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

The ambient environmental temperature changes the extent or severity of a virus infection. Here the authors show that influenza and SARS-CoV-2 infection at higher temperatures promotes gut microbiota derived deoxycholic acid signalling which increases host resistance to infection. 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 & DEG;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 & DEG;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.

Automated summary

The ambient environmental temperature plays a role in the severity of a virus infection. Research shows that infection with influenza and SARS-CoV-2 at higher temperatures promotes gut microbiota derived deoxycholic acid signaling, which increases the host's resistance to infection.