Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring

Area of Science:

• Neuroscience
• Immunology
• Microbiology

Background:

• Maternal immune activation (MIA) is linked to neurodevelopmental disorders in offspring.
• Interleukin-17a (IL-17a) from T helper 17 (T_H17) cells mediates MIA-associated abnormalities in rodents.
• The role of other maternal factors and mechanisms of MIA-induced T cell activation remain unclear.

Purpose of the Study:

• To investigate the role of maternal intestinal bacteria in MIA-associated neurodevelopmental abnormalities.
• To elucidate the mechanisms by which MIA leads to T_H17 cell activation and IL-17a production.

Main Methods:

• Colonization of pregnant mice with specific gut bacteria (segmented filamentous bacteria or human commensal bacteria).
• Assessment of offspring for behavioral and cortical abnormalities.
• Analysis of cytokine secretion (IL-1β, IL-23, IL-6) by maternal small intestine dendritic cells.

Main Results:

• Maternal colonization with T_H17-inducing bacteria increased the incidence of MIA-associated offspring abnormalities.
• MIA induced IL-17a production in offspring.
• Pregnant mice exposed to MIA showed increased secretion of IL-1β, IL-23, and IL-6 by small intestine dendritic cells, stimulating T_H17 cell differentiation.

Conclusions:

• Maternal intestinal bacteria that induce T_H17 cell differentiation are essential for MIA-associated neurodevelopmental phenotypes in offspring.
• Defined gut commensal bacteria may increase the risk of neurodevelopmental disorders in offspring of mothers with immune activation.