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

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.

Author(s):  
Eunmi Lee ◽  
Jeonghyun Cho ◽  
Ka Young Kim

Autism spectrum disorder (ASD) is a developmental disorder that begins in early childhood and has been associated with several environmental and genetic factors. We aimed to conduct two-side meta-analyses to determine the association between ASD and pre- and postnatal antibiotic exposure in childhood. We searched PubMed, Embase, Web of Science, and Cochrane Library for articles published up to February 2019. We evaluated observational studies that assessed the association between ASD and antibiotic exposure. Of 1459 articles, nine studies were used in the meta-analysis. We found that early antibiotic exposure, including pre- and postnatal, significantly increased the ASD risk in children. Furthermore, early antibiotic exposure, including pre- and postnatal, was significantly increased in children with ASD. Specifically, prenatal antibiotic exposure was significantly increased in children with ASD; however, postnatal antibiotic exposure was not. Our results indicate an association between ASD and early antibiotic exposure; specifically, that prenatal antibiotic exposure is an important risk factor of ASD in children.


2021 ◽  
Vol 11 (6) ◽  
pp. 488
Author(s):  
Daniel A Rossignol ◽  
Richard E Frye

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.


Gut ◽  
2021 ◽  
pp. gutjnl-2020-324015
Author(s):  
Yating Wan ◽  
Tao Zuo ◽  
Zhilu Xu ◽  
Fen Zhang ◽  
Hui Zhan ◽  
...  

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.


2012 ◽  
Vol 34 (2) ◽  
pp. 82-103 ◽  
Author(s):  
Rebecca G. Lieberman ◽  
Paul Yoder

The association between object play and intentional communication was examined in children with autism spectrum disorder (ASD). Meta-analysis of concurrent and longitudinal correlational studies revealed significant associations between object play and intentional communication in young children with ASD. One well-conducted and internally valid, randomized, controlled trial suggests a bidirectional causal relationship between object play and intentional communication. Further experiments are needed to replicate these findings and test a play-as-stronger-cause hypothesis. Findings of the review have implications for development and implementation of effective interventions for young children with ASD when communication is the target and play serves as the context for intervention strategies. One model for conceptualization of treatment is proposed.


2020 ◽  
Vol 76 (1) ◽  
pp. 16-29 ◽  
Author(s):  
Navya Bezawada ◽  
Tze Hui Phang ◽  
Georgina L. Hold ◽  
Richard Hansen

Introduction: Differences in microbiota composition in children with autism spectrum disorder (ASD) compared to unaffected siblings and healthy controls have been reported in various studies. This study aims to systematically review the existing literature concerning the role of the gut microbiota in ASD. Methods: An extensive literature search was conducted using MEDLINE and EMBASE databases to identify studies (January 1966 through July 2019). Results: A total of 28 papers were included. The studies ranged from 12 to 104 participants who were aged between 2 and 18 years from various geographical areas. Majority of studies included faecal samples; however, 4 studies examined mucosal biopsies from different sites. The heterogeneity in ASD diagnostic methodology, gut site sampled and laboratory methods used made meta-analysis inappropriate. Species reported to be significantly higher in abundance in autistic children included Clostridium, Sutterella, Desulfovibrio and Lactobacillus. The findings are however inconsistent across studies. In addition, ­potential confounding effects of antimicrobial use, gastrointestinal symptoms and diet on the gut microbiota are unclear due to generally poor assessment of these factors. Conclusion: It is clear that the gut microbiota is altered in ASD, although further exploration is needed on whether this is a cause or an effect of the condition.


2020 ◽  
Vol 50 (6) ◽  
pp. 894-919 ◽  
Author(s):  
Steve Lukito ◽  
Luke Norman ◽  
Christina Carlisi ◽  
Joaquim Radua ◽  
Heledd Hart ◽  
...  

AbstractBackgroundPeople with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities.MethodsSystematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods.ResultsEighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation.ConclusionsPeople with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lei Chen ◽  
Xiao-Jie Shi ◽  
Hua Liu ◽  
Xiao Mao ◽  
Lue-Ning Gui ◽  
...  

AbstractThere is increasing awareness that oxidative stress may be implicated in the pathophysiology of autism spectrum disorder (ASD). Here we aimed to investigate blood oxidative stress marker profile in ASD children by a meta-analysis. Two independent investigators systematically searched Web of Science, PubMed, and Cochrane Library and extracted data from 87 studies with 4928 ASD children and 4181 healthy control (HC) children. The meta-analysis showed that blood concentrations of oxidative glutathione (GSSG), malondialdehyde, homocysteine, S-adenosylhomocysteine, nitric oxide, and copper were higher in children with ASD than that of HC children. In contrast, blood reduced glutathione (GSH), total glutathione (tGSH), GSH/GSSG, tGSH/GSSG, methionine, cysteine, vitamin B9, vitamin D, vitamin B12, vitamin E, S-adenosylmethionine/S-adenosylhomocysteine, and calcium concentrations were significantly reduced in children with ASD relative to HC children. However, there were no significance differences between ASD children and HC children for the other 17 potential markers. Heterogeneities among studies were found for most markers, and meta-regressions indicated that age and publication year may influence the meta-analysis results. These results therefore clarified blood oxidative stress profile in children with ASD, strengthening clinical evidence of increased oxidative stress implicating in pathogenesis of ASD. Additionally, given the consistent and large effective size, glutathione metabolism biomarkers have the potential to inform early diagnosis of ASD.


2021 ◽  
Vol 15 ◽  
Author(s):  
Minshi Huang ◽  
Kevin Liu ◽  
Zhen Wei ◽  
Zhe Feng ◽  
Jierong Chen ◽  
...  

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.


2021 ◽  
Author(s):  
Longxi Li ◽  
Anni Wang ◽  
Qun Fang ◽  
Michelle E. Moosbrugger

Abstract Background: Autism spectrum disorder (ASD) symptoms are usually observed by the age of 2 years. However, the mechanism of ASD is still encompassed in a block box and no identified cure exists. Based on accumulating evidence, intensive early treatment such as physical activity or exercise can make a significant difference in the cognitive control and development in children with ASD. This study aims to update the knowledge on extant literature and explore the efficacy of physical activity intervention strategies (PAIS) on cognitive functions in children with ASD. Methods: A systematic review and network meta-analysis will be conducted following the preferred reporting items for systematic review and meta-analysis protocols for Network Meta-Analyses (PRISMA-NMA). Nine bibliographic databases (APA PsycInfo, Cochrane Central Register of Controlled Trials, Dimensions, ERIC, MEDLINE Complete, PubMed, Scopus, SPORTDiscus, Web of Science) will be systematically searched to screen eligible articles based on a series of inclusion and exclusion criteria. A study will be considered for inclusion if the study: (a) is not classified as a systematic review with or without meta-analysis; (b) is published from inception to date; (c) includes children aged 0-12 years with ASD; (d) quantitively measures cognitive outcomes; (e) treatment includes at least one PAIS. The internal validity and quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Statistical analyses will be produced in RStudio 3.6 with the BUGSnet package and Comprehensive Meta-Analysis 3.3. Discussion: This study will provide an updated review of the extant literature by using an appropriate network meta-analytic model and address the questions regarding efficacy of PAIS that significantly impact cognitive functions in children with ASD with implications for future decision making. Systematic review registration: PROSPERO CRD42021279054.


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