Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota

Brain Behav Immun. 2020 Feb;84:154-163. doi: 10.1016/j.bbi.2019.11.020. Epub 2019 Nov 27.

Abstract

Growing evidence suggests that environmental disruptors of maternal microbes may have significant detrimental consequences for the developing fetus. Antibiotic exposure during early life can have long-term effects on neurodevelopment in mice and humans. Here we explore whether exposure to low-dose penicillin during only the last week of gestation in mice has long-term effects on offspring behaviour, brain, immune function, and gut microbiota. We found that this treatment had sex-specific effects in the adult mouse offspring. Female, but not male, mice demonstrated decreased anxiety-like behaviours, while male, but not female, mice had abnormal social behaviours which correlated with altered brain expression of AVPR1A, AVPR1B, and OXTR, and decreases in the balance of splenic FOXP3+ regulatory T cells. Prenatal penicillin exposure also led to distinct microbiota compositions that clustered differently by sex. These data suggest that exposure of pregnant mice to even a low dose of penicillin through only the last week before birth is nonetheless sufficient to induce long-term sex-specific developmental changes in both male and female offspring.

Keywords: Antibiotics; Behaviour; Brain; Dysbiosis; Immune regulation; Microbiota; Microbiota-gut-brain axis; Nervous system; Neurodevelopment; Neurotoxicity.

Publication types

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

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Immunity / drug effects*
  • Male
  • Mice
  • Penicillins / administration & dosage*
  • Penicillins / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / immunology*
  • Prenatal Exposure Delayed Effects / microbiology
  • Prenatal Exposure Delayed Effects / physiopathology*
  • Sex Characteristics*
  • Social Behavior*

Substances

  • Penicillins

Grant support