Abstract
Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.
Highlights
Articles were obtained from PubMed, SCOPUS, PsycInfo, and Google Scholar databases, using the following keywords: gut microbiome, gut-brain-microbiome axis, autism, autism spectrum disorder, ASD, social behavior, social cognition, emotion processing, probiotics, fecal microbial transplantation, tryptophan metabolism, or neuroimaging
Previous research has shown an association between gut microbiota and various neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), depression, and obsessive-compulsive disorder [27], which often co-occur with ASD [28]
In a study investigating the role of the KYN pathway in ASD, Bryn et al [81] showed that children with ASD had significantly lower kynurenic acid (KA) serum levels, higher KYN/KA ratios, and higher quinolinic acid (QA) serum concentrations than typically developing (TD) children
Summary
A growing body of research suggests that gut microbiota may serve an important role in modulating brain function, social behavior, and ASD symptomatology; for a review, see [2]. While various genetic and environmental risk factors have been implicated in ASD, this review aims to analyze the putative mechanisms underlying how gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development. (1) the brain-gut-microbiome (BGM) system; (2) findings from current animal and human studies as they relate to behavioral and neurological impairments in ASD; (3) the potential for microbiota-targeted therapies in ASD; and (4) how alterations to the microbiome may influence the development of neural networks involved in social and emotional skills
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