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Autonomic Nervous System Neuroanatomical Alterations Could Provoke and Maintain Gastrointestinal Dysbiosis in Autism Spectrum Disorder (ASD): A Novel Microbiome–Host Interaction Mechanistic Hypothesis
Authors:Athanasios Beopoulos  Manuel Gea  Alessio Fasano  Franois Iris
Institution:1.Bio-Modeling Systems, Tour CIT, 3 Rue de l’Arrivée, 75015 Paris, France; (A.B.); (M.G.);2.Mucosal Immunology and Biology Research Center, Center for Celiac Research and Treatment, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children, Boston, MA 022114, USA;
Abstract:Dysbiosis secondary to environmental factors, including dietary patterns, antibiotics use, pollution exposure, and other lifestyle factors, has been associated to many non-infective chronic inflammatory diseases. Autism spectrum disorder (ASD) is related to maternal inflammation, although there is no conclusive evidence that affected individuals suffer from systemic low-grade inflammation as in many psychological and psychiatric diseases. However, neuro-inflammation and neuro–immune abnormalities are observed within ASD-affected individuals. Rebalancing human gut microbiota to treat disease has been widely investigated with inconclusive and contradictory findings. These observations strongly suggest that the forms of dysbiosis encountered in ASD-affected individuals could also originate from autonomic nervous system (ANS) functioning abnormalities, a common neuro–anatomical alteration underlying ASD. According to this hypothesis, overactivation of the sympathetic branch of the ANS, due to the fact of an ASD-specific parasympathetic activity deficit, induces deregulation of the gut–brain axis, attenuating intestinal immune and osmotic homeostasis. This sets-up a dysbiotic state, that gives rise to immune and osmotic dysregulation, maintaining dysbiosis in a vicious cycle. Here, we explore the mechanisms whereby ANS imbalances could lead to alterations in intestinal microbiome–host interactions that may contribute to the severity of ASD by maintaining the brain–gut axis pathways in a dysregulated state.
Keywords:autism spectrum disorder (ASD)  autonomic nervous system (ANS)  microbiome  dysbiosis  brain–  gut axis (BGA)  gastrointestinal (GI) tract  neurodevelopment
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