Unique maternal immune and functional microbial profiles during prenatal stress

Area of Science:

• Immunology
• Neuroscience
• Microbiome Research

Background:

• Maternal stress during pregnancy is linked to adverse offspring neurodevelopmental and mental health outcomes.
• Prenatal stress may induce fetal neuroinflammation by disrupting intrauterine immune homeostasis, but its origins are unclear.
• Understanding these mechanisms is crucial for mitigating long-term health issues in offspring.

Purpose of the Study:

• To investigate divergent immune and microbial metagenome profiles in stressed pregnant mice.
• To identify triggers for detrimental inflammatory signaling at the maternal-fetal interface.
• To elucidate the complex signaling patterns underlying prenatal stress effects on fetal development.

Main Methods:

• Analysis of maternal glucocorticoid circuit activation and systemic immune markers.
• Assessment of placental mononuclear leukocyte density and maternal blood leukocyte phenotypes (monocytosis, M1 shift).
• Genome-resolved microbial metagenomic analysis of maternal gut microbiome, focusing on gene, strain, and pathway alterations.

Main Results:

• Stress induced maternal glucocorticoid activation and systemic immunosuppression.
• Placental leukocyte density decreased, while maternal blood showed monocytosis and M1 phenotypic shifts.
• Microbial metagenomics revealed reduced pro-inflammatory genes, strains, and pathways, with specific disruption of *Parasutterella excrementihominis*.

Conclusions:

• Prenatal stress perturbs maternal immune and microbial regulation, potentially disrupting immune equilibrium at the maternal-fetal interface.
• The observed immune and microbial dysregulation, particularly involving *Parasutterella excrementihominis*, contributes to inflammatory and metabolic issues.
• The absence of overt maternal inflammation suggests nuanced signaling pathways mediate prenatal stress effects on fetal outcomes.