Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome
5 affiliations
- 1Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University
- 2Department of General surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University
- 3Department of General Surgery, The First Affiliated Hospital of USTC
- 4Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University
- 5Central Laboratory and Department of Medical Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Abstract
Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.
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BibTeX
@article{yang2026ketogenic,
title = {{Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome}},
author = {Jingjing Yang and Zhi Ling and Ming Zhou and Mingyang Tao and Jingxian Mao and Huaijuan Guo and Jiaxin Wang and Xiao Qu and Ying Wang and Yefei Zhu and Kun Zhang and Xuebing Yan},
journal = {Communications Biology},
year = {2026},
month = jun,
doi = {10.1038/s42003-026-10546-9},
url = {https://doi.org/10.1038/s42003-026-10546-9},
note = {CC BY},
}
RIS
TY - JOUR
TI - Ketogenic diet alleviates acute radiation-induced intestinal injury through JAK2/STAT3/RORγt/IL-17A signaling pathway via gut microbiome
AU - Jingjing Yang
AU - Zhi Ling
AU - Ming Zhou
AU - Mingyang Tao
AU - Jingxian Mao
AU - Huaijuan Guo
AU - Jiaxin Wang
AU - Xiao Qu
AU - Ying Wang
AU - Yefei Zhu
AU - Kun Zhang
AU - Xuebing Yan
PY - 2026
DA - 2026/06/01
JO - Communications Biology
DO - 10.1038/s42003-026-10546-9
UR - https://doi.org/10.1038/s42003-026-10546-9
AB - Emerging evidence suggests dietary interventions regulate inflammatory signaling through gut microbiome modulation, yet their therapeutic potential in radiation-induced intestinal injury (RIII) remains underexplored. This study demonstrates that ketogenic diet (KD), a high-fat and low-carbohydrate dietary regimen, exerts protective effects against RIII through dual mechanisms involving microbial regulation and inflammatory pathway inhibition. Using high-salt diet (HSD) as a dietary control, KD significantly attenuated intestinal inflammation by downregulating pro-inflammatory cytokines while enhancing barrier integrity through tight junction protein upregulation in radiation-exposed murine model. 16S rDNA sequencing showed KD enriched Akkermansia and reduced Enterobacteriaceae, whereas HSD exhibited inverse patterns. Mechanistically, RNA sequencing revealed that KD uniquely suppressed the JAK2/STAT3 pathway in RIII mice. In vitro studies demonstrated that β-hydroxybutyrate, a key ketone metabolite, effectively suppressed RORγt expression and subsequent downregulation of IL-17A gene transcription via the inhibition of JAK2/STAT3 pathway, thus mitigate inflammatory damage. Fecal microbiota transplantation validated that KD-modified microbiome directly inhibited JAK2/STAT3 signaling activation, as well as the downregulation of RORγt and IL-17A. These findings establish KD as a promising dietary strategy mitigate acute RIII through synergistic modulation of gut microbiota and inflammatory signaling, providing novel insights into nutritional approaches targeting microbial-host crosstalk in radiation injury.
SN - 2399-3642
ER -