scholarly journals Altered Gut Microbiome in Autism Spectrum Disorder: Potential Mechanism and Implications for Clinical Intervention

2019 ◽  
pp. 45-52 ◽  
Author(s):  
Kuokuo Li ◽  
Zhengmao Hu ◽  
Jianjun Ou ◽  
Kun Xia
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiome ◽  
Neurodevelopmental Disorder ◽  
Clinical Intervention ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Biological Interactions ◽  
Microbial Composition ◽  
Model Studies ◽  
Microbial Dysbiosis

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with an increased prevalence around the world over the past two decades. Remarkably, a large number of individuals with ASD have gastrointestinal disorders. Recent studies demonstrate that the endogenous gut microbiota has a close relationship with ASD according to the analyses of human host intestinal microbial composition and animal model studies. Here, we review the reports of microbial dysbiosis in ASD and then discuss the recent evidence of biological interactions among microbiota, metabolism, immunity, neurodevelopment, and behaviors. We also describe the role of the gut microbiome in the link between ASD and environmental risk factors. Finally, we suggest adjuvant treatments to consider in attempts to correct autistic behaviors.

scholarly journals Effects of gene by microbiome interactions on behavioral and neurobiological phenotypes in a mouse model for autism spectrum disorder

2020 ◽  
Author(s):  
Aya Osman ◽  
Nicholas L. Mervosh ◽  
Ana N. Strat ◽  
Katherine R. Meckel ◽  
Tanner J. Euston ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Mouse Model ◽  
Translational Research ◽  
Gut Microbiome ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Research Strategies ◽  
Stage Of Development

AbstractAutism spectrum disorder (ASD) is a serious neurodevelopmental disorder with a very high prevalence rate and a chronic disease course beginning in early childhood. Despite the tremendous burden of ASD, there are currently no disease-modifying treatments. Like many neuropsychiatric illnesses ASD has a complex pathophysiology driven by genetic and environmental factors. There is interest in identifying modifiable environmental factors as potential translational research strategies for development of therapeutics for ASD. A rapidly growing body of research demonstrates that the resident bacteria of the gastrointestinal tract, collectively the gut microbiome, have profound influence on brain and behavior. This gut-brain signaling pathway is highly relevant to ASD as the microbiome begins to form at birth, is heavily influenced by environmental factors throughout early life, and begins to stabilize at the same stage of development that symptoms of ASD begin to develop. To investigate potential gene x microbiome interactions in a model of ASD, we utilized mutant mice carrying a deletion of the ASD-associated Shank3 gene (Shank3KO), which clinically manifests as Phelan-McDermid syndrome, as a model for genetic risk of ASD. Analysis of the gut microbiome of Shank3KO mice demonstrated genotype effects on both microbiome composition and metabolite production. Behaviorally, Shank3KO mice demonstrate decreased social interactions and have altered anxiety and compulsive-like behaviors. Disruption of the microbiome with broad spectrum antibiotics lead to an exacerbation of all behavioral phenotypes in Shank3KO mice. Additionally, we found that Shank3KO mice had markedly increased changes in gene expression in the prefrontal cortex following microbiome depletion. Taken together, our results suggest a gene x microbiome interaction in this mouse model for ASD and raise the possibility that targeting the microbiome may be a valid translational research strategy in developing therapeutics for ASD.

scholarly journals The Role of Microbiome, Dietary Supplements, and Probiotics in Autism Spectrum Disorder

2020 ◽  
Vol 17 (8) ◽  
pp. 2647 ◽  
Author(s):  
Bhagavathi Sundaram Sivamaruthi ◽  
Natarajan Suganthy ◽  
Periyanaina Kesika ◽  
Chaiyavat Chaiyasut
Keyword(s):  
Autism Spectrum Disorder ◽  
Dietary Supplements ◽  
Maternal Diet ◽  
Neurodevelopmental Disorder ◽  
Critical Role ◽  
Food Preferences ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Microbial Composition

