Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

Gut ◽  
2021 ◽  
pp. gutjnl-2020-324015
Author(s):  
Yating Wan ◽  
Tao Zuo ◽  
Zhilu Xu ◽  
Fen Zhang ◽  
Hui Zhan ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Chinese Children ◽  
Chronological Age ◽  
Microbiome Composition ◽  
Children With Asd ◽  
Faecal Microbiome

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.DesignWe performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.ResultsASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.ConclusionsGut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

scholarly journals Serum Oxytocin Level Correlates With Gut Microbiome Dysbiosis in Children With Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Minshi Huang ◽  
Kevin Liu ◽  
Zhen Wei ◽  
Zhe Feng ◽  
Jierong Chen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Children With Autism ◽  
Preliminary Evidence ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Enzyme Linked Immunosorbent Assay ◽  
Children With Asd ◽  
New Findings

To investigate the levels of serum oxytocin (OT) in children with autism spectrum disorder (ASD) and explore the association between OT levels and gut microbiota relative abundances, we recruited 39 children with ASD children–mother dyads and 44 healthy controls. Serum OT levels were determined via enzyme-linked immunosorbent assay and gut microbiota abundances were determined by 16S rRNA sequencing. We found that the OT level of ASD was lower than the healthy control group overall (P &lt; 0.05). Furthermore, we present preliminary evidence of gut microbiome dysbiosis observed among children with ASD to lower levels of OT based on correlational analysis between serum OT and specific gut microbiota abundances (P &lt; 0.05). We also found sex-related differences in serum OT levels and GIS index (P &lt; 0.05). However, the generalizability of findings relevant to females with ASD require further validation in future studies involving larger sample sizes and balanced sex distributions due to the small number of females involved in this study. Nonetheless, these new findings further our understanding of the effects of low serum OT levels among individuals with ASD, which provides preliminary evidence in hopes of guiding future study design or mechanistic studies. The findings of the present study may be suggestive of potential ASD subtypes based on ASD severity and gut microbiome composition that may facilitate the prediction of the therapeutic responses of OT among those with ASD.

scholarly journals Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 792 ◽  
Author(s):  
Lucía Iglesias-Vázquez ◽  
Georgette Van Ginkel Riba ◽  
Victoria Arija ◽  
Josefa Canals
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Psychiatric Symptoms ◽  
Meta Analysis ◽  
Public Health Problem ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Lower Percentage ◽  
Children With Asd ◽  
Meta Analyses

Background: Autism spectrum disorder (ASD) is a public health problem and has a prevalence of 0.6%–1.7% in children. As well as psychiatric symptoms, dysbiosis and gastrointestinal comorbidities are also frequently reported. The gut–brain microbiota axis suggests that there is a form of communication between microbiota and the brain underlying some neurological disabilities. The aim of this study is to describe and compare the composition of gut microbiota in children with and without ASD. Methods: Electronic databases were searched as far as February 2020. Meta-analyses were performed using RevMan5.3 to estimate the overall relative abundance of gut bacteria belonging to 8 phyla and 17 genera in children with ASD and controls. Results: We included 18 studies assessing a total of 493 ASD children and 404 controls. The microbiota was mainly composed of the phyla Bacteroidetes, Firmicutes, and Actinobacteria, all of which were more abundant in the ASD children than in the controls. Children with ASD showed a significantly higher abundance of the genera Bacteroides, Parabacteroides, Clostridium, Faecalibacterium, and Phascolarctobacterium and a lower percentage of Coprococcus and Bifidobacterium. Discussion: This meta-analysis suggests that there is a dysbiosis in ASD children which may influence the development and severity of ASD symptomatology. Further studies are required in order to obtain stronger evidence of the effectiveness of pre- or probiotics in reducing autistic behaviors.

scholarly journals The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4497
Author(s):  
Michelle A. Chernikova ◽  
Genesis D. Flores ◽  
Emily Kilroy ◽  
Jennifer S. Labus ◽  
Emeran A. Mayer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Preclinical Research ◽  
Gastrointestinal Problems ◽  
The Brain

Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.

scholarly journals Gut Microbial Profile Is Associated With the Severity of Social Impairment and IQ Performance in Children With Autism Spectrum Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Zilin Chen ◽  
Kai Shi ◽  
Xin Liu ◽  
Yuan Dai ◽  
Yuqi Liu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Rating Scale ◽  
Alpha Diversity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Impairment ◽  
Clear Correlation ◽  
Specific Symptom ◽  
Children With Asd

