Microglia are increasingly implicated in autism spectrum disorder (ASD), but their role remains difficult to define because the available evidence is heterogeneous in cohort composition, developmental stage, sampled brain region, and experimental modality. This Review summarizes current evidence on three related aspects of ASD-relevant microglial biology: microglial heterogeneity, immunometabolic regulation, and synapse-related pathways.
Human postmortem studies, bulk transcriptomics, single-cell and spatial atlases, methylomic deconvolution, and in vivo neuroimmune imaging collectively support the presence of immune- and glia-associated alterations in at least a subset of ASD brains, but these findings do not support a single ASD-wide microglial phenotype. Instead, current evidence is more consistent with region-, stage-, sex-, and context-dependent microglial variation that should be interpreted together with neuronal, astrocytic, vascular, and broader tissue-level changes.
We further review how lipid handling, mitochondrial function, phagocytic-lysosomal load, and bioactive lipid signaling may influence microglial competence in ASD-relevant settings, while noting that much of the detailed mechanistic immunometabolism literature still derives from aging and neurodegeneration.
Frontiers in Immunology published a clinical update in Infectious Disease on 28 Apr 2026.
The item focuses on Microglia in autism spectrum disorder: heterogeneity, immunometabolism, and synapse-related pathways.
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