Lactobacillus rescues postnatal neurobehavioral and microglial dysfunction in a model of maternal microbiome dysbiosis

Brain Behav Immun. 2019 Oct;81:617-629. doi: 10.1016/j.bbi.2019.07.025. Epub 2019 Jul 24.

Abstract

Increasing reports of pregnancy events leading to maternal microbiome dysbiosis (MMD) show strong correlates with atypical neurodevelopmental outcomes. However, the mechanism(s) driving microbiome-mediated behavioral dysfunction in offspring remain understudied. Here, we demonstrate the presence of a novel gut commensal bacterium strain, Lactobacillus murinus HU-1, was sufficient to rescue behavioral deficits and brain region-specific microglial activationobserved in MMD-reared murine offspring. We furtheridentified a postnatal window of susceptibility that could prevent social impairments with timed maternal administration of the symbiotic bacterium. Moreover, MMD increased expression of microglial senescence genes, Trp53 and Il1β, and Cx3cr1 protein in the prefrontal cortex, which correlated with dysfunctional modeling of synapses and accompanied dysbiosis-induced microglial activation. MMD male offspring harboring Lactobacillus murinus HU-1 or lacking Cx3cr1 showed amelioration of these effects. The current study describes a new avenue of influence by which maternally transferred Lactobacillus drives proper development of social behavior in the offspring through microglia-specific regulation of Cx3cr1 signaling.

Keywords: Autism spectrum disorders; Cx3cr1; Gut bacteria; Microbiota; Neurodevelopment; Senescence; Social behavior; Trp53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / microbiology
  • CX3C Chemokine Receptor 1 / metabolism
  • Dysbiosis / microbiology
  • Female
  • Gastrointestinal Microbiome / physiology
  • Interleukin-1beta / metabolism
  • Lactobacillus / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / physiology*
  • Microglia / physiology
  • Neurodevelopmental Disorders / microbiology*
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / microbiology
  • Pregnancy
  • Social Behavior
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Interleukin-1beta
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53