scholarly journals Gut Microbiome-Based Analysis of Lipid A Biosynthesis in Individuals with Autism Spectrum Disorder: An In Silico Evaluation

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 688
Author(s):  
Abdulkadir Yusif Maigoro ◽  
Soojin Lee

The link between autism spectrum disorder (ASD) and the gut microbiome has received much attention, with special focus on gut–brain-axis immunological imbalances. Gastrointestinal problems are one of the major symptoms of ASD and are thought to be related to immune dysregulation. Therefore, in silico analysis was performed on mined data from 36 individuals with ASD and 21 control subjects, with an emphasis on lipid A endotoxin-producing bacteria and their lipopolysaccharide (LPS) metabolic pathways. Analysis of enzyme distribution among the 15 most abundant genera in both groups revealed that almost all these genera utilized five early-stage enzymes responsible for catalyzing the nine conserved lipid A synthesis steps. However, Haemophilus and Escherichia, which were significantly more abundant in individuals with ASD than in the control subjects, possess a complete set of essential lipid A synthesis enzymes. Furthermore, the 10 genera with the greatest increase in individuals with ASD showed high potential for producing late-stage lipid A products. Collectively, these results suggested that the synthesis rate of immunogenic LPS end products is likely to increase in individuals with ASD, which may be related to their gastrointestinal symptoms and elevated inflammatory conditions.

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4497
Author(s):  
Michelle A. Chernikova ◽  
Genesis D. Flores ◽  
Emily Kilroy ◽  
Jennifer S. Labus ◽  
Emeran A. Mayer ◽  
...  

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.


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.


Autism ◽  
2021 ◽  
pp. 136236132110626
Author(s):  
Calliope Holingue ◽  
Ohemaa Poku ◽  
Danika Pfeiffer ◽  
Sarah Murray ◽  
M. Daniele Fallin

Gastrointestinal distress is a prevalent issue in the autism spectrum disorder community, with implications for the person living with autism spectrum disorder and their families. However, the experiences of families caring for a child with co-occurring autism spectrum disorder and gastrointestinal symptoms have not been explored to date. We conducted one-on-one semi-structured interviews with 12 parents of children with co-occurring autism spectrum disorder and gastrointestinal symptoms. Using an inductive analysis approach, drawing on phenomenology, we identified four major themes across interviews. First, parents reported that their child had difficulty verbally communicating the presence of gastrointestinal symptoms, leading parents to rely on bodily signs and non-verbal behaviors to recognize when their child was experiencing gastrointestinal distress (Theme 1). Next, gastrointestinal issues impacted the child’s well-being and the ability to participate in and fully engage in activities (Theme 2), and the family’s well-being (Theme 3). Finally, parents often experienced challenges with seeking accessible and quality healthcare for their child’s gastrointestinal problems (Theme 4). These findings elucidate the incredible toll that gastrointestinal symptoms have on the overall wellness of children with autism spectrum disorder and their families. Lay abstract Gastrointestinal problems are common in the autism spectrum disorder community and may affect both the person with autism spectrum disorder and their families. However, little research is available on the experiences of families who have a child with both autism spectrum disorder and gastrointestinal symptoms. We held one-on-one interviews with 12 parents of children who had both autism spectrum disorder and gastrointestinal symptoms. We analyzed the raw text responses from these interviews and identified four main themes. First, parents shared that their children had trouble verbally communicating when they were experiencing gastrointestinal symptoms (Theme 1). This led parents to use bodily signs, such as changes in the stool, and non-verbal behaviors, such as irritability, to recognize when their child was having gastrointestinal symptoms. Next, gastrointestinal issues affected both the child’s well-being and their ability to attend class and extracurricular or social activities (Theme 2). The gastrointestinal issues also affected the family’s routines, overall well-being, and their ability to go out and do activities together as a family (Theme 3). Finally, parents often had challenges receiving accessible and quality healthcare for their child’s gastrointestinal problems (Theme 4). Together, these findings highlight the enormous burden that gastrointestinal symptoms have on the wellness of children with autism spectrum disorder and their families.


2020 ◽  
Vol Volume 16 ◽  
pp. 1807-1815
Author(s):  
Kelly YC Lai ◽  
Patrick WL Leung ◽  
Se Fong Hung ◽  
Caroline KS Shea ◽  
Flora Mo ◽  
...  

2020 ◽  
Vol 70 (6) ◽  
pp. 887-896 ◽  
Author(s):  
Shwikar AbdelSalam Ahmed ◽  
Azza Mahmoud Elhefnawy ◽  
Hanan Galal Azouz ◽  
Yara Safwat Roshdy ◽  
Mona Hamdy Ashry ◽  
...  

