Deviated and early unsustainable stunted development of gut microbiota in children with autism spectrum disorder

ObjectiveRecent studies have provided insights into the gut microbiota in autism spectrum disorder (ASD); however, these studies were restricted owing to limited sampling at the unitary stage of childhood. Herein, we aimed to reveal developmental characteristics of gut microbiota in a large cohort of subjects with ASD combined with interindividual factors impacting gut microbiota.DesignA large cohort of 773 subjects with ASD (aged 16 months to 19 years), 429 neurotypical (NT) development subjects (aged 11 months to 15 years) were emolyed to determine the dynamics change of gut microbiota across different ages using 16S rRNA sequencing.ResultIn subjects with ASD, we observed a distinct but progressive deviation in the development of gut microbiota characterised by persistently decreased alpha diversity, early unsustainable immature microbiota, altered aboudance of 20 operational taxonomic units (OTUs), decreased taxon detection rate and 325 deregulated microbial metabolic functions with age-dependent patterns. We further revealed microbial relationships that have changed extensively in ASD before 3 years of age, which were associated with the severity of behaviour, sleep and GI symptoms in the ASD group. This analysis demonstrated that a signature of the combination of 2 OTUs, Veillonella and Enterobacteriaceae, and 17 microbial metabolic functions efficiently discriminated ASD from NT subjects in both the discovery (area under the curve (AUC)=0.86), and validation 1 (AUC=0.78), 2 (AUC=0.82) and 3 (AUC=0.67) sets.ConclusionOur large cohort combined with clinical symptom analysis highlights the key regulator of gut microbiota in the pathogenesis of ASD and emphasises the importance of monitoring and targeting the gut microbiome in future clinical applications of ASD.

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

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.789864 ◽

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.

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Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

Microorganisms ◽

10.3390/microorganisms8091369 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1369 ◽

Cited By ~ 2

Author(s):

Léa Roussin ◽

Naika Prince ◽

Paula Perez-Pardo ◽

Aletta D. Kraneveld ◽

Sylvie Rabot ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Clinical Studies ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Preclinical Studies ◽

Potential Implication ◽

Gi Symptoms

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.

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Gene variations in autism spectrum disorder are associated with alteration of gut microbiota, metabolites and cytokines

Gut Microbes ◽

10.1080/19490976.2020.1854967 ◽

2021 ◽

Vol 13 (1) ◽

pp. 1-16

Author(s):

Zhi Liu ◽

Xuhua Mao ◽

Zhou Dan ◽

Yang Pei ◽

Rui Xu ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Autism Spectrum ◽

Spectrum Disorder

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Attention deficit hyperactivity disorder (ADHD) symptoms, comorbid psychopathology, behaviour problems and gastrointestinal symptoms in children and adolescents with autism spectrum disorder

Irish Journal of Psychological Medicine ◽

10.1017/ipm.2020.135 ◽

2021 ◽

pp. 1-11

Author(s):

Geraldine Leader ◽

Roisín Moore ◽

June L. Chen ◽

Aoife Caher ◽

Sophia Arndt ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Children And Adolescents ◽

Short Form ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Behaviour Problems ◽

Adhd Symptoms ◽

Hyperactivity Disorder ◽

Gi Symptoms ◽

Comorbid Psychopathology

Abstract Objectives: The study aims to investigate attention deficit hyperactivity disorder (ADHD) symptoms, gastrointestinal (GI) symptoms, comorbid psychopathology and behaviour problems in children and adolescents with autism spectrum disorder (ASD). Methods: Parents of 147 children and adolescents with ASD aged 6–18 years completed the Conners 3 Parent-Short Form, Gastrointestinal Symptom Inventory, Behavior Problems Inventory-Short Form and Autism Spectrum Disorder-Comorbid for Children. Results: Fifty-six per cent of children and adolescents had a comorbid diagnosis of ADHD, yet over 70% presented with clinically significant ADHD symptoms. Forty per cent of participants received a diagnosis of ADHD before ASD and 25.6% received a diagnosis of ASD first. Relationships were found between ADHD symptoms and comorbid psychopathology, GI symptoms, and behaviour problems. Conclusions: The outcomes suggest that ADHD is being underestimated as a comorbid disorder of ASD. This may have implications on treatment and interventions for children and adolescents who have a diagnosis of both ASD and ADHD.

