Microbiota and Microglia Interactions in ASD.

ABSTRACT

Autism spectrum disorders (ASD) are serious, highly variable neurodevelopmental disorders, commonly characterized by the manifestation of specific behavioral abnormalities, such as stereotypic behaviors and deficits in social skills, including communication. Although the neurobiological basis for ASD has attracted attention in recent decades, the role of microglial cells, which are the main resident myeloid cell population in the brain, is still controversial and underexplored. Microglia play several fundamental roles in orchestrating brain development and homeostasis. As such, alterations in the intrinsic functions of these cells could be one of the driving forces responsible for the development of various neurodevelopmental disorders, including ASD. Microglia are highly sensitive to environmental cues. Amongst the environmental factors known to influence their intrinsic functions, the gut microbiota has emerged as a central player, controlling both microglial maturation and activation. Strikingly, there is now compelling data suggesting that the intestinal microbiota can play a causative role in driving the behavioural changes associated with ASD. Not only is intestinal dysbiosis commonly reported in ASD patients, but therapies targeting the microbiome can markedly alleviate behavioral symptoms. Here we explore the emerging mechanisms by which altered microglial functions could contribute to several major etiological factors of ASD. We then demonstrate how pre- and postnatal environmental stimuli can modulate microglial cell phenotype and function, underpinning the notion that reciprocal interactions between microglia and intestinal microbes could play a crucial role in ASD aetiology.