



Flavonoids, compounds found in many fruits and vegetables, may work with gut microbes to prevent severe flu infections. A flavonoid-rich diet, by itself, may not offer protection, no matter how much black tea or red wine we drink, or how many blueberries we swallow. It appears that the flavonoids need to be metabolized by the right gut microbes, which release flavonoid-derived substances that enter the bloodstream and boost the immune system.

A flavonoid-microbe connection was recently uncovered by scientists based at Washington University School of Medicine in St. Louis. These scientists, led by Thaddeus S. Stappenbeck, M.D., Ph.D., found this connection in mice, which suffer more severe influenza when they receive antibiotics. It has been suggested that antibiotics may worsen influenza in mice by eliminating microbes that produce helpful bioactive metabolites.

The scientists discovered that gut bacteria may metabolize flavonoids to generate a compound called desaminotyrosine (DAT), which triggers interferon (IFN) signaling to boost the immune response. A detailed account of this DAT-mediated immune effect appeared August 4 in the journal Science, in an article entitled “The Microbial Metabolite Desaminotyrosine Protects from Influenza through Type I Interferon.”

“…a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology,” wrote the article’s authors. “A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice.”

This research indicates that the flavonoid–microbe interaction could help stave off severe damage from flu when the interaction occurs prior to infection with the influenza virus. The research might also help explain the wide variation in human responses to influenza infection.

“For years, flavonoids have been thought to have protective properties that help regulate the immune system to fight infections,” said the study’s first author, Ashley L. Steed, M.D., Ph.D.. “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.”

As part of the study, the researchers screened human gut microbes for their ability to metabolize flavonoids. “We were able to identify at least one type of bacteria that uses these dietary compounds to boost interferon, a signaling molecule that aids the immune response,” noted Dr. Stappenbeck. “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.”

“When we gave DAT to mice and then infected them with influenza,” added Dr. Steed, “the mice experienced far less lung damage than mice not treated with DAT.”

Interestingly, although the lungs of DAT-treated mice didn't have as much flu damage, their levels of viral infection were identical to those in mice that didn't get the treatment.

“The infections were basically the same,” Dr. Stappenbeck pointed out. “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.”

That's important because annual flu vaccines aren't always effective at preventing infections.

“But with DAT, it may be possible to keep people from getting quite as sick if they do become infected,” explained Dr. Steed. “This strategy doesn't target the virus. Instead, it targets the immune response to the virus. That could be valuable because there are challenges with therapies and vaccines that target the virus due to changes in the influenza virus that occur over time.”

Next steps include identifying other gut microbes that also may use flavonoids to influence the immune system, as well as exploring ways to boost the levels of those bacteria in people whose intestines aren't adequately colonized with those microbes. As those future studies are planned, the researchers said it might not be a bad idea to drink black tea and eat foods rich in flavonoids before the next flu season begins.



























