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Updated: Apr 28, 2026

A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Abnormal intestinal microbial colonization in prenatally stressed offspring is related to lung and intestinal
Audrey F Duff1,2, Michael T Bailey1,2,3
1Center for Microbe and Immunity Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.
Insights
Prenatal stress (PNS) alters the early-life microbiome, impacting offspring immune development. These changes correlate with increased respiratory infections and are dependent on the MyD88 pathway.
Area of Science:
- Immunology
- Microbiology
- Developmental Biology
Background:
- Prenatal stress (PNS) negatively affects child health, increasing susceptibility to early-life infections like respiratory infections.
- Maternal microbiome alterations during pregnancy due to stress are a key factor linking in utero stress to abnormal offspring development and microbial colonization.
Purpose of the Study:
- To investigate the relationship between early-life intestinal microbial perturbations and intestinal/lung cytokine gene expression in a mouse model of PNS.
- To characterize basal cytokine differences in relation to intestinal microbial composition in PNS-exposed offspring.
Main Methods:
- A mouse model of prenatal stress (PNS) was utilized.
- Intestinal microbiome composition, diversity, and differential abundance were assessed.
- Intestinal and lung tissue gene expression, specifically focusing on cytokines, was analyzed over the first five weeks of life.
- Experiments included MyD88 knockout mice to assess pathway dependency.
Main Results:
- PNS offspring showed significant alterations in microbiome diversity and composition.
- Increased interferon and proinflammatory cytokine gene signatures were observed in the ileum and lung of PNS offspring.
- PNS-associated microbiome changes correlated with ileal and lung gene expression.
- MyD88 knockout offspring did not exhibit PNS-associated cytokine differences.
Conclusions:
- PNS-induced early-life microbiome changes are linked to immune development in the gut and lungs.
- Microbe-immune interactions influenced by PNS are dependent on the MyD88 signaling pathway.
Introduction:
Prenatal stress (PNS) is associated with deleterious effects on childhood health and wellbeing. Among these consequential health repercussions, PNS-exposed children are at increased risk for acquiring early-life infections, with respiratory infections frequently reported. Stress-induced perturbations in the maternal microbiome during pregnancy represent a key link between stress in utero and aberrant offspring development and can drive abnormal pioneer colonization of offspring microbiomes.
Methods:
Using a mouse model of PNS, we aimed to understand the extent to which these early-life intestinal microbial perturbations are related to intestinal and lung cytokine gene expression. The intestinal microbiome alongside intestinal and lung tissue gene expression were assessed over the first five weeks of life in PNS-exposed offspring to characterize basal cytokine differences in relation to intestinal microbial composition.
Results:
In addition to significant changes in microbiome diversity and differential abundance, PNS offspring exhibited significant differences in ileal and lung cytokines characterized by overall increased interferon and proinflammatory gene signatures. PNS-associated microbiome changes also correlated to gene expression in both the ileum and lung. Finally, PNS-associated cytokine differences were not observed in MyD88-/- offspring which lack the ability to initiate inflammatory responses through microbially-stimulated toll-like receptor signaling.
Conclusion:
These findings suggest that PNS-mediated changes in the early-life microbiome are linked to respiratory and ileal immune development and the microbe-immune interactions are MyD88 pathway-dependent.
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