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A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
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Lactobacillus rescues postnatal neurobehavioral and microglial dysfunction in a model of maternal microbiome

Yeonwoo Lebovitz1, Elizabeth A Kowalski2, Xia Wang2

  • 1Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA 24061, USA.

Brain, Behavior, and Immunity
|July 28, 2019
PubMed

Insights

Maternal microbiome dysbiosis (MMD) impacts offspring neurodevelopment. Supplementing Lactobacillus murinus HU-1 during a critical window can prevent social deficits by regulating microglial Cx3cr1 signaling.

Area of Science:

  • Neuroscience
  • Microbiology
  • Developmental Biology

Background:

  • Maternal microbiome dysbiosis (MMD) is increasingly linked to atypical neurodevelopmental outcomes in offspring.
  • Mechanisms underlying microbiome-mediated behavioral dysfunction in offspring are not well understood.

Purpose of the Study:

  • To investigate the role of Lactobacillus murinus HU-1 in rescuing MMD-induced behavioral deficits.
  • To identify critical developmental windows for intervention and explore molecular pathways involved.

Main Methods:

  • Utilized a murine model of MMD and assessed offspring behavior and neuroinflammation.
  • Administered Lactobacillus murinus HU-1 during specific postnatal periods.
  • Analyzed microglial gene expression (Trp53, Il1β) and protein levels (Cx3cr1) in the prefrontal cortex.

Main Results:

  • Lactobacillus murinus HU-1 administration rescued behavioral deficits and normalized microglial activation in MMD offspring.
  • A specific postnatal window was identified for effective intervention.
  • MMD increased microglial senescence genes and Cx3cr1 protein, correlating with synaptic dysfunction.

Conclusions:

  • Maternally transferred Lactobacillus, specifically L. murinus HU-1, can restore proper social behavior development.
  • Microglia-specific regulation of Cx3cr1 signaling is a key pathway influenced by maternal microbes.
  • Targeted probiotic intervention offers a potential strategy for mitigating MMD-associated neurodevelopmental issues.
Keywords:
Autism spectrum disordersCx3cr1Gut bacteriaMicrobiotaNeurodevelopmentSenescenceSocial behaviorTrp53

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