Antibiotic use increases risk of severe viral disease in mice: study

CHICAGO, March 28 (Xinhua) -- A study from Washington University School of Medicine in St. Louis showed that mice are more susceptible to severe West Nile disease if they have recently taken antibiotics that change the make-up of their gut bacterial community.

The researchers gave mice a placebo or a cocktail of four antibiotics, vancomycin, neomycin, ampicillin and metronidazole, for two weeks before infecting the mice with West Nile virus. About 80 percent of the mice that received no antibiotics survived the infection, while only 20 percent of the antibiotic-treated mice did.

Subsequent experiments showed that the mice stayed at high risk for more than a week after the antibiotic treatment ended, and just three days of antibiotic treatment was enough to raise the mice's risk of dying from West Nile infection.

To find out whether increased susceptibility to viral infection was linked to changes in gut bacteria, the researchers tested the four antibiotics separately and in combination. Treatment with ampicillin or vancomycin alone made the mice more likely to die of West Nile, while neomycin did not. Metronidazole had no effect alone, but it amplified the effect of ampicillin or vancomycin.

Moreover, different antibiotic treatments led to changes to the bacterial community in the gut that correlated with vulnerability to viral infection.

"Once you put a dent in a microbial community, unexpected things happen," said Larissa Thackray, an assistant professor of medicine of Washington University. "Some groups of bacteria are depleted and different species grow out."

The researchers tested immune cells from mice treated with antibiotics and found that they had low numbers of an important immune cell known as killer T cells. Normally, during an infection T cells that recognize the invading virus multiply to high numbers and play a critical role in controlling the infection. Mice treated with antibiotics generated fewer such T cells.

"It's likely that antibiotic use could increase susceptibility to any virus that is controlled by T cell immunity, and that's many of them," Thackray said.

The weak T cell response is likely a by-product of the changes to the bacterial populations caused by the antibiotics, not a direct effect of the drugs on the immune cells. For one thing, the mice still had trouble fending off viral infection a week or more after they stopped receiving antibiotics. For another, transferring gut bacteria from mice given antibiotics to other antibiotic-treated mice made the recipients even more vulnerable to viral infection, which suggests that something in the bacteria was undermining the mice's immune response.

The study was done in mice and needs to be confirmed in people, whose microbiota normally contains a different collection of bacteria than mice's, the researchers said. Still, the findings suggest that taking antibiotics unnecessarily may be unwise.

The study was published on Tuesday in Cell Reports. Enditem