A new study with mice shows that antibiotic overuse can increase the severity of West Nile virus infections because of its negative impact on the gut microbiome. While the connection between antibiotics, the immune system, and the microbiome hasn’t been tested like this in humans or with other viruses, the study provides interesting findings that highlight the importance of the gut microbiome.
Like other viral infections, a West Nile virus infection sometimes causes no symptoms, but it sometimes causes dangerous brain infections. The genetics of either humans or the virus can’t fully explain why the virus has different impacts on people. Scientists from the Washington University School of Medicine theorized that the difference may be a result of diversity in microbiomes, which affects immune activity.
"If someone is sick with a bacterial infection, they absolutely should take antibiotics. But it is important to remember that there may be collateral effects,” explained senior author Michael S. Diamond, MD, PhD. “You might be affecting your immune response to certain viral infections."
In their study, researchers found that mice are more susceptible to severe West Nile virus infections if they’ve recently received antibiotics that alter the gut microbiome. The problem is that antibiotics sometimes kill more bacteria than the particular species they are intended to kill, and that includes beneficial bacteria from the gut microbiome. The immune system interacts with the gut microbiome, so changes in the microbiome causes a disturbance in the immune system, a disturbance which is apparently particularly evident in West Nile virus infection.
Mice given either a placebo or a combination of four antibiotics: vancomycin, neomycin, ampicillin, and metronidazole. Mice were given treatment for two weeks before they were infected with West Nile virus, but researchers ultimately found that it only took three days of antibiotic treatment to increase their risk of death from infection.
80 percent of the mice who received the placebo survived, and only 20 percent of the mice who got antibiotics survived. And for those receiving antibiotics who made it through, they remained at a high risk of death for more than a week after taking the drugs.
Researchers ultimately found that different combinations of antibiotics had varying effects on the risk of death from West Nile virus and different effects on the gut microbiome. For example, immune cells called killer T cells from mice given antibiotics were present in abnormally low levels, an indirect result of antibiotic use, with changes in the microbiome being the key problem.
“Increased susceptibility may be due to both the loss of a normal signal that promotes good immunity and the gain of an inhibitory signal,” explained first author Larissa Thackray, PhD.
Diamond, Thackray, and others still need to confirm the connection between the immune system, antibiotics, and the gut microbiome in humans. For now, the study’s findings support the idea that overuse of antibiotics can have dangerous consequences.
The present study was published in the journal Cell Reports.