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Gut microbiota changes in children with autism spectrum disorder: a systematic review.

ABSTRACT: Background:As more animal studies start to disentangle pathways linking the gut microbial ecosystem and neurobehavioral traits, human studies have grown rapidly. Many have since investigated the bidirectional communication between the gastrointestinal tract and the central nervous system, specifically on the effects of microbial composition on the brain and development. Methods:Our review at the initial stage aimed to evaluate literature on gut microbial alterations in pediatric neurobehavioral conditions. We searched five literature databases (Embase, PubMed, PsychInfo, Scopus, and Medline) and found 4489 published work. As the mechanisms linking gut microbiota to these conditions are divergent, the scope of this review was narrowed to focus on describing gut dysbiosis in children with autism spectrum disorder (ASD). Results:Among the final 26 articles, there was a lack of consistency in the reported gut microbiome changes across ASD studies, except for distinguishable patterns, within limits, for Prevotella, Firmicutes at the phylum level, Clostridiales clusters including Clostridium perfringens, and Bifidobacterium species. Conclusions:These results were inadequate to confirm a global microbiome change in children with ASD and causality could not be inferred to explain the etiology of the behaviors associated with ASD. Mechanistic studies are needed to elucidate the specific role of the gut microbiome in the pathogenesis of ASD.

SUBMITTER: Ho LKH

PROVIDER: S-EPMC6996179 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gut microbiota changes in children with autism spectrum disorder: a systematic review.

Ho Lucius Kang Hua LKH Tong Valerie Jia Wei VJW Syn Nicholas N Nagarajan Niranjan N Tham Elizabeth Huiwen EH Tay Stacey K SK Shorey Shefaly S Tambyah Paul Anantharajah PA Law Evelyn Chung Ning ECN

Gut pathogens 20200203

<h4>Background</h4>As more animal studies start to disentangle pathways linking the gut microbial ecosystem and neurobehavioral traits, human studies have grown rapidly. Many have since investigated the bidirectional communication between the gastrointestinal tract and the central nervous system, specifically on the effects of microbial composition on the brain and development.<h4>Methods</h4>Our review at the initial stage aimed to evaluate literature on gut microbial alterations in pediatric n ...[more]

PMID: 32025243

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Project description:Changes in the gut microenvironment may influence the pathogenesis of autism spectrum disorders (ASD). Here, we investigated the composition of the gut microbiota and metabolites in children with ASD. Ninety-two children with ASD and 42 age-matched children exhibiting typical development (TD) were enrolled in the two-stage study. In the discovery stage, shotgun metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS) were performed simultaneously on fecal samples obtained from 43 children in the ASD group and 31 children in the TD group. Systematic bioinformatic analyses were performed to identify gut metabolites associated with altered gut microbiota composition. At the validation stage, differential metabolites were tested using LC-MS with an additional 49 and 11 children in the ASD and TD groups, respectively. Altered glutamate metabolites were found in the ASD group, along with a decline in 2-keto-glutaramic acid and an abundance of microbiota associated with glutamate metabolism. These changes in glutamate metabolism were correlated with lower levels of the highly abundant bacteria Bacteroides vulgatus and higher levels of the potentially harmful Eggerthella lenta and Clostridium botulinum. Lower gut cortisol levels have also been identified in the ASD group and associated with changes in gut microbiota glutamate metabolism. Finally, gut 2-keto-glutaramic acid was validated as a potential biomarker for ASD. The significant changes in the gut microenvironment in children with ASD may provide new insight into the cause of ASD and aid in the search for diagnostic and therapeutic approaches. IMPORTANCE Multiple lines of evidence suggest that the gut microbiota may play an important role in the pathogenesis of ASD, but the specific mechanism is still unclear. Through a comprehensive gut metagenomic and metabolome study of children with ASD, alterations in gut metabolite composition were found in children with ASD, and these alterations were linked to changes in gut microbiota composition. This may give us a deeper understanding of the role of gut microbiota in the pathogenesis of ASD.

