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  3. High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection

High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection

  • Nat Commun. 2023 Jun 30;14(1):3863. doi: 10.1038/s41467-023-39569-0.
Minami Nagai # 1,  Miyu Moriyama # 1,  Chiharu Ishii # 2,  Hirotake Mori 3,  Hikaru Watanabe 4,  Taku Nakahara 4,  Takuji Yamada 4 5,  Dai Ishikawa 4 6 7,  Takamasa Ishikawa 2,  Akiyoshi Hirayama 2,  Ikuo Kimura 8 9,  Akihito Nagahara 6 7,  Toshio Naito 10,  Shinji Fukuda 11 12 13 14 15,  Takeshi Ichinohe 16
Affiliations

Affiliations

  • 1 Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
  • 2 Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
  • 3 Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • 4 Metagen Therapeutics, Inc., Yamagata, Japan.
  • 5 Department of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan.
  • 6 Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
  • 7 Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • 8 Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
  • 9 Department of Applied Biological Science, Graduate School of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.
  • 10 Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan. [email protected].
  • 11 Institute for Advanced Biosciences, Keio University, Yamagata, Japan. [email protected].
  • 12 Metagen Therapeutics, Inc., Yamagata, Japan. [email protected].
  • 13 Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Tokyo, Japan. [email protected].
  • 14 Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, Kanagawa, Japan. [email protected].
  • 15 Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan. [email protected].
  • 16 Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. [email protected].
  • # Contributed equally.
PMID: 37391427 DOI: 10.1038/s41467-023-39569-0
Abstract

Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral Infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including Influenza Virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to Influenza Virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 Infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to Influenza Virus and SARS-CoV-2 in a gut microbiota-dependent manner.

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