New Risk Detected in Penicillin for Babies: Made Mouse Pups Turn Mean

Low but clinical doses of penicillin given to mama or nursing baby mice induced persisting changes not only in gut flora and brain inflammation, but in behavior.

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Low-dose penicillin found to change gut bacteria in mice for long term - and behavior in baby mice, also for the long term. That being three weeks in mice.
Low-dose penicillin found to change gut bacteria in mice for long term - and behavior in baby mice, also for the long term. That being three weeks in mice.Credit: Natacha Pisarenko, AP

A groundbreaking study has raised yet more grounds for concern about the merry use of penicillin on babies, and on adults too. An international team of scientists has connected low but clinical doses of penicillin given to pregnant and nursing mice with changes in gut bacteria in all, and persisting changes in behavior in the babies – and not for the better. Other long-term damage was discerned too.

The problems could be mitigated to a degree with probiotics, but only to a degree.

It has long been shown that antibiotic exposure early in life boosts the risk of developing a host of immune and metabolic diseases. Taking antibiotics during pregnancy can boost the probability of asthma in the kids. High doses of antibiotics have been shown to affect behavior and brain neurochemistry in rats, for the long-term. Now the scientists have shown, for the first time, that low (though clinical) doses of penicillin have long-term effects.

Penicillin turned out to alter the gut bacteria in all mice – male, female and kiddies, and not quite as expected. For one thing, the effect was not reversible as had been thought, and for another, it persisted.

"Previous research had indicated that [after antibiotic treatment,] bacterial populations were restored. But our advanced technology, including genetic sequencing, showed that unexpectedly, there was not an absolute return," explains Dr. Omry Koren of the Bar-Ilan University School of Medicine in the Galilee, whose lab handled the gut flora analysis. Three weeks after treatment, the gut flora were still altered.

Moreover, penicillin affected the babies' behavior. Simply, it made the little things meaner (or as the scientists delicately put it, more aggressive), though in parallel, the minute murines exhibited lower levels of anxiety. "We're now checking for that effect in adult mice," Koren added.

The antibiotic also changed the gut bacteria in both sexes, as expected. Less obviously, it boosted the expression of cytokines (signaling molecules) in the frontal cortex of the brain, which has to do with the inflammatory response. And it changed the integrity of the blood-brain barrier. But what does long-term effect mean, in mice?

Three weeks in the life of mice, who live up to about two years, is considered a long time, explains Koren.

Technically, the antibiotics had been administered to the pregnant dams in their last week of pregnancy, the third, and during the nursing period, which is how the babies got the penicillin too. None was given directly to the pups. Then they examined the babies at age three weeks, when nursing ended, and at six weeks, by which time they were near maturity. They found that the problems created by the antibiotics persisted.

"Administering lactobacillus helped alleviate some of the problems," Koren tells Haaretz. "But it did not restore the mice or their biomes [gut bacteria] to their former state."

He also stresses that the results cannot be extrapolated directly to other species, such as our neighbors. But given that our children are dosed with antibiotics practically from birth, and that farm animals are frequently dosed with prophylactic drugs, the findings are worrying.

 “While these studies have been performed in mice, they point to popular increasing concerns about the long-term effects of antibiotics,” stated the study's senior author, Prof. Dr. John Bienenstock of McMaster University, director of the Brain-Body Institute at St. Joseph’s Healthcare Hamilton. “Furthermore,” he says, “our results suggest that a probiotic might be effective in preventing the detrimental effects of the penicillin.”

Mouse-human links are not linear, but both are mammals. 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 same was shown in people in 2015.

“There are almost no babies in North America that haven’t received a course of antibiotics in their first year of life,” Dr. Bienenstock points out. “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.”

We cannot say at this point whether penicillin given to baby humans has the same effect. We can say these results warrant further study on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria, states the team.