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by the impairment of the cognitive function of a child. Studies suggested that the intestinal microbiota has a critical role in the function and regulation of the central nervous system, neuroimmune system and neuroendocrine system. Any adverse changes in the gut–brain axis may cause serious disease. Food preferences and dietary patterns are considered as key in influencing the factors of ASD development. Several recent reviews narrated the importance of dietary composition on controlling or reducing the ASD symptoms. It has been known that the consumption of probiotics confers several health benefits by positive amendment of gut microbiota. The influence of probiotic intervention in children with ASD has also been reported and it has been considered as an alternative and complementary therapeutic supplement for ASD. The present manuscript discusses the role of microbiota and diet in the development of ASD. It also summarizes the recent updates on the influence of dietary supplements and the beneficial effect of probiotics on ASD symptoms. An in-depth literature survey suggested that the maternal diet and lifestyle are greatly associated with the development of ASD and other neurodevelopmental disorders. Mounting evidences have confirmed the alteration in the gut microbial composition in children suffering from ASD. However, the unique profile of microbiome has not yet been fully characterized due to the heterogeneity of patients. The supplementation of probiotics amended the symptoms associated with ASD but the results are inconclusive. The current study recommends further detailed research considering the role of microbiome, diet and probiotics in the development and control of ASD.

Specialized Diet Therapies: Exploration for Improving Behavior in Autism Spectrum Disorder (ASD)

2020 ◽  
Vol 27 (40) ◽  
pp. 6771-6786
Author(s):  
Geir Bjørklund ◽  
Nagwa Abdel Meguid ◽  
Maryam Dadar ◽  
Lyudmila Pivina ◽  
Joanna Kałużna-Czaplińska ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorder ◽  
Caloric Intake ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Nutritional Deficiencies ◽  
Childhood And Adolescence ◽  
Restricted Interests ◽  
Balanced Diet ◽  
The Individual

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

scholarly journals Intranasal oxytocin administration ameliorates social behavioral deficits in a POGZWT/Q1038R mouse model of autism spectrum disorder

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kohei Kitagawa ◽  
Kensuke Matsumura ◽  
Masayuki Baba ◽  
Momoka Kondo ◽  
Tomoya Takemoto ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Behavior ◽  
Mouse Model ◽  
Mouse Models ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
De Novo Mutation ◽  
Behavioral Deficits

AbstractAutism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by core symptoms of impaired social behavior and communication. Recent studies have suggested that the oxytocin system, which regulates social behavior in mammals, is potentially involved in ASD. Mouse models of ASD provide a useful system for understanding the associations between an impaired oxytocin system and social behavior deficits. However, limited studies have shown the involvement of the oxytocin system in the behavioral phenotypes in mouse models of ASD. We have previously demonstrated that a mouse model that carries the ASD patient-derived de novo mutation in the pogo transposable element derived with zinc finger domain (POGZWT/Q1038R mice), showed ASD-like social behavioral deficits. Here, we have explored whether oxytocin (OXT) administration improves impaired social behavior in POGZWT/Q1038R mice and found that intranasal oxytocin administration effectively restored the impaired social behavior in POGZWT/Q1038R mice. We also found that the expression level of the oxytocin receptor gene (OXTR) was low in POGZWT/Q1038R mice. However, we did not detect significant changes in the number of OXT-expressing neurons between the paraventricular nucleus of POGZWT/Q1038R mice and that of WT mice. A chromatin immunoprecipitation assay revealed that POGZ binds to the promoter region of OXTR and is involved in the transcriptional regulation of OXTR. In summary, our study demonstrate that the pathogenic mutation in the POGZ, a high-confidence ASD gene, impairs the oxytocin system and social behavior in mice, providing insights into the development of oxytocin-based therapeutics for ASD.

scholarly journals In Silico Exploration of the Potential Role of Acetaminophen and Pesticides in the Etiology of Autism Spectrum Disorder

Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 97
Author(s):  
Tristan Furnary ◽  
Rolando Garcia-Milian ◽  
Zeyan Liew ◽  
Shannon Whirledge ◽  
Vasilis Vasiliou
Keyword(s):  
Autism Spectrum Disorder ◽  
Prenatal Exposure ◽  
Pesticide Exposure ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Biomedical Literature ◽  
Spectrum Disorder ◽  
Biological Processes ◽  
Genetic Associations ◽  
Increased Risk

Recent epidemiological studies suggest that prenatal exposure to acetaminophen (APAP) is associated with increased risk of Autism Spectrum Disorder (ASD), a neurodevelopmental disorder affecting 1 in 59 children in the US. Maternal and prenatal exposure to pesticides from food and environmental sources have also been implicated to affect fetal neurodevelopment. However, the underlying mechanisms for ASD are so far unknown, likely with complex and multifactorial etiology. The aim of this study was to explore the potential effects of APAP and pesticide exposure on development with regards to the etiology of ASD by highlighting common genes and biological pathways. Genes associated with APAP, pesticides, and ASD through human research were retrieved from molecular and biomedical literature databases. The interaction network of overlapping genetic associations was subjected to network topology analysis and functional annotation of the resulting clusters. These genes were over-represented in pathways and biological processes (FDR p < 0.05) related to apoptosis, metabolism of reactive oxygen species (ROS), and carbohydrate metabolism. Since these three biological processes are frequently implicated in ASD, our findings support the hypothesis that cell death processes and specific metabolic pathways, both of which appear to be targeted by APAP and pesticide exposure, may be involved in the etiology of ASD. This novel exposures-gene-disease database mining might inspire future work on understanding the biological underpinnings of various ASD risk factors.

scholarly journals Mealtime Behaviors and Food Preferences of Students with Autism Spectrum Disorder

Foods ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Hae Jin Park ◽  
Su Jin Choi ◽  
Yuri Kim ◽  
Mi Sook Cho ◽  
Yu-Ri Kim ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Nutrition Education ◽  
Neurodevelopmental Disorder ◽  
Food Preferences ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Online Questionnaire ◽  
Mealtime Behavior ◽  
High Level

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a lack of social communication and restrictive, repetitive behaviors or interests. This study aimed to examine the mealtime behaviors and food preferences of students with ASD. An online questionnaire on mealtime behavior and food preferences of ASD students was conducted by caregivers including parents, and the average age of ASD students was 14.1 ± 6.1. The analysis of mealtime behavior resulted in classification into three clusters: cluster 1, the “low-level problematic mealtime behavior group”; cluster 2, the “mid-level problematic mealtime behavior group”; and cluster 3, the “high-level problematic mealtime behavior group”. Cluster 1 included older students than other clusters and their own specific dietary rituals. Meanwhile, cluster 3 included younger students than other clusters, high-level problematic mealtime behavior, and a low preference for food. In particular, there were significant differences in age and food preference for each subdivided ASD group according to their eating behaviors. Therefore, the content and method of nutrition education for ASD students’ needs a detailed approach according to the characteristics of each group.

scholarly journals Contribution of Multiple Inherited Variants to Autism Spectrum Disorder (ASD) in a Family with 3 Affected Siblings

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1053
Author(s):  
Jasleen Dhaliwal ◽  
Ying Qiao ◽  
Kristina Calli ◽  
Sally Martell ◽  
Simone Race ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Rare Variants ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Compound Heterozygous ◽  
Variable Effect ◽  
Gabaergic Neurotransmission ◽  
High Heritability ◽  
Compound Heterozygous Variants

