Both genetic and environmental factors contribute to the development of autism spectrum disorder (ASD). Maternal inflammation during pregnancy is known to increase the risk of ASD and other neuropsychiatric disorders in offspring, but the mechanism by which this occurs is still poorly understood. For example, it is currently unknown whether the gut microbiota composition in the mother during pregnancy influences the inflammation associated with ASD or if microbe-regulated immune responses are translated into effectors of ASD phenotypes in the offspring.

Using a combination of mice subjected to maternal immune activation (MIA) and genetically modified mice targeting a distinct subset of immune cells, Jun Huh, Dan Littman and their colleagues recently identified Th17 cells in pregnant females as critical mediators of maternal inflammation-induced ASD phenotypes in offspring¹. The Littman laboratory had previously determined that segmented filamentous bacterium, a commensal bacterium often found in laboratory mice, is required for Th17 cell biogenesis in the small intestine².

Building on these findings, Huh and Littman aim to understand the mechanisms by which prenatal exposure to an uncontrolled inflammatory environment leads to ASD phenotypes in offspring. To accomplish this, they will first investigate the roles of commensal bacteria of pregnant mice in inducing MIA phenotypes in their offspring. They will next identify commensal bacteria (from both mice and humans) that mediate MIA phenotypes in the mouse offspring. Finally, they will deplete the bacteria that induce Th17 cells in pregnant mice to determine if this has the potential to ameliorate MIA-associated behavioral phenotypes.

Positive results from this research will help support the notion that a prenatal inflammatory environment caused by microbiota-induced Th17 cell pathways serves as a major factor in the etiology of ASD. Moreover, such results could potentially be clinically significant, as they may offer new approaches for treating inflammation-associated ASD.