Background and Objective: Autism spectrum disorder (ASD) refers to a heterogeneous set of neurodevelopmental disorders with diverse symptom severity and comorbidities. Although alterations in gut microbiota have been reported in individuals with ASD, it remains unclear whether certain microbial pattern is linked to specific symptom or comorbidity in ASD. We aimed to investigate the associations between gut microbiota and the severity of social impairment and cognitive functioning in children with ASD.Methods: A total of 261 age-matched children, including 138 children diagnosed with ASD, 63 with developmental delay or intellectual disability (DD/ID), and 60 typically developing (TD) children, were enrolled from the Shanghai Xinhua Registry. The children with ASD were further classified into two subgroups: 76 children diagnosed with ASD and developmental disorder (ASD+DD) and 62 with ASD only (ASD-only). The gut microbiome of all children was profiled and evaluated by 16S ribosomal RNA sequencing.Results: The gut microbial analyses demonstrated an altered microbial community structure in children with ASD. The alpha diversity indices of the ASD+DD and ASD-only subgroups were significantly lower than the DD/ID or TD groups. At the genus level, we observed a decrease in the relative abundance of Prevotella. Simultaneously, Bacteroides and Faecalibacterium were significantly increased in ASD compared with DD/ID and TD participants. There was a clear correlation between alpha diversity and the Childhood Autism Rating Scale (CARS) total score for all participants, and this correlation was independent of IQ performance. Similar correlations with the CARS total score were observed for genera Bacteroides, Faecalibacterium, and Oscillospira. However, there was no single genus significantly associated with IQ in all participants.Conclusions: Specific alterations in bacterial taxonomic composition and associations with the severity of social impairment and IQ performance were observed in children with ASD or ASD subgroups, when compared with DD/ID or TD groups. These results illustrate that gut microbiota may serve as a promising biomarker for ASD symptoms. Nevertheless, further investigations are warranted.

Autism Spectrum Disorder and Gut Microbiome: A Brief Review

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Aindrila Banerjee ◽  
Santi Ranjan Dey ◽  
Indrani Basu ◽  
Mitu De
Keyword(s):  
Autism Spectrum Disorder ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Oral Microbiota ◽  
Fecal Microbiota Transplant ◽  
Human Disorders ◽  
Health And Disease

The human microbiota consists of the 10-100 trillion symbiotic microbial cells harbored by each person, primarily bacteria in the gut. The association of the gut microbiota with human health and disease has been widely studied. A number of human disorders and diseases have been directly and indirectly associated with the microbiome. Children with Autism Spectrum Disorder (ASD) have distinctive gut microbiota compared to neurotypical children. Autism spectrum disorder (ASD) is associated with several oropharyngeal abnormalities, including dysbiosis in the oral microbiota. As there is a correlation between abnormal microbiota and development of autism like behaviour, so, modifying the gut microbiome by probiotics, prebiotics, antibiotics and fecal microbiota transplant (FMT) could be a potential route to improve GI and behavioural symptoms in children with ASD.

scholarly journals Children with Autism and Their Typically Developing Siblings Differ in Amplicon Sequence Variants and Predicted Functions of Stool-Associated Microbes

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Maude M. David ◽  
Christine Tataru ◽  
Jena Daniels ◽  
Jessey Schwartz ◽  
Jessica Keating ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Sample Size ◽  
Gut Microbiome ◽  
The United States ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sequence Variants ◽  
Sibling Pairs ◽  
Children With Asd ◽  
Matched Sibling