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Gut Bacteria Shared by Children and Their Mothers Associate with Developmental Level and Social Deficits in Autism Spectrum Disorder

mSphere ◽

10.1128/msphere.01044-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

Yu Chen ◽

Hui Fang ◽

Chunyan Li ◽

Guojun Wu ◽

Ting Xu ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Autism Spectrum ◽

Gut Bacteria ◽

Spectrum Disorder ◽

Developmental Level ◽

Social Deficits ◽

Microbial Structure

Gut microbiota may contribute to the pathogenesis and development of autism spectrum disorder. The maternal gut microbiota influences offspring gut microbial structure and composition.

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

Gut ◽

10.1136/gutjnl-2020-324015 ◽

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.

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Sa1925 – Alteration in Gut Microbiota is Associated with Dysregulation of Metabolism of Autism Spectrum Disorder in China

Gastroenterology ◽

10.1016/s0016-5085(19)37991-0 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-455-S-456

Author(s):

Zhou Dan ◽

Xuhua Mao ◽

Qisha Liu ◽

Xingyin Liu

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Autism Spectrum ◽

Spectrum Disorder

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The link between autism spectrum disorder and gut microbiota: A scoping review

Autism ◽

10.1177/1362361320913364 ◽

2020 ◽

Vol 24 (6) ◽

pp. 1328-1344 ◽

Cited By ~ 4

Author(s):

Amanda Nitschke ◽

Raywat Deonandan ◽

Anne TM Konkle

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Scoping Review ◽

Bacterial Species ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Exclusion Criteria ◽

The Past ◽

Gastrointestinal Distress ◽

Special Diets

Gut dysfunction and microbial dysbiosis comorbidities are of particular interest in recent autism research, as gastrointestinal distress is present in up to 90% of autism spectrum disorder cases and therefore may play a key role in the pathogenesis of this disorder. This scoping review aims to integrate the results of studies conducted in the past 6 years examining the association between gut microbiota and autism spectrum disorder, specifically with regard to the characterization of autism spectrum disorder microbiota and potential therapeutic interventions. Studies related to the gastrointestinal microbiome of subjects with autism spectrum disorder were identified through PubMed, SCOPUS, PsycInfo, and Google Scholar databases. Studies were screened and selected based on defined inclusion and exclusion criteria; 19 studies were included. Research continues to report differences between microbiota of individuals with autism spectrum disorder and controls; however, the types and abundances of bacteria present remain inconsistent. Promising treatment interventions for autism spectrum disorder, including special diets, dietary supplementation, and of particular interest, microbiota transfer therapy, are also being explored. Research regarding the link between gut microbiota and autism spectrum disorder renders exciting results; however, it is still in its infancy of investigation. Rigorous methodologies are required to support and strengthen the reliability of existing results, and to further our understanding of the pathogenesis of autism spectrum disorder. Lay abstract Gastrointestinal distress and gut microbial imbalances are commonly found in children with autism spectrum disorder, and therefore may play a key role in the development of the disorder. This scoping review aimed to examine the extent, range and nature of research conducted in the past 6 years that focused on furthering our understanding of autism spectrum disorder and its association with gut microbiota. A literature review was performed with predetermined key words. Studies were screened and selected based on defined inclusion and exclusion criteria. A total of 19 studies were included for final analysis. While there are continuous reports of differences in gut microbiota between autism spectrum disorder and neurotypical individuals, knowledge about the consistency in the presence and abundance of bacterial species, as well as metabolites, remains deficient. Treatments such as special diets, vitamin, prebiotic, probiotic, and microbiota transfer therapy show promising therapeutic potential, yet are in their infancy of investigation. Overall, further research with rigorous methodologies is required to support and strengthen the reliability of existing findings. Future research should aim to increase sample sizes, eliminate biases, and subgroup autism spectrum disorder groups to help accommodate for inter-individual variation. As increasing evidence of a unique autism spectrum disorder microbiome and metabolome is acquired, autism spectrum disorder-specific biomarkers can be identified. These biomarkers have great implications in terms of elucidating the molecular mechanisms of autism spectrum disorder, preventing the onset of autism spectrum disorder, and improving treatments for individuals with autism spectrum disorder.

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