According to research published September 5, 2019 in the journal Cell, scientists discovered that a course of antibiotics may cut the effectiveness of the flu vaccine by killing off gut microbes that appear to play an important role in keeping the immune system healthy. RELATED: Cold and Flu 101 “This study really further demonstrates the relationship between our gut microbiome and immune system,” says Alan Embry, PhD, the chief of the respiratory diseases branch in the division of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases. NIAID is part of the National Institutes of Health (NIH), which funded this research.

A Closer Look at How Antibiotics Influence Immune Response

“This research shows that disrupting the microbiome in some individuals had a measurable effect on vaccine responses,” Dr. Embry says, “but much more work is needed to understand if and how the normal use of antibiotics will affect influenza vaccine response.” The research team, led by Bali Pulendran, PhD, a professor of pathology and of microbiology and immunology at the Stanford University School of Medicine, examined 22 volunteers during the 2014–15 flu season and 11 participants during the 2015–16 flu season. They ranged in age from 18 to 45. Half the individuals in each group received a five-day broad-spectrum regimen of antibiotics before getting their flu shot. The antibiotic mix consisted of neomycin, vancomycin, and metronidazole. Vancomycin and metronidazole are commonly prescribed for gastrointestinal infections such as Clostridium difficile (or C. diff). Neomycin is an antibiotic used not only to reduce the risk of infection during intestinal surgery but also to treat skin infections.

Inflammation Rises as Gut Bacteria Go Down

The researchers measured immune response to the flu shot and diversity and abundance of gut microbes by analyzing stool and blood serum samples taken at various points during a one-year follow-up period. They found that people taking the antibiotics experienced a 10,000-fold drop in their gut bacteria population — a loss that lasted up to a year after they took the drugs. These participants also displayed signs of systemic inflammation that mirrored a pro-inflammatory state seen among people age 65 and older who have gotten the flu shot. Scientists speculate that the inflammation may be connected to how the microbiome regulates bile acid.

Connection Between Vaccine Response and Preexisting Immunity

The response to the flu vaccine differed between the two groups. All of the first 22 volunteers from 2014–15 turned out to have high levels of flu antibodies to begin with. So, whether they took antibiotics or not, they had a preexisting immunity to that season’s flu virus strain. In the 2015–16 group, however, all selected participants had low levels of flu antibodies at the start and low immunity. None had received a flu vaccination in the three years prior. After getting the flu shot, those who also took the antibiotics had a significant drop in antibodies that would protect them from the H1N1 virus. Study authors suggest that if these individuals were exposed to this H1N1 virus after vaccination, they would most likely be less protected against getting the flu than people who had not received antibiotics. “Interestingly, the effect on the vaccine response was seen only in people with low levels of preexisting immunity to this vaccine,” says Embry. “It’s important to note that the antibiotic treatment did not appear to significantly impact the immune responses in those who had higher levels of preexisting immunity to influenza.”

NIH Is Committed to More Flu Vaccine Research

William Schaffner, MD, an infectious disease specialist and a professor of preventive medicine and health policy at the Vanderbilt University School of Medicine in Nashville, Tennessee, sees the study results as building on evidence indicating that the microbiome — the trillions of microbes that live in the gastrointestinal tract — has a pervasive effect on our health. “Taking antibiotics clearly had a measurable reduction in the immune response, but we don’t know whether it’s clinically significant yet,” says Dr. Schaffner, who was not involved in the study. “It could be that if you’re taking antibiotics it might not be a good time to get a flu vaccine, but we’re not quite there yet in terms of research.” He also points out that the antibiotic combination used in this investigation was not one seen in common practice. “This antibiotic cocktail is a very unusual mix of ingredients,” says Schaffner. “It seems specifically designed to kill off as many gut bacteria as possible.” For future research, Schaffner would like to see a larger study population and an antibiotic combination used in standard treatment. “Significantly more work needs to be done to truly understand the real impact of the microbiome on influenza,” says Embry. Embry adds that the NIH will continue to support research exploring factors that may improve human immune response to influenza vaccines.

“This study is early in nature,” says Embry. “Right now I’m not sure that there is anything to definitively say that you should wait to get the influenza vaccine if you’ve had antibiotic treatments. At this stage, I’d say that it is important to get the flu vaccine when it’s recommended to be administered for the upcoming season.” The Centers for Disease Control and Prevention (CDC) still recommends that everyone age six months and older get an annual influenza vaccination. The flu vaccine reduces the risk of flu illness by between 40 and 60 percent among the overall population during seasons when most circulating flu viruses are well-matched to the flu vaccine, according to the CDC.