scholarly journals A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

2020 ◽  
Vol 6 (43) ◽  
pp. eaba3760
Author(s):  
Mengxiang Zhang ◽  
Yanan Chu ◽  
Qingren Meng ◽  
Rui Ding ◽  
Xing Shi ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Potential Role ◽  
Autism Spectrum ◽  
Detoxifying Enzymes ◽  
Paired Samples ◽  
Diagnostic Models ◽  
Metagenomic Study ◽  
Toxin Accumulation ◽  
Microbial Detoxification

Growing evidence suggests that autism spectrum disorder (ASD) is strongly associated with dysbiosis in the gut microbiome, with the exact mechanisms still unclear. We have proposed a novel analytic strategy—quasi-paired cohort—and applied it to a metagenomic study of the ASD microbiome. By comparing paired samples of ASD and neurotypical subjects, we have identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which show a strong correlation with biomarkers of mitochondrial dysfunction. Diagnostic models based on these detoxifying enzymes accurately distinguished ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. In summary, our results suggest a previously undiscovered potential role of impaired intestinal microbial detoxification in toxin accumulation and mitochondrial dysfunction, a core component of ASD pathogenesis. These findings pave the way for designing future therapeutic strategies to restore microbial detoxification capabilities for patients with ASD.

scholarly journals A quasi-paired cohort strategy reveals the impaired detoxifying function of microbes in the gut of autistic children

2020 ◽  
Author(s):  
Mengxiang Zhang ◽  
Yanan Chu ◽  
Qingren Meng ◽  
Rui Ding ◽  
Xing Shi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Therapeutic Strategies ◽  
Strong Correlations ◽  
Detoxifying Enzymes ◽  
Paired Samples ◽  
Diagnostic Models ◽  
Analysis Strategy ◽  
Metagenomic Study ◽  
Microbial Detoxification

AbstractGrowing evidence suggests that autism spectrum disorder (ASD) is highly associated with dysbiosis in the gut microbiome. However, results of metagenome-based microbiome studies are not always consistent due to great individual diversity that overwhelms disease-associated alterations. Here, we proposed a novel analysis strategy—quasi-paired cohort and applied it to a metagenomic study of ASD microbiomes. By comparing the paired samples of ASD and neurotypical subjects, we identified significant deficiencies in ASD children in detoxifying enzymes and pathways, which showed strong correlations to mitochondrial damage. Diagnostic models with these detoxifying enzymes accurately discriminated ASD individuals from controls, and the dysfunction score inferred from the model increased with the clinical rating scores of ASD. Conclusively, our findings suggest a previously undiscovered mechanism in which impaired microbial detoxification leads to toxicant accumulation and mitochondrion damage contributes to the pathogenesis of ASD. This novel mechanism points to future therapeutic strategies of rebuilding microbial detoxification for ASD.

scholarly journals Role of NAD+, Oxidative Stress, and Tryptophan Metabolism in Autism Spectrum Disorders

2013 ◽  
Vol 6s1 ◽  
pp. IJTR.S11355 ◽  
Author(s):  
Musthafa Mohamed Essa ◽  
Selvaraju Subash ◽  
Nady Braidy ◽  
Samir Al-Adawi ◽  
Chai K Lim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Antioxidant Defense ◽  
Developmental Disorder ◽  
Repetitive Behavior ◽  
Autism Spectrum ◽  
Tryptophan Metabolism ◽  
Spectrum Disorders ◽  
Impaired Energy Metabolism

Autism spectrum disorder (ASD) is a pervasive neuro-developmental disorder characterized by impaired social interaction, reduced/absent verbal and non-verbal communication, and repetitive behavior during early childhood. The etiology of this developmental disorder is poorly understood, and no biomarkers have been identified. Identification of novel biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention. Studies suggest that oxidative stress-induced mechanisms and reduced antioxidant defense, mitochondrial dysfunction, and impaired energy metabolism (NAD+, NADH, ATP, pyruvate, and lactate), are major causes of ASD. This review provides renewed insight regarding current autism research related to oxidative stress, mitochondrial dysfunction, and altered tryptophan metabolism in ASD.

scholarly journals Pleiotropic actions of estrogen: a mitochondrial matter

2013 ◽  
Vol 45 (3) ◽  
pp. 106-109 ◽  
Author(s):  
Michael C. Velarde
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cellular Response ◽  
Estrogen Replacement Therapy ◽  
Potential Role ◽  
Estrogen Replacement ◽  
Beneficial Effects ◽  
Age Related ◽  
Pleiotropic Action ◽  
Pleiotropic Actions

