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"Influenza Virus" by NIAID. (CREDIT Minami Nagai, Miyu Moriyama, Chiharu Ishii, Hirotake Mori, Hikaru Watanabe, Taku Nakahara, Takuji Yamada, Dai Ishikawa, Takamasa Ishikawa, Akiyoshi Hirayama, Ikuo Kimura, Akihito Nagahara, Toshio Naito, Shinji Fukuda, Takeshi Ichinohe)

TOKYO, Japan — Researchers in Japan have uncovered a critical connection between higher body temperatures and enhanced resistance against viral infections. The team from the University of Tokyo found that elderly individuals, who often have lower average body temperatures, are more susceptible to viral infections.

The study sheds light on the critical role the gut microbiota plays in fortifying the body against viruses like influenza and SARS-CoV-2 when body temperature exceeds 38 degrees Celcius (100 degrees Fahrenheit). During their experiments, the research team exposed mice to different temperature conditions before inducing them with the influenza virus.

“High-heat-exposed mice raise their basal body temperature above 38 degrees Celcius, allowing them to produce more bile acids in a gut microbiota-dependent manner,” says Dr. Takeshi Ichinohe, from the Division of Viral Infection at the University of Tokyo, in a media release.

Mice with higher body temperatures due to heat exposure showed remarkable resistance to increasing doses of the virus, in sharp contrast to the cold-exposed counterparts who faced severe outcomes. The team proposed that a component from the gut microbiota, deoxycholic acid (DCA), along with its receptor Takeda G-protein-coupled receptor 5 (TGR5), played a pivotal role in bolstering resistance to the influenza virus. This resistance was attributed to a reduction in virus replication and prevention of tissue damage.

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Interestingly, the team observed a behavior where infected mice huddled together for warmth, and their findings remained consistent even when the influenza virus was replaced with SARS-CoV-2. They validated these results using Syrian hamsters, determining that elevated body temperatures could indeed enhance resistance to these viral infections. Furthermore, the research highlighted the role of certain bile acids in the immune response against these viruses.

“The DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection,” explains Dr. Ichinohe. “Moreover, 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.”

The study suggests that high body temperatures activate gut microbiota, leading to increased bile acid levels, which in turn suppress virus replication and the inflammatory responses often seen with influenza and SARS-CoV-2 infections.

“Our finding that reduction of certain bile acids in the plasma of patients with moderate I/II COVID-19 may provide insight into the variability in clinical disease manifestation in humans and enable approaches for mitigating COVID-19 outcomes,” concludes Dr. Ichinohe.

The study is published in the journal Nature Communications.

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