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

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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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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Theory of Mind Deficit is Associated with Pretend Play Performance, but not Playfulness, in Children with Autism Spectrum Disorder

Hong Kong Journal of Occupational Therapy ◽

10.1016/j.hkjot.2016.09.002 ◽

2016 ◽

Vol 28 (1) ◽

pp. 43-52 ◽

Cited By ~ 2

Author(s):

Ping-Chen Chan ◽

Cheng-Te Chen ◽

Hua Feng ◽

Ya-Chen Lee ◽

Kuan-Lin Chen

Keyword(s):

Autism Spectrum Disorder ◽

Theory Of Mind ◽

Internal Control ◽

Rating Scale ◽

Pretend Play ◽

Children With Autism ◽

Autism Spectrum ◽

Free Play ◽

Spectrum Disorder ◽

Children With Asd

Objective/Background This study aimed to examine the relationships of theory of mind (ToM) to both pretend play and playfulness in children with autism spectrum disorder (ASD). Methods Twenty children with ASD aged between 3 years and 7.11 years were assessed with the ToM test, and then placed in a free play condition and a pretend play condition to assess pretend play and playfulness with the Child-Initiated Pretend Play Assessment and Test of Playfulness, respectively. In addition, the children's symptom severities of ASD and verbal abilities were also assessed with the Childhood Autism Rating Scale (CARS) and Receptive and Expressive Vocabulary Test—second edition, respectively. Results The results of the regression analysis confirmed that ToM significantly predicted pretend play variables, namely, Number of Object Substitutions (R2 = .158, p = .002) and Number of Imitated Actions (R2 = .175, p = .001), but not playfulness. The CARS score was a significant predictor of the Percentage of Elaborate Pretend Play Actions of pretend play (R2 = .075, p = .034), as well as the internal control (R2 = .125, p = .006) and framing (R2 = .071, p = .039) variables of playfulness. Conclusion The findings support the idea that children with ASD who have better ToM might be able to develop better pretend play, but not better playfulness, which might be more strongly related to their autistic severity.

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Investigation of the Relation Between Epithelial Barrier Function and Autism Symptom Severity in Children with Autism Spectrum Disorder

10.21203/rs.3.rs-270289/v1 ◽

2021 ◽

Author(s):

Kevser Nalbant ◽

Semih Erden ◽

Abdullah Yazar ◽

İbrahim Kılınç

Keyword(s):

Autism Spectrum Disorder ◽

Barrier Function ◽

Rating Scale ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Enzyme Linked Immunosorbent Assay ◽

Epithelial Barrier ◽

Control Group ◽

Epithelial Barrier Function ◽

Children With Asd

Abstract Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by limitations in mutual communication and social interaction as well as restricted, repetitive patterns of behaviors, interests, or activities. A number of biological abnormalities have been reported in ASD. Therefore the possible role of biological abnormalities in etiopathogenesis arouses research interest in this area. This is a case-control design study evaluating epithelial barrier function by comparing serum concentrations of occludin and zonulin in children with ASD (n = 60) and controls (n = 30). The Childhood Autism Rating Scale (CARS) was used to evaluate autistic symptom levels of all children. Serum occludin and zonulin levels were analyzed using an enzyme-linked immunosorbent assay. Serum occludin was significantly lower in children with ASD than in control subjects. In children with ASD, a decrease in occludin level was significantly associated with the disorder symptom levels item mean score (CARS total scores). Our findings showed that children with ASD had alterations in epithelial barrier function compared to the control group. The investigation of the mechanism underlying the different levels of occludin between ASD and controls may be of importance in clarifying the etiopathogenesis of ASD, as well as its follow-up and treatment.

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

Gut ◽

10.1136/gutjnl-2021-325115 ◽

2021 ◽

pp. gutjnl-2021-325115

Author(s):

Mingxing Lou ◽

Aihua Cao ◽

Cuiyuan Jin ◽

Kai Mi ◽

Xiyue Xiong ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Area Under The Curve ◽

Alpha Diversity ◽

Autism Spectrum ◽

Large Cohort ◽

Spectrum Disorder ◽

Metabolic Functions ◽

Gi Symptoms ◽

Developmental Characteristics

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

Nutrients ◽

10.3390/nu12030792 ◽

2020 ◽

Vol 12 (3) ◽

pp. 792 ◽

Cited By ~ 18

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.

