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ORIGINAL RESEARCH article

Front. Microbiomes

Sec. Omics and Bioinformatics for Microbiomes

Volume 4 - 2025 | doi: 10.3389/frmbi.2025.1531991

This article is part of the Research TopicGut Microbiota Modulation to Mitigate Stress-Induced Functional ChangesView all 12 articles

Cold-water immersion alleviates exertional heat stroke-induced intestinal damage by modulating gut microbiota in rats

Provisionally accepted
Lyv  XuanLyv Xuan1,2*Xiaojun  SunXiaojun Sun2*Baozhong  WangBaozhong Wang2Feng  ChenFeng Chen3Yuhao  YiYuhao Yi3Handing  MaoHanding Mao4Yuxi  WangYuxi Wang1Guifeng  ZhaoGuifeng Zhao3*Jiaxing  WangJiaxing Wang1*Yuxiang  ZhangYuxiang Zhang1*
  • 1Department of Pulmonary and Critical Care Medicine, Eighth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing, China
  • 2hospital of armed police force, Harbin, China
  • 3Department of Critical Care Medicine, Department of Ophthalmology, PLA Rocket Force Characteristic Medical Center, Beijing, China
  • 4Department of Emergency, Sixth Medical Center of PLA General Hospital, Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

The pathogenesis of exertional heatstroke (EHS) involves significant contributions from gut microbiota and their metabolites. To assess whether cold-water immersion (CWI) mitigates EHS-induced intestinal damage via microbiome alterations, an EHS model was created in 18 Wistar rats, divided into three groups: the EHS group (rats with exertional heatstroke), the CWI group (rats with heatstroke treated with cold-water immersion), and the CTRL group (rats with normothermia control). Evaluations included pathological changes, core temperature (Tcore), and levels of lactic acid (Lac) and endotoxin lipopolysaccharide (LPS). Fecal samples underwent metagenomic shotgun sequencing and liquid chromatography-mass spectrometry for microbiota and metabolomic profiling. Hematoxylin & eosin staining showed that CWI treatment significantly reduced EHS-induced intestinal congestion, edema, and necrosis compared to the EHS group. The EHS group had the highest Tcore, while the CWI group had significantly lower Tcore compared to the EHS group. Additionally, the CWI group exhibited significantly reduced LPS and Lac levels, nearing those of the CTRL group. Microbiome analysis indicated that EHS disrupted gut bacteria, with increased pathogens like Desulfovibrio fairfieldensis, Desulfamplus magnetovallimortis, and Desulfococcus oleovorans (P<0.05). CWI treatment resolved these disturbances, restoring gut microbiota similar to the control group. In addition, Metagenomic analysis revealed that CWI restored gut microbiota diversity (Shannon index: EHS 3.2±0.4 vs. CWI 4.1±0.3, P<0.05), significantly reducing pathogenic Desulfovibrio (relative abundance: EHS 8.7% vs. CWI 2.1%). Metabolomic profiling identified key metabolites such as inosine, hypoxanthine, guanosine, and taurine (Variable importance in projection>1, P<0.05 with P-values adjusted for multiple comparisons using the Benjamini-Hochberg method, FDR<0.05), distinguishing the CWI and EHS groups. These metabolites, inosine, taurine, hypoxanthine, and guanosine, correlate with restored gut microbiota, reduced Desulfovibrio, and attenuated inflammation (lower LPS/Lac), suggesting their dual role in mitigating intestinal damage. These findings underscore the therapeutic potential of CWI through modulation of microbial-derived metabolites, highlighting its impact on intestinal health in EHS.

Keywords: Exertional heat stroke, Gut Microbiota, Metabolic disorder, cold-water immersion, lipopolysaccharide

Received: 21 Nov 2024; Accepted: 19 Aug 2025.

Copyright: © 2025 Xuan, Sun, Wang, Chen, Yi, Mao, Wang, Zhao, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Lyv Xuan, Department of Pulmonary and Critical Care Medicine, Eighth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing, China
Xiaojun Sun, hospital of armed police force, Harbin, China
Guifeng Zhao, Department of Critical Care Medicine, Department of Ophthalmology, PLA Rocket Force Characteristic Medical Center, Beijing, China
Jiaxing Wang, Department of Pulmonary and Critical Care Medicine, Eighth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing, China
Yuxiang Zhang, Department of Pulmonary and Critical Care Medicine, Eighth Medical Center of the General Hospital of the Chinese People's Liberation Army, Beijing, China

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