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

Nat Commun. 2017 Apr 4;8:15062. 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / toxicity
  • Anxiety / chemically induced
  • Anxiety / physiopathology
  • Anxiety / prevention & control
  • Cytokines / metabolism*
  • Female
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism*
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Lactobacillus / physiology
  • Male
  • Mice, Inbred C57BL
  • Penicillin V / administration & dosage*
  • Penicillin V / toxicity
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Prenatal Exposure Delayed Effects / prevention & control
  • Probiotics / administration & dosage
  • Social Behavior*

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Penicillin V