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2128 ◽  
Author(s):  
Xuejun Kong ◽  
Jun Liu ◽  
Murat Cetinbas ◽  
Ruslan Sadreyev ◽  
Madelyn Koh ◽  
...  

Autism Spectrum Disorder (ASD) is a complex neurological and developmental disorder characterized by behavioral and social impairments as well as multiple co-occurring conditions, such as gastrointestinal abnormalities, dental/periodontal diseases, and allergies. The etiology of ASD likely involves interaction between genetic and environmental factors. Recent studies suggest that oral and gut microbiome play important roles in the pathogenesis of inflammation, immune dysfunction, and disruption of the gut–brain axis, which may contribute to ASD pathophysiology. The majority of previous studies used unrelated neurotypical individuals as controls, and they focused on the gut microbiome, with little attention paid to the oral flora. In this pilot study, we used a first degree-relative matched design combined with high fidelity 16S rRNA (ribosomal RNA) gene amplicon sequencing in order to characterize the oral and gut microbiotas of patients with ASD compared to neurotypical individuals, and explored the utility of microbiome markers for ASD diagnosis and subtyping of clinical comorbid conditions. Additionally, we aimed to develop microbiome biomarkers to monitor responses to a subsequent clinical trial using probiotics supplementation. We identified distinct features of gut and salivary microbiota that differed between ASD patients and neurotypical controls. We next explored the utility of some differentially enriched markers for ASD diagnosis and examined the association between the oral and gut microbiomes using network analysis. Due to the tremendous clinical heterogeneity of the ASD population, we explored the relationship between microbiome and clinical indices as an attempt to extract microbiome signatures assocociated with clinical subtypes, including allergies, abdominal pain, and abnormal dietary habits. The diagnosis of ASD currently relies on psychological testing with potentially high subjectivity. Given the emerging role that the oral and gut microbiome plays in systemic diseases, our study will provide preliminary evidence for developing microbial markers that can be used to diagnose or guide treatment of ASD and comorbid conditions. These preliminary results also serve as a starting point to test whether altering the oral and gut microbiome could improve co-morbid conditions in patients with ASD and further modify the core symptoms of ASD.


2020 ◽  
Vol 70 (10) ◽  
pp. 1649-1667 ◽  
Author(s):  
Hajar Owji ◽  
Mahboobeh Eslami ◽  
Navid Nezafat ◽  
Younes Ghasemi

2011 ◽  
Vol 42 (7) ◽  
pp. 1520-1525 ◽  
Author(s):  
Matthew J. Maenner ◽  
Carrie L. Arneson ◽  
Susan E. Levy ◽  
Russell S. Kirby ◽  
Joyce S. Nicholas ◽  
...  

2018 ◽  
Vol 21 (2) ◽  
pp. 5-12 ◽  
Author(s):  
NT Popov ◽  
DS Minchev ◽  
MM Naydenov ◽  
IN Minkov ◽  
TI Vachev

Abstract Circulating microRNAs (miRNAs) are emerging as promising diagnostic biomarkers for autism spectrum disorder (ASD), but their usefulness for detecting ASD remains unclear. Nowadays, development of promising biomarkers for ASD remains a challenge. Recently, dysregulation of the miRNAs expression in postmortem brain tissue, serum and peripheral blood, have been associated with ASD. Circulating miRNAs are known to be secreted by a number of different cells and can interpose delivery of information into receiver cells, thus affecting their functions. Based on this fact, it is supposed that serum miRNAs could be a novel class of biomarkers for prognosis or diagnosis of pathological disorders including ASD. In the current research, we investigated whether the expression patterns of circulating miRNAs showed dysregulation in subjects diagnosed with ASD. Expression levels of serum miR-328-3p and miR-3135a were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) method of subjects diagnosed with ASD in comparison with healthy control subjects. Our data showed that miR-328-3p and miR-3135a were substantially down-regulated in ASD patients than in those of healthy control subjects. Moreover, target gene analysis of altered serum miRNAs displayed that these molecules targeted 162 genes denoted as unique validated targets in the miRWalk database, 71 of which appear to participate in biological pathways involved in synaptic pathways and neurodegenerative condition such as Alzheimer, Huntington and Parkinson diseases. Finally, the results strongly suggested that dys-regulated serum miRNAs might be involved in molecular pathways associated with ASD and miR-328-3p and miR-3135a have the potential to be promising novel biomarkers for ASD.


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