ABSTRACT The existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations, efforts to identify microbial biomarkers have been limited due to a lack of appropriately matched controls, stratification of participants within the autism spectrum, and sample size. To overcome these limitations, we crowdsourced the recruitment of families with age-matched sibling pairs between 2 and 7 years old (within 2 years of each other), where one child had a diagnosis of ASD and the other did not. Parents collected stool samples, provided a home video of their ASD child’s natural social behavior, and responded online to diet and behavioral questionnaires. 16S rRNA V4 amplicon sequencing of 117 samples (60 ASD and 57 controls) identified 21 amplicon sequence variants (ASVs) that differed significantly between the two cohorts: 11 were found to be enriched in neurotypical children (six ASVs belonging to the Lachnospiraceae family), while 10 were enriched in children with ASD (including Ruminococcaceae and Bacteroidaceae families). Summarizing the expected KEGG orthologs of each predicted genome, the taxonomic biomarkers associated with children with ASD can use amino acids as precursors for butyragenic pathways, potentially altering the availability of neurotransmitters like glutamate and gamma aminobutyric acid (GABA). IMPORTANCE Autism spectrum disorder (ASD), which now affects 1 in 54 children in the United States, is known to have comorbidity with gut disorders of a variety of types; however, the link to the microbiome remains poorly characterized. Recent work has provided compelling evidence to link the gut microbiome to the autism phenotype in mouse models, but identification of specific taxa associated with autism has suffered replicability issues in humans. This has been due in part to sample size that sufficiently covers the spectrum of phenotypes known to autism (which range from subtle to severe) and a lack of appropriately matched controls. Our original study proposes to overcome these limitations by collecting stool-associated microbiome on 60 sibling pairs of children, one with autism and one neurotypically developing, both 2 to 7 years old and no more than 2 years apart in age. We use exact sequence variant analysis and both permutation and differential abundance procedures to identify 21 taxa with significant enrichment or depletion in the autism cohort compared to their matched sibling controls. Several of these 21 biomarkers have been identified in previous smaller studies; however, some are new to autism and known to be important in gut-brain interactions and/or are associated with specific fatty acid biosynthesis pathways.

The Influence of Language Context on Repetitive Speech Use in Children With Autism Spectrum Disorder

2020 ◽  
Vol 29 (1) ◽  
pp. 327-334 ◽  
Author(s):  
Allison Gladfelter ◽  
Cassidy VanZuiden
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Individual Characteristics ◽  
Receptive Vocabulary ◽  
Spectrum Disorder ◽  
School Age Children ◽  
Social Responsiveness ◽  
Contributing Factors ◽  
Children With Asd ◽  
Language Context

Purpose Although repetitive speech is a hallmark characteristic of autism spectrum disorder (ASD), the contributing factors that influence repetitive speech use remain unknown. The purpose of this exploratory study was to determine if the language context impacts the amount and type of repetitive speech produced by children with ASD. Method As part of a broader word-learning study, 11 school-age children with ASD participated in two different language contexts: storytelling and play. Previously collected language samples were transcribed and coded for four types of repetitive speech: immediate echolalia, delayed echolalia, verbal stereotypy, and vocal stereotypy. The rates and proportions of repetitive speech were compared across the two language contexts using Wilcoxon signed-ranks tests. Individual characteristics were further explored using Spearman correlations. Results The children produced lower rates of repetitive speech during the storytelling context than the play-based context. Only immediate echolalia differed between the two contexts based on rate and approached significance based on proportion, with more immediate echolalia produced in the play-based context than in the storytelling context. There were no significant correlations between repetitive speech and measures of social responsiveness, expressive or receptive vocabulary, or nonverbal intelligence. Conclusions The children with ASD produced less immediate echolalia in the storytelling context than in the play-based context. Immediate echolalia use was not related to social skills, vocabulary, or nonverbal IQ scores. These findings offer valuable insights into better understanding repetitive speech use in children with ASD.

scholarly journals Parents’ Perceptions of Early Interventions and Related Services for Children with Autism Spectrum Disorder in Saudi Arabia

2016 ◽  
Vol 9 (10) ◽  
pp. 128 ◽  
Author(s):  
Faihan Alotaibi ◽  
Nabil Almalki
Keyword(s):  
Autism Spectrum Disorder ◽  
Saudi Arabia ◽  
Early Intervention ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Early Interventions ◽  
Related Services ◽  
Children With Asd ◽  
The Government

<p class="apa">The present study sought to examine parents’ perceptions of early interventions and related services for children with autism spectrum disorder (ASD) in Saudi Arabia. In this study a survey was distributed to a sample of 80 parents with children who have ASD. Parents also were asked open-ended questions to enable them to provide suggestions. The findings indicate that parents have varying perceptions of early interventions and related services. However, they seem to agree that these services are important in assisting their children. Accordingly, parents have suggested that the government needs to increase these services by providing more centers for children with ASD in Saudi Arabia, providing more specialists to deal with children with ASD, promoting inclusion in regular schools and providing more information on early intervention.</p>

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