tayal and Dharmendra Nath Bhatt and Shivani Srivastava and Anil Kumar and Antresh Kumar and Vinay Kumar},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1959305},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959305/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Gut epithelial barriers as regulators of metabolite-driven immune responses
AU  - Anuradha Tyagi
AU  - Rajul Tayal
AU  - Dharmendra Nath Bhatt
AU  - Shivani Srivastava
AU  - Anil Kumar
AU  - Antresh Kumar
AU  - Vinay Kumar
PY  - 2026
DA  - 2026/10/27
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1959305
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1959305/full
AB  - Immunometabolism provides a framework for understanding how metabolic cues shape immune cell fate and function. While traditionally centered on cell-intrinsic pathways, emerging evidence highlights a critical role for epithelial barrier regulation in shaping immune responses by controlling exposure to microbiome derived metabolites. Microbial metabolites including short-chain fatty acids, bile acid derivatives, tryptophan catabolites, and polyamines engage conserved metabolic checkpoints such as mTOR, AMPK, PPARs, SIRT1, and HIF-1α to influence immune activation, tolerance, and inflammatory tone. Critically, epithelial barriers regulate immune exposure to these signals, positioning barrier integrity as an upstream determinant of immunometabolic reprogramming. Altered epithelial metabolism compromises tight junction stability and metabolite flux, contributing to dysregulated immune activation and chronic inflammation. In this review, we synthesize current evidence supporting the concept that epithelial barriers act as metabolic gatekeepers of immunity, integrating microbial signals with host metabolic pathways to regulate immune function and disease susceptibility.
SN  - 1664-3224
ER  -