The over-prescription of antibiotics is a major problem in the world today, leading to the dramatic rise of antibiotic-resistant bacteria. New research led by scientists from the Francis Crick Institute in London is suggesting not only are antibiotics ineffective for individuals suffering from influenza, but they can actually worsen the initial viral infection.

The first line of defense against a flu infection is in our lungs. This is where the notorious virus usually begins its infection. The new study describes how the body's early defense strategy involves a process called type I interferon signaling. This primary immune response triggers antiviral genes in cells lining the lung, which subsequently inhibit the speed of a replicating virus.

"Previous studies have focused on immune cells, but we found that the lining cells are more important for the crucial early stages of infection," says Andreas Wack, senior author on the new study. "They are the only place that the virus can multiply, so they are the key battleground in the fight against flu."

Investigating what can modulate this interferon signaling and affect how well our body fights back in the earliest stages of a flu infection, the researchers discovered an antibiotic treatment of just two to four weeks directly inhibits this process.

"It takes around two days for immune cells to mount a response, in which time the virus is multiplying in the lung lining," explains Wack. "Two days after infection, antibiotic-treated mice had five times more virus in their lungs. To face this bigger threat, the immune response is much stronger and more damaging, leading to more severe symptoms and worse outcomes."

At this stage the results of the research suggested that for antibiotics to impair interferon signaling in this way there may be some connection between the gut microbiome and this particular process in the lung. To test this hypothesis, a cohort of mice, previously treated with antibiotics, were then administered a fecal transplant to repopulate their microbiome. After restoring the animal's gut bacteria to its pre-antibiotic status, the researchers detected increases in interferon signaling in the lungs, and improved resistance to flu infections.

Interestingly, this result means that while bacteria certainly seem to modulate the efficacy of interferon signaling in the lung, these bacterial communications unexpectedly originate in the gut. It is unclear exactly how the gut bacteria is communicating with lung tissue to create this effect, and the next step for the researchers is to investigate this unexplained mechanism.

"Taken together, our findings show that gut bacteria help to keep non-immune cells elsewhere in the body prepared for attack," says Andreas. "They are better protected from flu because antiviral genes are already switched on when the virus arrives. So when the virus infects a prepared organism, it has almost lost before the battle starts. By contrast, without gut bacteria, the antiviral genes won't come on until the immune response kicks in. This is sometimes too late as the virus has already multiplied many times, so a massive, damaging immune response is inevitable."

What all this ultimately means is that those on antibiotics may be more susceptible to viral infections. This finding has been suggested by prior animal studies but the mechanism has never been clearly understood until now. Wack notes that the implications of this research span more than just human health, but also encompass the farming industry.

"This could be relevant not only in humans but also livestock animals, as many farms around the world use antibiotics prophylactically," says Wack. "Further research in these environments is urgently needed to see whether this makes them more susceptible to viral infections."

The new study was published in the journal Cell Reports.