Abstract
Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder and characterized by stereotyped behavior and deficits in communication and social interactions. The emerging microbial knowledge has pointed to a potential link between gut microbiota dysbiosis and ASD. Evidence from animal and human studies showed that shifts in composition and activity of the gut microbiota may causally contribute to the etiopathogenesis of core symptoms in the ASD individuals with gastrointestinal tract disturbances and act on microbiota-gut-brain. In this review, we summarized the characterized gut bacterial composition of ASD and the involvement of gut microbiota and their metabolites in the onset and progression of ASD; the possible underlying mechanisms are also highlighted. Given this correlation, we also provide an overview of the microbial-based therapeutic interventions such as probiotics, antibiotics, fecal microbiota transplantation therapy, and dietary interventions and address their potential benefits on behavioral symptoms of ASD. The precise contribution of altering gut microbiome to treating core symptoms in the ASD needs to be further clarified. It seemed to open up promising avenues to develop microbial-based therapies in ASD.
Highlights
Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder with pervasive neurodevelopmental disability (Arakawa, 2020; Valentino et al, 2021)
The composition of gut microbiota in rodents showing features of ASD was detected in models of environmental risk factors such as valproic acid (VPA) exposure, maternal immune activation (MIA), maternal high-fat diet (MHFD) and p-Cresol exposure, idiopathic model for autism (BTBR mice), and monogenetic mutation mouse models of autism such as Shank3 KO mice, NLGN3R451C mutants, and EphB6 KO mice (Hsiao et al, 2013; Buffington et al, 2016; Newell et al, 2016; Liu et al, 2018; Tabouy et al, 2018; Cai et al, 2019; Hosie et al, 2019; Li et al, 2020; Bermudez-Martin et al, 2021; Zhong et al, 2020)
4.2.2 Treatment With Antibiotics in ASD Patients A prospective birth cohort with 116 ASD cases and 860 typically developing (TD) child controls found that the risk for ASD was attenuated in women who experienced MIA during pregnancy and received antibiotics, suggesting that antibiotic treatment during pregnancy in the context of MIA may protect against the increased risk for ASD in the offspring (Holingue et al, 2020)
Summary
Autism spectrum disorder (ASD) is defined as a complex heterogeneous disorder with pervasive neurodevelopmental disability (Arakawa, 2020; Valentino et al, 2021). The emerging microbial knowledge has pointed that the complex intestinal microbial community and their metabolic consequences may contribute to ASD etiopathogenesis of core symptoms, such as in central nervous system (CNS)-driven behaviors, in a very powerful way (Oh and Cheon, 2020). Several lines of studies suggest that microbial-based therapeutic interventions such as fecal microbiota transplantation (FMT), antibiotics, and probiotics have emerged as novel therapeutic strategies to improve core and associated ASD symptoms (Johnson et al, 2020; MartínezGonzález and Andreo- Martínez, 2020; Davies et al, 2021). Existing literature relevant to therapeutic interventions based on alteration of gut microbiota in ASD appears to fall within the following four domains: prebiotic/ probiotic/synbiotic, FMT, dietary interventions, and antibiotics. The literature on each domain will be reviewed and microbial-based therapeutic interventions in ASD patients will be highlighted in a comprehensive way
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