Maternal Microbiota and Immune Interactions in Neurodevelopmental Risk: A Review of Maternal Immune Activation Models

Abstract

Maternal Immune Activation (MIA) is a model used to study the impact of maternal infection and maternal inflammatory cues on fetal brain development and vulnerability to neurodevelopmental disorders (NDDs). Studies using the MIA model have confirmed the role of immune mediators, such as interleukin-17A (IL-17A), in disrupting the cortex's structural integrity and behavior. The maternal microbiota has also been recognized as a key modulator of these immune-fetal brain interactions. Microbes that inhabit the gut control TH17 cell differentiation—long-term players in MIA—and presence or absence can determine whether offspring become NDD-like following maternal inflammation. This association suggests the capacity of the microbiota to modulate maternal immune reactivity and thereby determine fetal neurodevelopmental processes. Together, these findings position MIA not as a singular immune event but as a systems-level interaction among microbes, cytokines, placental signaling, and fetal neuroimmune development.