Mice given penicillin in pregnancy behave badly
In an effect that scientists are attributing to an intestinal microbial upset, animals treated with penicillin during pregnancy give birth to young with altered brain chemistry, disturbed behaviour and a deranged microbiome.
Penicillin has saved millions of lives since its antibacterial properties were realised in patients in 1942. Now, literally thousands of tonnes of antibiotics like penicillin are used every year around the world. But could there be consequences for a developing baby’s brain if its mother takes antibiotics during her pregnancy?
McMaster University researcher John Bienenstock and his colleagues treated pregnant female mice with therapeutic doses of oral penicillin during the latter phase of their pregnancy. The therapy was continued in the pups after they were born until they were weaned.
Three weeks later the young mice were assessed using a variety of behavioural tests, samples of the intestinal microbes were collected, and brain tissue was examined to look at the integrity of the blood brain barrier and levels of a range of neurochemical and inflammatory markers.
Animals born to antibiotic-treated mothers showed profound and significant changes to their behaviour, becoming much more aggressive and less sociable compared with control animals, the authors report in their paper in Nature Communications. These changes were also correlated with evidence for an altered blood-brain barrier integrity in the antibiotic-exposed animals as well as increased signatures of inflammation in the front part of the brain. Nerve transmitter chemistry was also altered in the treated mice, which showed a shift towards a more aggressive picture.
Predictably, although the intestines themselves showed no signs of disease, the microbiomes of the penicillin-dosed mice were radically different compared with untreated, control animals.
It is this bowel "dysbiosis", or perturbed microbiome, that underpins the changes in behaviour, the McMaster team contend, because when a further group of animals were give doses of "probiotic" bacteria after the penicillin exposure, this helped to partially offset some of the deleterious effects of the penicillin.
The team speculate that the intestinal microbial population secrete factors into the bloodstream, both in the pregnant mother and into the pups once they are born and become colonised with their own bacteria, which are carried to the brain. These factors, which include small carbon-rich fatty acid molecules, influence the development of the brain and structures like the blood brain brain barrier, whose job it is to separate the brain from the chemicals in the bloodstream and thereby preserve the delicate biochemistry of the nervous system.
At the moment it's not clear whether the behavioural effects are permanent in the mice "although the experiments were conducted off antibiotics and some weeks later, suggesting that they might be [permanent]," Bienenstock says. It's also not clear whether the effect is confined purely to pregnancy, or whether early-life exposure is the more dominant effect. "That's what we're looking at now."
The findings are concerning because, in most developed countries, the majority of children by the age of 2 years have already received at least one course of antibiotics. Although Bienenstock cautions that "we don't know yet if this effect in mice translates to humans..."