Estrogen provides many beneficial effects early in life by regulating normal tissue development and several physiological functions. While estrogen replacement therapy (ERT) in women was expected to reduce the health risks associated with the age-related decline in estrogen levels during menopause, ERT also resulted in increased progression to other types of diseases. Hence, distinguishing the signaling pathways that regulate the beneficial and detrimental effects of estrogen is important for developing interventions that selectively harness the hormone's beneficial effects, while minimizing its side effects. Estrogen can minimize mitochondrial dysfunction, which is thought to contribute to aging phenotypes. Decline in estrogen levels during menopause may lead to progressive mitochondrial dysfunction and may permanently alter cellular response, including that of estrogen (i.e., ERT). This review discusses the interplay between estrogen and mitochondrial function during the aging process and suggests a potential role of mitochondria in influencing the pleiotropic action of estrogen.

scholarly journals Prospect of Mitochondria-Targeted Antioxidants as a Hepatoprotective and Anti-Alcoholic Liver Disease Agent

2021 ◽  
Author(s):  
Abugri James ◽  
Michael Adu-Frimpong
Keyword(s):  
Liver Disease ◽  
Mitochondrial Dysfunction ◽  
Alcoholic Liver Disease ◽  
Potential Role ◽  
Structural Integrity ◽  
Efficient Delivery ◽  
Disease Agent ◽  
Mitochondrial Oxidative Damage ◽  
Hepatoprotective Agents

Oxidative stress initiates and facilitates the disruption of the structural integrity of hepatic mitochondria, which leads to steatosis, steatohepatitis, fibrosis, and cirrhosis. It is now evident that mitochondrial dysfunction could be responsible for alcoholic liver disease (ALD). The challenge in treating ALD has been the limited availability of hepatoprotective agents and the lack of highly efficient delivery systems. Recent studies have shown that mitochondria-targeted therapies could address mitochondrial dysfunction (MD), which may greatly improve hepatoprotection and ALD treatment. This mini-review discusses the potential role of mitochondria-targeted antioxidants (MTAs) in the maintenance of hepatocellular integrity. This report also considers the mechanism of liver injury induced by alcohol and the progression of ALD from a mitochondrial oxidative damage perspective as well as the possible mechanistic actions of hepatoprotective antioxidants. Preliminary studies suggest the prospect of MTAs as anti-ALD and hepatoprotective agents.

scholarly journals Sensory Reactivity Phenotype in Phelan–McDermid Syndrome Is Distinct from Idiopathic ASD

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 977
Author(s):  
Teresa Tavassoli ◽  
Christina Layton ◽  
Tess Levy ◽  
Mikaela Rowe ◽  
Julia George-Jones ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Potential Role ◽  
Autism Spectrum ◽  
Typically Developing ◽  
Sensory Assessment ◽  
Sensory Reactivity ◽  
Dsm 5 ◽  
Main Driver ◽  
Insight Into

Phelan–McDermid syndrome (PMS) is one of the most common genetic forms of autism spectrum disorder (ASD). While sensory reactivity symptoms are widely reported in idiopathic ASD (iASD), few studies have examined sensory symptoms in PMS. The current study delineates the sensory reactivity phenotype and examines genotype–phenotype interactions in a large sample of children with PMS. Sensory reactivity was measured in a group of 52 children with PMS, 132 children with iASD, and 54 typically developing (TD) children using the Sensory Assessment for Neurodevelopmental Disorders (SAND). The SAND is a clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on the DSM-5 criteria for ASD. Children with PMS demonstrated significantly greater hyporeactivity symptoms and fewer hyperreactivity and seeking symptoms compared to children with iASD and TD controls. There were no differences between those with Class I deletions or sequence variants and those with larger Class II deletions, suggesting that haploinsufficiency of SHANK3 is the main driver of the sensory phenotype seen in PMS. The syndrome-specific sensory phenotype identified in this study is distinct from other monogenic forms of ASD and offers insight into the potential role of SHANK3 deficiency in sensory reactivity. Understanding sensory reactivity abnormalities in PMS, in the context of known glutamatergic dysregulation, may inform future clinical trials in the syndrome.

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