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AUTISM SPECTRUM DISORDER AND ASSOCIATED FACTORS AMONG CHILDREN AGED 24-72 MONTHS IN QUANG NGAI PROVINCE

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2018.6.29 ◽

2018 ◽

Vol 8 (6) ◽

pp. 218-225

Author(s):

Duc Nguyen Tan ◽

Khue Luong Ngoc ◽

Vu Nguyen Thanh Quang ◽

Thang Vo Van

Keyword(s):

Autism Spectrum Disorder ◽

Rural Areas ◽

Urban Areas ◽

Rating Scale ◽

Total Sample ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Cross Sectional ◽

Children With Asd ◽

Red Flag

Introduction: Autism Spectrum Disorder (ASD) is a disability developed in the young age and lasts during the lifetime. Early diagnosis and timely interventions will help improve the situation and reduce consequences caused to persons with ASD, their families and society. Objectives: (1) To describe the prevalence of ASD of the children aged 24 – 72 months Quang Ngai Province; (2) To analyse some factors related to ASD of the children aged 24 – 72 months in Quang Ngai Province. Methodology: Cross sectional research on a total sample size of 74,308 children aged 24 – 72 months in Quang Ngai Province in a period of September to December 2016; doing interview the parents or care givers on the children’s family socio-economic characteristics; all the children were screened to examine ASD signs and standards using red flag signs, Modified-Checklist for Autism in Toddlers (M-CHAT) and Childhood Autism Rating Scale (CARS). Children were finally examined and clinically diagnosed using criteria Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5). Results: 280 children aged 24 – 72 months, account for 3.8‰, were detected as ASD. Among the children with ASD, 63.57% were diagnosed severe, 36.34% diagnosed medium and slight. The boys with ASD is 3.1 times higher than girls (p<0.01). The children with ASD in urban areas is almost two times higher than those in rural areas (p<0.01). No any statistically significant association between factors of ethnicity, religion, ages of pregnant mothers or mother’s smoking habits with the children with ASD. Conclusions: Children aged 24 – 72 months with ASD in Quang Ngai Province accounted for 3.8‰, rather similar to the ASD prevalence in other similar studies over the world. It is a need to more deeply study on some factors related to ASD among children aged 24-72 months in Quang Ngai province. Key words: Autism Spectrum Disorder, ASD, Red flag signs, M-CHAT, CARS

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Effect of Yoga Therapy on Neuromuscular Function and Reduction of Autism Severity in Children With Autism Spectrum Disorder

International Journal of Health Systems and Translational Medicine ◽

10.4018/ijhstm.2021010104 ◽

2021 ◽

Vol 1 (1) ◽

pp. 76-85

Author(s):

Soccalingam Artchoudane ◽

Meena Ramanathan ◽

Ananda Balayogi Bhavanani ◽

Partheeban Muruganandam ◽

Lakshmi Jatiya

Keyword(s):

Autism Spectrum Disorder ◽

Rating Scale ◽

Handgrip Strength ◽

Children With Autism ◽

Neuromuscular Function ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Autism Severity ◽

Yoga Therapy ◽

Children With Asd

Autism is characterized by dysfunction in motor execution and sensory perception that are linked with neuromuscular function (fN) for children with autism spectrum disorder (ASD). This article aims to evaluate effectiveness of yoga therapy (YT) on fN and autism severity in children with ASD. Sixty children were screened (age 6 to 18) using childhood autism rating scale (CARS); 40 were allocated randomly (n=20) into yoga (YG) and control (CG) groups; both followed regular school routine, and YG received 10 YT sessions (60 min/session). Visual reaction time (VRT), handgrip strength (HGS), and CARS were measured. YG showed significant changes in VRT and CARS after YT and intergroup comparisons revealed significant differences between groups at the end of the study (VRT,p=0.008; CARS,p=0.011). YT resulted in small but statistically significant changes in CARS and significant improvement in VRT. This implies that YT can be used as an adjuvant modality for children with ASD, reducing co-morbidities with regard to the neuromuscular function.

