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Exercise training at different intensities induces heat stress, disrupts barrier function and alters microbiota in the gut of mice

Puqiao Lian, Artemiy Kovynev, Lei Wang, Amanda C. M. Pronk, Aswin Verhoeven, View ORCID ProfileMartin Giera, Suzan Thijssen, Borja Martínez Téllez, View ORCID ProfileSander Kooijman, View ORCID ProfilePatrick C. N. Rensen, Harro Timmerman, Harry J. Wichers, View ORCID ProfilePaul A. J. Henricks, Gert Folkerts, Milena Schönke, View ORCID ProfileSaskia Braber
doi: https://doi.org/10.1101/2024.07.10.602866
Puqiao Lian
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
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Artemiy Kovynev
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Lei Wang
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
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Amanda C. M. Pronk
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Aswin Verhoeven
4Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Martin Giera
4Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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  • ORCID record for Martin Giera
Suzan Thijssen
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
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Borja Martínez Téllez
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Sander Kooijman
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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  • ORCID record for Sander Kooijman
Patrick C. N. Rensen
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Harro Timmerman
5Food & Biobased Research, Wageningen University & Research, 6708 WG Wageningen, the Netherlands
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Harry J. Wichers
5Food & Biobased Research, Wageningen University & Research, 6708 WG Wageningen, the Netherlands
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Paul A. J. Henricks
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
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Gert Folkerts
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
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Milena Schönke
2Division of Endocrinology, Department of Medicine, Leiden University Medical Center, 2333 BG Leiden, the Netherlands
3Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands
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Saskia Braber
1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, the Netherlands
6Danone Nutricia Research, 3584 CT Utrecht, the Netherlands
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  • For correspondence: [email protected]
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Abstract

Exercise is generally beneficial for health but strenuous exercise can have detrimental effects on the gastrointestinal tract. The combination of ischemia and heat shock during exercise is a crucial contributor to intestinal epithelial damage. Growing evidence points towards an important regulatory role of gut microbes in intestinal homeostasis. Here, we characterize and compare the effects of moderate and vigorous exercise training on intestinal epithelial damage, stress response, inflammatory response, and gut microbiota alterations in mice and investigate the mechanisms underlying exercise-induced intestinal injury. Exercise training for six weeks caused heat stress in the intestine, resulting in the disruption of the intestinal epithelial barrier and local inflammation. This was characterized by increased colonic HSP-70 and HSF-1 protein expression, increased epithelial permeability, decreased colonic expression of tight junction proteins ZO-1 and occludin and intestinal morphological changes. Daily moderate exercise training caused hereby more severe injury than vigorous training on alternating days. Furthermore, exercise training altered the gut microbiota profile. The abundance of Lactobacillaceae was reduced, potentially contributing to the deteriorated intestinal status, while the abundance of short-chain fatty acid-producing Lachnospiraceae was increased, especially following vigorous training. This increase in short-chain fatty acid-producing bacteria following vigorous training possibly counteracted the impairment of the intestinal barrier function. In summary, exercise disrupts the intestinal barrier function, with vigorous exercise training with intermittent rest days being less damaging than daily moderate exercise training.

Competing Interest Statement

The authors have declared no competing interest.

Data Availability Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 14, 2024.
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Exercise training at different intensities induces heat stress, disrupts barrier function and alters microbiota in the gut of mice
Puqiao Lian, Artemiy Kovynev, Lei Wang, Amanda C. M. Pronk, Aswin Verhoeven, Martin Giera, Suzan Thijssen, Borja Martínez Téllez, Sander Kooijman, Patrick C. N. Rensen, Harro Timmerman, Harry J. Wichers, Paul A. J. Henricks, Gert Folkerts, Milena Schönke, Saskia Braber
bioRxiv 2024.07.10.602866; doi: https://doi.org/10.1101/2024.07.10.602866
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Exercise training at different intensities induces heat stress, disrupts barrier function and alters microbiota in the gut of mice
Puqiao Lian, Artemiy Kovynev, Lei Wang, Amanda C. M. Pronk, Aswin Verhoeven, Martin Giera, Suzan Thijssen, Borja Martínez Téllez, Sander Kooijman, Patrick C. N. Rensen, Harro Timmerman, Harry J. Wichers, Paul A. J. Henricks, Gert Folkerts, Milena Schönke, Saskia Braber
bioRxiv 2024.07.10.602866; doi: https://doi.org/10.1101/2024.07.10.602866

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