Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

Sophie Leclercq,Emmanuel Cambier,John Bienenstock,Firoz M Mian,Paul Forsythe,Andrew M Stanisz,Hila Ben-Amram,Laure B Bindels,Omry Koren

doi:10.1038/ncomms15062

Abstract

There is increasing concern about potential long-term effects of antibiotics on children’s health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.

Highlights

There is increasing concern about potential long-term effects of antibiotics on children’s health
We tested whether concurrent supplementation with Lactobacillus rhamnosus JB-1 (JB-1) may counteract the biological and behavioural changes induced by early life AB
We find that AB-treated mice have lasting changes in gut microbiota, modified blood– brain barrier (BBB) integrity in the hippocampus, increased levels of cytokines in the frontal cortex and behavioural alterations including decreased anxiety-like behaviour and increased aggression in males as well as reduced social behaviour in males and females

Summary

Introduction

There is increasing concern about potential long-term effects of antibiotics on children’s health. We find that AB-treated mice have lasting changes in gut microbiota, modified BBB integrity in the hippocampus, increased levels of cytokines in the frontal cortex and behavioural alterations including decreased anxiety-like behaviour and increased aggression in males as well as reduced social behaviour in males and females.

Results

Conclusion