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

Frontiers in Neuroscience ◽

10.3389/fnins.2021.721884 ◽

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 < 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 < 0.05). We also found sex-related differences in serum OT levels and GIS index (P < 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.

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Autism Spectrum Disorder: Correlation between aberrant behaviors, EEG abnormalities and seizures

Neurology International ◽

10.4081/ni.2010.e10 ◽

2010 ◽

Vol 2 (1) ◽

pp. 10 ◽

Cited By ~ 28

Author(s):

Michelle Elena Hartley-McAndrew ◽

Arie Weinstock

Keyword(s):

Autism Spectrum Disorder ◽

Rating Scale ◽

Epileptiform Activity ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Control Group ◽

Epileptiform Discharges ◽

Children With Asd ◽

Eeg Abnormalities ◽

Significant Difference

The relationship between epilepsy, epileptiform discharges, cognitive, language and behavioral symptoms is not clearly understood. Since difficulties with socialization and maladaptive behaviors are found in children with Autism Spectrum Disorder (ASD), we inquired whether epileptiform activity and seizures are associated with adverse behavioral manifestations in this population. We reviewed our EEG database between 1999-2006, and identified 123 children with ASD. EEG abnormalities were found in 39 children (31%). A control group of age and gender matched ASD children with normal EEG’s was obtained. Packets of questionnaires including the Vineland Adaptive Behavior Scale II (VABS), Aberrant Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS) were sent by mail. Out of 21 packets received, 11 had normal and 10 had abnormal EEG’s. There were no statistically significant differences in behavior between the two groups. Statistical analysis of discharge location and frequency did not reveal a significant trend. However, children with ASD and seizures had statistically significant lower scores in VABS daily living (P=0.009) and socialization (P=0.007) as compared to those without seizures. ASD children with seizures had higher ABC levels of hyperactivity and irritability. Differences in irritability scores nearly reached statistical significance (P=0.058). There was no significant difference in the degree of CARS autism rating between the groups. Our study did not reveal statistically significant differences in behaviors between ASD children with and without EEG abnormalities. However, ASD children with seizures revealed significantly worse behaviors as compared to counterparts without seizures.

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Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.751575 ◽

2021 ◽

Vol 12 ◽

Author(s):

Tiantian Wang ◽

Ling Shan ◽

Chunyue Miao ◽

Zhida Xu ◽

Feiyong Jia

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Therapeutic Effect ◽

Rating Scale ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Children With Asd ◽

Core Symptoms ◽

Positive Effect

Background: The therapeutic effect of bumetanide on autism spectrum disorder (ASD) seems to be controversial. To obtain better evidence on the efficacy of bumetanide, a systematic review and meta-analysis were performed.Methods: Randomized, placebo-controlled trials (RCTs) of bumetanide treatment in children with ASD were identified through systematic review from database inception to January 17, 2021. Subsequently, a meta-analysis was carried out to examine the effect of bumetanide on the severity of symptoms of ASD as assessed by the Childhood Autism Rating Scale (CARS) and Social Responsive Scale (SRS); core symptoms according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 of the American Psychiatric Association [social affect (SA), restricted, repetitive patterns of behavior, interests, or activities (RRB) and sensory symptoms]; and the therapeutic effect as assessed by Clinical Global Impressions-Efficacy (CGI-E).Results: In total, six RCTs involving 496 participants with ASD were identified in our study. The results showed that bumetanide could significantly improve the severity of the ASD symptoms measured by CARS and SRS. There was also evidence that bumetanide had positive effect on the core symptoms of ASD such as the SA and RRB, but there was no statistically significant effect on sensory symptoms. A significant positive effect on CGI-E scores in ASD patients was also observed.Conclusion: Our meta-analysis provided some support that bumetanide could improve the symptoms of children with ASD. However, additional large-scale longitudinal studies that provide clearer information and better control for confounding factors are needed to confirm our findings.

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