Project description:BackgroundFecal microbiota transplantation (FMT) may be helpful in the treatment of autism spectrum disorder (ASD) as rebalancing the gut microbiome has been shown to potentially improve behavioral symptoms in children with ASD.MethodsThis systematic review was conducted to assess the effect of FMT for children with ASD. The Embase, PubMed, Web of Science, and Cochrane Library databases were searched for articles published from inception to October 6, 2022. Two reviewers independently screened the identified records and undertook data extraction.ResultsThe search identified a total of five studies: two prospective open-label studies, two retrospective observational studies, and a case report; however, no randomized controlled trial was identified. All five studies reported a significant post-FMT-treatment improvement in neuropsychological assessment of ASD. The two prospective open-label studies suggested that the Autism Behavior Checklist (ABC) score, and the Social Responsiveness Scale (SRS) score at the posttreatment assessment decreased from the baseline (Wilcoxon signed-rank test; all p < 0.01]). The two retrospective observational studies suggested that FMT helped to improve the ASD symptoms. One observational study reported that the Childhood Autism Rating Scale (CARS) score and ABC score of the constipation group decreased from the baseline after the second course assessment (CARS [baseline: mean 35.25 ± standard deviation 4.36, second course: 32.5 ± 3.1, p = 0.015]; ABC [baseline: 56.21 ± 16.08, second course: 46.54 ± 16.54, p = 0.046]). Another observational study found that both ABC and CARS scores decreased as the number of FMT courses increased, and significant differences were found at the end of each course as compared with the baseline.ConclusionCompared with the baseline, FMT significantly improved symptoms of autism in children with ASD in observational studies. However, rigorously designed randomized controlled clinical trials are needed to establish the safety and efficacy of FMT as a treatment for ASD.

Project description:BackgroundChildren diagnosed with autism spectrum disorder (ASD) frequently suffer from persistent gastrointestinal symptoms, such as constipation and diarrhea. Various studies have highlighted differences in gut microbiota composition between individuals with ASD and healthy controls of similar ages. However, it's essential to recognize that these disparities may be influenced by cultural practices, dietary habits, and environmental factors.MethodsIn this study, we collected fecal samples from both children diagnosed with ASD (n = 42) and healthy individuals (n = 41) residing in the southeastern coastal region of China. Subsequently, 16 S rRNA gene sequencing and advanced bioinformatics analyses were conducted to investigate the distinctive features of gut microbial communities within each group.ResultsThe ASD group consisted of 28 males and 14 females, with a median age of 5.8 years, while the control group included 25 males and 16 females, with a median age of 6.8 years. Among the 83 sequenced fecal samples, a total of 1031 operational taxonomic units (OTUs) were identified. These included 122 unique OTUs specific to the control group and 285 unique OTUs specific to the ASD group. Analyses of α-diversity and β-diversity unveiled significant differences in the abundance and composition of gut microbiota between the two groups. It was found that the dominant bacterial taxa in healthy individuals were UBA1819, Flavonifractor, and Bradyrhizobium. In contrast, the ASD group exhibited a prevalence of Streptococcus, Ruminococcus, and Ruminiclostridium. Further analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Clusters of Orthologous Groups (COG) showed significant differences in the metabolic functionalities of the gut microbiota between the two groups. Notably, the metabolic pathway related to alpha-linolenic acid (ALA) in the gut microbiota of the ASD group was notably diminished compared to the control group. Conversely, the ASD group demonstrated significantly elevated levels of metabolic pathways involving uncharacterized conserved proteins, aminoglycoside phosphotransferase, and inorganic pyrophosphatase compared to the control group.ConclusionsOverall, these results confirm that there are significant differences in the gut microbiota structure between children with ASD and healthy controls in the southeast coastal region of China. This underscores the critical significance of delving into clinical interventions capable of mitigating the gastrointestinal and psychological symptoms encountered by children with ASD. A particularly encouraging path for such interventions lies in the realm of fecal microbiota transplantation, a prospect that merits deeper inquiry.

Dataset Information

Gut microbiota changes in children with autism spectrum disorder: a systematic review.

Publications

Gut microbiota changes in children with autism spectrum disorder: a systematic review.

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