Editors' ChoiceMICROBIOTA

The antisocial side of antibiotics

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Science Translational Medicine  26 Apr 2017:
Vol. 9, Issue 387, eaan2786
DOI: 10.1126/scitranslmed.aan2786

Abstract

Perinatal exposure to penicillin may result in long-lasting gut and behavioral changes.

The discovery of antibiotics marks one of the most important achievements in the history of medicine. It is probably not required to reiterate here the countless deaths antibiotics have prevented and are still preventing. However, misuse and overuse of antimicrobial drugs have also led to unfortunate consequences. Thus, identifying ways to prevent unwanted outcomes of antibacterial-based therapies remains an important research theme.

Early life exposure to antibiotics has been associated with increased risk of diverse conditions, including poor cognitive outcomes and lack of intuitive social abilities. Similarly, emerging literature suggests a link between disruption of the gut microbiota and mental health issues. Recently, Leclercq and colleagues have explored the effects of early life exposure to low-dose, clinically appropriate, penicillin on gut microbiome and behavior in mice.

The authors treated pregnant dams with penicillin starting one week before delivery up until the weaning of the pups. Since ingested penicillin is found in the fetal circulation and in breast milk, the pups were effectively exposed to the antibiotic prenatally and postnatally. As expected, exposure to penicillin led to changes in the gut microbiome composition of the treated dams and their offspring. For example, antibiotic-treated animals presented with increased levels of Proteobacteria, gram-negative bacteria, which can activate substantial immune reactions in the host. Importantly, the dysbiosis was not limited to the period of penicillin intake but it was protracted for several weeks after antibiotic administration was terminated.

To understand whether exposure to penicillin, and the associated dysbiosis, could lead to long-lasting consequences on cognitive functions, the authors tested antibiotic-exposed mice for behavioral changes. Mice exposed to low doses of antibiotic perinatally were less anxious, more aggressive, and less prone to engage in social interactions. The behavioral alterations were accompanied by changes in expression of genes previously linked to aggression and blood-brain barrier integrity, but no signs of systemic inflammation were detected. Most importantly, the above-mentioned alterations were observed in antibiotic-exposed mice tested several weeks after the treatment was ceased. However, the authors also show that supplementation with Lactobacillus rhamnosus during the treatment supports the gut microbiome and prevents behavioral alterations.

In conclusion, although performed solely on a mouse model, the study by Leclercq and colleagues provides some evidence that perinatal exposure to low doses of penicillin has long-lasting effects on gut microbiota and behavior. The authors also suggest that associating antibiotic treatment with supplementation of beneficial bacteria can be sufficient to counteract the deleterious effects of penicillin exposure.

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