A substance produced in the gut as a result of eating flavonoids appears to give protection against the severity of flu in mice, found scientists from Washington University School of Medicine, St. Louis.
"The metabolite is called desaminotyrosine, otherwise known as DAT," commented first author, Dr. Ashley Steed.
"When we gave DAT to mice and then infected them with influenza, the mice experienced far less lung damage than mice not treated with DAT," she added
Eating flavonoids only works however, if you have the right type of gut bacteria. By screening the human microbiome, the researchers found that DAT was produced through flavonoid metabolism by a specific species of bacteria Clostridium orbiscindens.
"It's not only having a diet rich in flavonoids, our results show you also need the right microbes in the intestine to use those flavonoids to control the immune response," said senior author, Professor Thaddeus Stappenbeck.
DAT reduces infection severity
Although DAT did not prevent flu in mice, the flavonoid metabolite reduced the severity of infections by altering their immune response. Even though DAT-treated mice had identical levels of viral infection to non-treated animals, the former group showed lower levels of lung damage.
"The infections were basically the same," Stappenbeck said. "The microbes and DAT didn't prevent the flu infection itself; the mice still had the virus. But the DAT kept the immune system from harming the lung tissue."
The findings might eventually enable strategies for protecting vulnerable people against harmful complications of influenza such as pneumonia, suggested the researchers.
"With DAT, it may be possible to keep people from getting quite as sick if they do become infected," Steed said. "This strategy doesn't target the virus. Instead, it targets the immune response to the virus.”
Mechanism
The scientists established that DAT exerts its effect by boosting the type-1 interferon signalling pathway. (Interferons are a group of proteins that help regulate the activity of the immune system).
"We were able to identify at least one type of bacteria that uses these dietary compounds to boost interferon, a signalling molecule that aids the immune response. This prevented influenza-related lung damage in the mice. It is this kind of damage that often causes significant complications such as pneumonia in people."
Further work will include identifying other species of gut bacteria that may also use flavonoids to boost the immune response and exploring ways of colonising the intestines of people with inadequate numbers of these protective microbes.
"For years, flavonoids have been thought to have protective properties that help regulate the immune system to fight infections," concluded Steed.
"Flavonoids are common in our diets, so an important implication of our study is that it's possible flavonoids work with gut microbes to protect us from flu and other viral infections. Obviously, we need to learn more, but our results are intriguing."
Source: Science
Volume 357, Issue 6350. Pages: 498-502 DOI: 10.1126/science.aam5336
“The microbial metabolite desaminotyrosine protects from influenza through type I interferon”
Authors: Ashley L. Steed, Thaddeus S. Stappenbeck, et al