Autism Spectrum Disorder (ASD) is the most common neurodevelopmental disorder in children and shows high heritability. However, how inherited variants contribute to ASD in multiplex families remains unclear. Using whole-genome sequencing (WGS) in a family with three affected children, we identified multiple inherited DNA variants in ASD-associated genes and pathways (RELN, SHANK2, DLG1, SCN10A, KMT2C and ASH1L). All are shared among the three children, except ASH1L, which is only present in the most severely affected child. The compound heterozygous variants in RELN, and the maternally inherited variant in SHANK2, are considered to be major risk factors for ASD in this family. Both genes are involved in neuron activities, including synaptic functions and the GABAergic neurotransmission system, which are highly associated with ASD pathogenesis. DLG1 is also involved in synapse functions, and KMT2C and ASH1L are involved in chromatin organization. Our data suggest that multiple inherited rare variants, each with a subthreshold and/or variable effect, may converge to certain pathways and contribute quantitatively and additively, or alternatively act via a 2nd-hit or multiple-hits to render pathogenicity of ASD in this family. Additionally, this multiple-hits model further supports the quantitative trait hypothesis of a complex genetic, multifactorial etiology for the development of ASDs.

scholarly journals Perceptions of Autism Spectrum Disorder (ASD) Etiology among Parents of Children with ASD

2021 ◽  
Vol 18 (13) ◽  
pp. 6774
Author(s):  
Wei-Ju Chen ◽  
Zihan Zhang ◽  
Haocen Wang ◽  
Tung-Sung Tseng ◽  
Ping Ma ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Content Analysis ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Parental Perceptions ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Structured Interviews ◽  
Children With Asd ◽  
Religious Factors

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and restricted or repetitive behaviors. Parental perceptions of the etiology of their child’s ASD can affect provider–client relationships, bonding between parents and their children, and the prognosis, treatment, and management of children with ASD. Thus, this study sought to examine the perceptions of ASD etiology of parents of children with ASD. Methods: Forty-two parents of children diagnosed with ASD were recruited across Texas. Semi-structured interviews were conducted individually. All interviews were recorded and later transcribed verbatim for content analysis utilizing NVivo 12.0 (QSR International, Doncaster, Australia). Results: The content analysis identified the following themes regarding parental perceptions of ASD etiology: Genetic factors (40.5%), environmental factors (31.0%), problems that occurred during pregnancy or delivery (23.8%), vaccinations (16.7%), other health problems (7.1%), parental age at the time of pregnancy (4.8%), and spiritual or religious factors (2.4%). Conclusions: The parental perceptions of ASD etiology were diverse, but several views, such as vaccinations and spiritual or religious factors, were not based on scientific evidence. Health professionals and researchers can use these findings to develop and provide targeted education to parents who have children with ASD. Our findings also support policymakers in developing campaigns designed to increase parental ASD awareness and knowledge.

scholarly journals Ketogenic Dietary Therapies in Patients with Autism Spectrum Disorder: Facts or Fads? A Scoping Review and a Proposal for a Shared Protocol

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2057
Author(s):  
Costanza Varesio ◽  
Serena Grumi ◽  
Martina Paola Zanaboni ◽  
Martina Maria Mensi ◽  
Matteo Chiappedi ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Scoping Review ◽  
Pediatric Patients ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Dietary Interventions ◽  
Web Based ◽  
Potential Efficacy ◽  
Study Designs

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with increasing incidence. An expanding body of literature is examining connections between ASD and dietary interventions. Existing reports suggest a beneficial effect of ketogenic dietary therapies (KDTs) in improving behavioral symptoms in ASD. In this context, the purpose of this scoping review was to identify and map available evidence in the literature about the feasibility and potential efficacy of KDTs in pediatric patients with ASD and to inform clinical practice in the field. Moreover, based on the resulting data from the literature review, we aimed to provide a shared protocol to develop a personalized KDT intervention in patients with ASD. A comprehensive and structured web-based literature search was performed using PubMed and Scopus and it yielded 203 records. Seven papers were finally selected and included in the review. Data were abstracted by independent coders. High variability was identified in study designs and dietary aspects emerged among selected studies. Results supported the effectiveness of KDTs in promoting behavioral improvements. Clinical recommendations on which patients may benefit most from KDTs implementation and difficulties in dietary adherence were discussed.

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