Low-dose penicillin in early life induces long-term changes in behavior, gut microbes and brain inflammation, study finds
Date: 2017-04-05 Hour: 8:55
In a landmark study, an international group of researchers, including Dr. Omry Koren, of the Bar-Ilan University School of Medicine in the Galilee, has found that providing clinical (low) doses of penicillin to pregnant mice and their offspring results in long-term behavioral changes. These changes include elevated levels of aggression and lower levels of anxiety, accompanied by characteristic neurochemical changes in the brain and an imbalance in their gut microbes. Giving these mice a lactobacillus strain of bacteria helped to prevent these effects.
The study was led by researchers at St. Joseph’s Healthcare Hamilton and McMaster University in Canada. It was published in Nature Communications and was funded by the United States Office of Naval Research.
“In this paper, we report that low-dose penicillin taken late in pregnancy and in early life of mice offspring, changes behavior and the balance of microbes in the gut. While these studies have been performed in mice, they point to popular increasing concerns about the long-term effects of antibiotics,” says the study's senior author, Dr. John Bienenstock, Director of the Brain-Body Institute at St. Joseph’s Healthcare Hamilton and Distinguished Professor at McMaster University.
“Furthermore,” he says, “our results suggest that a probiotic might be effective in preventing the detrimental effects of the penicillin.”
For this study Dr. Koren's lab at the Bar-Ilan University School of Medicine in the Galilee was in charge of characterizing the microbial changes. Using next generation sequencing techniques and bioinformatics, Koren and his team analyzed the microbiomes of mice pups and dams. This study is part of collaboration between the McMaster group and the Bar-Ilan Medical School team, which is funded by a joint research grant by the Canadian Institutes of Health Research, the Israel Science Foundation and the Azrieli Foundation.
Other studies have shown that large doses of broad-spectrum antibiotics in adult animals can affect behavior. But there haven’t been previous studies that have tested the effects of clinical doses of a commonly-used, narrow-spectrum antibiotic such as penicillin on gut bacteria and behavior.
“There are almost no babies in North America that haven’t received a course of antibiotics in their first year of life,” says Dr. Bienenstock. “Antibiotics aren’t only prescribed, but they’re also found in meat and dairy products. If mothers are passing along the effects of these drugs to their as yet unborn children or children after birth, this raises further questions about the long-term effects of our society’s consumption of antibiotics.”
A previous study in 2014 raised similar concerns after finding that giving clinical doses of penicillin to mice in late pregnancy and early life led to a state of vulnerability to dietary induction of obesity.
The research team will follow up their studies by analyzing the effects of penicillin on the offspring, if given only to the pregnant mothers. They also plan on investigating the efficacy of different types of potentially-beneficial bacteria in protecting offspring against the behavioral changes that result from antibiotic usage.