The Gut Microbiota and Oxidative Stress in Autism Spectrum Disorders (ASD)

Abstract

Autism spectrum disorders (ASDs) are a kind of neurodevelopmental disorder with rapidly increasing morbidity. In recent years, many studies have proposed a possible link between ASD and multiple environmental as well as genetic risk factors; nevertheless, recent studies have still failed to identify the specific pathogenesis. An analysis of the literature showed that oxidative stress and redox imbalance caused by high levels of reactive oxygen species (ROS) are thought to be integral parts of ASD pathophysiology. On the one hand, this review aims to elucidate the communications between oxidative stress, as a risk factor, and ASD. As such, there is also evidence to suggest that early assessment and treatment of antioxidant status are likely to result in improved long-term prognosis by disturbing oxidative stress in the brain to avoid additional irreversible brain damage. Accordingly, we will also discuss the possibility of novel therapies regarding oxidative stress as a target according to recent literature. On the other hand, this review suggests a definite relationship between ASD and an unbalanced gastrointestinal tract (GIT) microbiota (i.e., GIT dysbiosis). A variety of studies have concluded that the intestinal microbiota influences many aspects of human health, including metabolism, the immune and nervous systems, and the mucosal barrier. Additionally, the oxidative stress and GIT dysfunction in autistic children have both been reported to be related to mitochondrial dysfunction. What is the connection between them? Moreover, specific changes in the GIT microbiota are clearly observed in most autistic children, and the related mechanisms and the connection among ASD, the GIT microbiota, and oxidative stress are also discussed, providing a theory and molecular strategies for clinical practice as well as further studies.

Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary 1H-NMR Metabolomics Analysis

“…The taurine and hypotaurine metabolism pathway also differed significantly between the two groups. Oxidative stress imbalance is considered to be important components of the pathophysiology of ASD, and antioxidant therapy may improve the prognosis of ASD ( 45 , 46 ). Park et al reported that taurine, as an antioxidant and regulator of inflammation, might be a valid biomarker for ASD ( 47 ).…”

Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

“…This is not only due to their impact on the microglia and the BBB permeability, but also to the production of SCFAs. As mitochondrial fuels, they may contribute to the uncontrolled production of ROS/RONS, particularly when the mitochondrial function is already altered [ 157 ] and the synthesis of SCFAs is increased due to alterations in the microbial composition. In fact, some bacterial species are more active in the production of SCFAs, such as Bacteroides spp.…”

Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data

“…the evidence for markers of oxidative stress associated with glutathione metabolism, lipid peroxidation, protein oxidation, DNA oxidation and antioxidant enzyme activity has been comprehensively reviewed in recent years [45,[98][99][100][101][102][103]. In the context of neurodevelopment, this has significant implications for the redox regulation of neurogenesis.…”

“…Given that mitochondrial dysfunction is an established component of ASD aetiology, and that metabolic state plays a central role in neuronal differentiation, our review highlights a potentially important connection between mTORC1, oxidative phosphorylation and neuropathology in ASD. Finally, our review integrates all of the above with the thoroughly reviewed evidence for neuroinflammation and oxidative stress in ASD [49][50][51][52][98][99][100][101][102][103] by considering the role of mitochondrial metabolism in gliosis and microglial activation, and the downstream consequences for synaptogenesis, neuronal connectivity and behavioural phenotypes.…”