The microbiota–gut–brain axis and autism spectrum disorder: Microbiota-mediated mechanisms, metabolic dysregulation, and neurodevelopmental implications

Human cognitive functions depend on the complex interactions among multiple systems, including the microbiota‒gut‒brain axis and the hypothalamic‒pituitary‒adrenal axis. Autism spectrum disorder, as a complex neurobiological disorder, impairs social interaction and communication in patients, leading to repetitive and stereotyped patterns of behavior. Changes in the qualitative and quantitative composition of the gut microbiota in certain gastrointestinal diseases underscore the importance of changes in the gastrointestinal system in neuropsychiatric diseases. Microorganisms, especially gut microbes, are closely related to the pathophysiology of autism. There are significant differences in the composition of the gut microbiota between individuals with autism and healthy individuals. Various metabolites, many of which are bacterial metabolites, such as short-chain fatty acids and lipopolysaccharides, are altered in the blood and urine of patients with autism. In addition, changes in tight junctions of the blood‒brain barrier and the role of glial cells in regulating inflammatory responses and mediating neurodevelopment are also important. This review discusses the main mechanisms of action of the gut‒brain axis, elaborates on the impact of microorganisms on autism, and provides a new perspective for the prevention and research of autism.