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Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice

Jing Lu1, Lei Lu1, Yueyue Yu1

  • 1The University of Chicago, Pritzker School of Medicine, Department of Pediatrics, Chicago, IL, 60637, USA.

Scientific Reports
|April 5, 2018
PubMed

Insights

The gut microbiome influences preterm infant growth and brain development. Specific infant microbiotas affect neuronal development and neuroinflammation, impacting neurodevelopmental outcomes.

Area of Science:

  • Microbiology
  • Neuroscience
  • Developmental Biology

Background:

  • Poor growth in Neonatal Intensive Care Units (NICU) is linked to adverse neurodevelopmental outcomes in preterm infants.
  • The gut microbiome is a critical, modifiable factor influencing host development.
  • Mechanisms linking infant growth and brain development remain unclear.

Purpose of the Study:

  • To investigate the hypothesis that the gut microbiome influences both growth phenotype and brain development in preterm infants.
  • To examine the impact of specific preterm infant microbiotas on postnatal brain development using a mouse model.

Main Methods:

  • Utilized a germ-free mouse transfaunation model.
  • Introduced microbiotas associated with high-growth and low-growth phenotypes from preterm infants.
  • Assessed neuronal markers (NeuN, neurofilament-L), myelination (MBP), neuroinflammation (Nos1), and the IGF-1 pathway.

Main Results:

  • Microbiota inducing low growth showed decreased neuronal and myelination markers compared to high-growth microbiota.
  • Low-growth microbiota was associated with increased neuroinflammation (Nos1).
  • Alterations in the IGF-1 pathway were observed, including decreased circulating and brain IGF-1 and altered IGFBP3 expression.

Conclusions:

  • Growth-associated gut microbiota can significantly influence early neuron and oligodendrocyte development in preterm infants.
  • The effects on brain development may be mediated by neuroinflammation and the insulin-like growth factor 1 (IGF-1) pathway.
  • Targeting the microbiome presents a potential strategy to improve neurodevelopmental outcomes in preterm infants.

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