Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that affects one in 45 children in the United States, with a similarly striking prevalence in countries around the world. However, mechanisms underlying its etiology and manifestations remain poorly understood. Although ASD is diagnosed based on the presence and severity of impaired social communication and repetitive behavior, immune dysregulation and gastrointestinal issues are common comorbidities. The microbiome is an integral part of human physiology; recent studies show that changes in the gut microbiota can modulate gastrointestinal physiology, immune function, and even behavior. Links between particular bacteria from the indigenous gut microbiota and phenotypes relevant to ASD raise the important question of whether microbial dysbiosis plays a role in the development or presentation of ASD symptoms. Here we review reports of microbial dysbiosis in ASD. We further discuss potential effects of the microbiota on ASD-associated symptoms, drawing on signaling mechanisms for reciprocal interactions among the microbiota, immunity, gut function, and behavior. In addition, we discuss recent findings supporting a role for the microbiome as an interface between environmental and genetic risk factors that are associated with ASD. These studies highlight the integration of pathways across multiple body systems that together can impact brain and behavior and suggest that changes in the microbiome may contribute to symptoms of neurodevelopmental disease.

Keywords: Autism; Gastrointestinal tract; Gut-brain axis; Inflammation; Microbiota; Neurodevelopment.

Figure 1. Model for Roles of the Microbiome in Autism Spectrum Disorder

The microbiota is shaped by host genetics and environmental exposures. Select genetic and environmental risk factors for ASD could directly cause changes in the indigenous microbiota. Alternatively, the microbiota could be indirectly influenced by other medical co-morbidities associated with ASD, including gastrointestinal issues and immune dysfunction. The microbiota exhibits reciprocal interactions with the gastrointestinal tract, immune system, brain and behavior and abnormalities in any one component of this integrated system could the others. In particular, dysbiosis of the intestinal microbiota, in addition to immune and gastrointestinal symptoms seen in ASD, can influence neurodevelopment, neural activity and the manifestation of abnormal behaviors characteristic to ASD.