Does being treated with antibiotics early in life have an impact in adulthood? That’s the question Sophie Leclercq tried to answer by observing the behaviour of mice exposed in utero to penicillin.
Antibiotics have saved millions of lives. But while they’re a powerful weapon against bacteria and other disease-causing pathogens, they can have other, poorly understood effects, including consequences for the adults whom treated infants become. ‘Several studies have shown a link between antibiotic consumption and subsequent obesity and development of allergies,’ explains Sophie Leclercq, FNRS Research Associate at the Institute of Neuroscience (IONS) and the Louvain Drug Research Institute (LDRI). ‘We also know antibiotics influence the composition of intestinal microbiota, which play a role in the development of immunity. But most of these studies focus solely on adults, very few consider infant exposure.’ Dr Leclercq took up the latter, focusing especially on the behavioural effects in adulthood of prenatal and infant exposure to antibiotics.
Studying mice
To do so, Dr Leclercq studied the effect of antibiotics on adult mice that had been exposed in utero and during the first weeks of life. ‘In the framework of research conducted at McMaster University, in Hamilton, Canada, and funded by the UCL Special Research Fund, we gave mice penicillin – an antibiotic frequently used to treat babies – from the third week of gestation, which corresponds to a woman’s last trimester, through the third week after birth, when nursing ends. Penicillin can pass through the placenta barrier and into mother’s milk, so the baby mice were inevitably exposed to it. Moreover, to be as representative as possible, we administered doses identical to those in routine clinical use for infants.’ When nursing ended, laboratory staff continued feeding the mice. In the sixth week, when the mice entered adulthood, behavioural analysis began.
Less sociable, more aggressive
The results were unequivocal. Mice exposed to penicillin didn’t act the same as unexposed mice. ‘The behaviour of exposed mice differed in three ways. First, they were less sociable. Second, they were less anxious, which isn’t necessarily a good thing for mice, because they become less vigilant and more vulnerable to predators. Third, they became more aggressive with other mice.’
This altered behaviour is associated with an increase in inflammatory cytokines in the frontal cortex, an area of the brain active in many behavioural functions.
Can probiotics limit the effects?
Dr Leclercq also analysed the intestinal microbiota of the exposed mice. ‘They all experienced a change in their microbiota that persisted into adulthood. So we also tested another set of mice by giving them both penicillin and probiotics, specifically lactobacilli, which are bacteria beneficial to and naturally present in the intestine but that antibiotics kill. These mice resumed normal behaviour and had lower levels of inflammatory cytokines in the frontal cortex.’ Could this be a viable way to limit the negative effects of antibiotics?
And humans?
While Dr Leclercq’s findings, which were published in the journal Nature Communication, provide new insight into the long-term effects of infant exposure to antibiotics, it’s premature to draw conclusions relevant to humans. ‘My study concerned only mice, so its findings cannot be applied in any way to humans, but they can serve as a basis for considering excessive use of antibiotics in humans before and immediately after birth, and for developing other studies. For example, the team with whom I work in Canada is trying to determine the most crucial period for exposure: Is it while in the womb or during the first weeks after birth?’
Elise Dubuisson
A glance at Sophie Leclercq's bio
2010-2014 Doctorate in Biomedical Sciences, Institute of Neuroscience (IONS), UCL
2015-2016 Postdoctorate, McMaster University, Hamilton, Canada
Depuis 2016 FNRS Research Associate, Institute of Neurosciences (IONS) and Louvain Drug Research Institute (LDRI)/Metabolism and Nutrition Research
Group (MNUT), UCL