Gut bugs to lungs' rescue

Commensal microbes in the gut may help combat the flu virus in the lungs

By | March 14, 2011

The commensal bacteria of the gut, essential for digestion and the overall well-being of the intestines, also play a critical role in mounting an immune response to the flu virus in the lungs.
linkurl:Wikimedia Commons, Patrick J. Lynch;
The results, linkurl:published today; (March 14) in the Proceedings of the National Academy of Sciences, suggest that antibiotic use could impair a person's ability to combat the seasonal virus. "This work is in line with an emergence of research about how much commensal [bacteria] affect not only the metabolism of a host, but also the immunity," said linkurl:Yasmine Belkaid,; chief of the Mucosal Immunology Section at the National Institute of Allergy and Infectious Diseases. "It's a very informative study." A team at the Yale University School of Medicine treated mice with combinations of antibiotics, then challenged them with the influenza virus. The animals exhibited a significantly impaired immune response, including reduced levels of T cells and influenza-specific antibodies, and high amounts of virus in the lungs. "This was a finding that we didn't expect," said senior author linkurl:Akiko Iwasaki,; an immunologist at Yale. The study is the first to demonstrate that commensal bacteria provide a signal to the body that prepares distal organs, in this case the lungs, to mount an immune response, she said. "It seems that the commensal bacteria in the gut are providing a crucial signal throughout the body that prepares the body for fighting infection," said Iwasaki. The specific mechanism by which the microbes help mount an immune response is unclear, though the researchers suspect a role for the secretion of cytokines, which activate immune cells. In the antibiotic treated mice, these cytokines were not being synthesized in the lungs, as they were in untreated mice. It's possible, they say, that the microbes activate Toll-like receptors in the gut -- important receptors for immunity -- and lead to the release of cytokines such as IL-1beta, throughout the body. "We think it's a distal control," said Iwasaki. "Something that's happening in the intestine is affecting the responses in other places. And it's probably not only restricted to lungs." Recent studies have linked gut microbe compositions to linkurl:brain development; and conditions like diabetes and obesity. The team also has yet to determine which microbes support immune activation in the lungs, though it is most likely a neomycin-sensitive bacteria, as treating with the antibiotic neomycin alone had the same effects as an antibiotic cocktail. The results suggest that long-term use of antibiotics could hamper an individual's ability to fight influenza, said Iwasaki, perhaps even impair the effect of a vaccine. "This is something people need to consider when they think about utilizing antibiotic treatment," agreed Belkaid. But on a positive note, the authors also suggest that probiotic treatments, such as yogurt, may help stimulate the immune system during flu season. Ichinohe, T., et al., "Microbiota regulates immune defense against respiratory tract influenza A virus infection," PNAS, doi:10.1073/pnas.1019378108.
**__Related stories and F1000 evaluations:__***linkurl:Gut microbiota modulate brain development;
[15th February 2011] *linkurl:Opening a Can of Worms;
[1st February 2011] *linkurl: New gut bacteria regulate immunity;
[23rd December 2010]


Avatar of: Mike Waldrep

Mike Waldrep

Posts: 155

March 15, 2011

Avatar of: Yuval Sagiv

Yuval Sagiv

Posts: 1

March 21, 2011

did they test for natural airway flora? one can assume that elimination of antibiotics-sensitive bacteria in the airway will result this effect (as long as there is some systemic effect of the antibiotics)
Avatar of: John Dos Santos

John Dos Santos

Posts: 9

March 22, 2011

Neomycin is not absorbed in the GI tract, and it is toxic when given IV. Therefore neomycin only acts on gut bacteria since it could only be given orally.\n\n"treating with the antibiotic neomycin alone had the same effects as an antibiotic cocktail."\n\nThis statement suggests that it is indeed gut bacteria that is responsible for the bulk, if not all, of the immune modulating effect in mice.\n\n\nSeniors are at increased risk of complications from influenza. This is an important observation to keep in mind as seniors commonly receive antibiotics for chest infections during the flu season.

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