Abstract
Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders defined by impaired social interactions and communication with repetitive behaviors, activities, or interests. Gastrointestinal (GI) disturbances and gut microbiota dysbiosis are frequently associated with ASD in childhood. However, it is not known whether microbiota dysbiosis in ASD patients also occurs in adulthood. Further, the consequences of altered gut microbiota on digestive functions and the enteric nervous system (ENS) remain unexplored. Therefore, we studied, in mice, the ability offecal supernatant (FS) from adult ASD patients to induce GI dysfunctions and ENS remodeling. First, the analyses of the fecal microbiota composition in adult ASD patients indicated a reduced α-diversity and increased abundance of three bacterial 16S rRNA gene amplicon sequence variants compared to healthy controls (HC). The transfer of FS from ASD patients (FS–ASD) to mice decreased colonic barrier permeability by 29% and 58% compared to FS–HC for paracellular and transcellular permeability, respectively. These effects are associated with the reduced expression of the tight junction proteins JAM-A, ZO-2, cingulin, and proinflammatory cytokines TNFα and IL1β. In addition, the expression of glial and neuronal molecules was reduced by FS–ASD as compared to FS-HC in particular for those involved in neuronal connectivity (βIII-tubulin and synapsin decreased by 31% and 67%, respectively). Our data suggest that changes in microbiota composition in ASD may contribute to GI alterations, and in part, via ENS remodeling.
Highlights
Autism spectrum disorder (ASD) is a heterogeneous group of neuro-developmental disorders causing life-long impairments defined by a lack of social skills, empathy, communication deficits, andpatterns of repetitive behaviors and restricted interests
Our findings support the possibility that alterations of gut microbiota may participate in gut disturbances in ASD by, in part, inducing enteric nervous system (ENS) remodeling
ASD [34,35,36], our work demonstrated that microbiota alterations are present in adults with ASD
Summary
Autism spectrum disorder (ASD) is a heterogeneous group of neuro-developmental disorders causing life-long impairments defined by a lack of social skills, empathy, communication deficits, andpatterns of repetitive behaviors and restricted interests. In neurodegenerative diseases, recent studies reported altered microbiota composition in Parkinson’s disease (PD) patients that could contribute to intestinal inflammatory conditions observed in PD patients [26]. Among putative mechanisms linking microbiota to PD progression, is the fact that the altered microbiota composition, in particular increased gram-negative bacteria found in PD, could contribute to the induction of an LPS-dependent inflammatory response of the gut and the brain leading to enhanced motor symptoms and dopaminergic damage [28,29]. Concerning ASD, several studies reported changes in the composition of fecal microbiota and bacteria-derived metabolites in ASD patients compared to neurotypical individuals [17,31,32,33,34,35,36]. ASD patients, as compared to healthy controls, could induce changes in GI functions and ENS remodeling
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