Japanese researchers reveal how you can activate the gut and enhance your immune response during cold, flu, and viral infections.

A recent study by a group of scientists from The University of Tokyo has shed light on the relationship between elevated body temperature and heightened resistance to viral infections.

Previous clinical data points towards a heightened susceptibility of older adults to viral infections, a demographic that also tends to have lower average body temperatures. The influence of elevated body temperature on viral infection resistance, though, remained largely uncharted.

This Japanese research group has now bridged this gap, establishing a connection between increased body temperature and the enhanced antiviral capabilities of gut microorganisms, also known as the “microbiota.” Their work was published in the journal Nature Communications.

For their investigation, the research team utilized mice, exposing them to either cold or hot environments at temperatures of 4°C, 22°C, or 36°C a week prior to infecting them with the influenza virus. Following the virus induction, mice subjected to the cold largely succumbed due to severe hypothermia, whereas the mice exposed to heat exhibited substantial resistance to the infection even at higher virus concentrations.

Dr. Takeshi Ichinohe, from the Division of Viral Infection at The University of Tokyo, Japan, commented: “High-heat-exposed mice raise their basal body temperature above 38°C, allowing them to produce more bile acids in a gut microbiota-dependent manner.”

The team hypothesized that the signaling of deoxycholic acid (DCA) from gut microbiota and its plasma membrane-bound receptor, “Takeda G-protein-coupled receptor 5” (TGR5), enhanced the host’s resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage.

Interestingly, the team found that mice infected with influenza displayed reduced body temperatures nearly four days post-infection, prompting them to huddle for warmth!

The team replicated their findings using SARS-CoV-2 instead of the influenza virus and further verified these results using a Syrian hamster model. Their work demonstrates that a body temperature above 38°C can heighten resistance to influenza virus and SARS-CoV-2 infections. Additionally, this elevated body temperature stimulates crucial gut microbial reactions, subsequently resulting in the production of secondary bile acids. These acids modulate immune responses and provide a protective barrier for the host against viral infections.

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

Following this, the team carried out comprehensive analyses to unravel the exact mechanisms through which gut-metabolite-mediated host resistance to viral infections is triggered in heat-exposed rodents. Additionally, they delineated the role of secondary bile acids and bile acid receptors in protecting against viral infections.

Dr. Ichinohe concluded by saying, “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.”

In essence, the findings from this research suggest that the activation of gut microbiota due to high body temperature elevates the levels of bile acids in the serum and intestine.

This suppresses virus replication and the subsequent inflammatory responses following influenza and SARS-CoV-2 infections.

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