The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: a systematic review

Al-Ayadhi, Laila; Zayed, Naima; Bhat, Ramesa Shafi; Moubayed, Nadine; Al-Muammar, May N.; El‐Ansary, Afaf

doi:10.1186/s13099-021-00448-y

Cited by 40 publications

(47 citation statements)

References 129 publications

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“…When the ASD mice were treated with candidate microbial metabolites, their abnormal behaviour improved significantly, and the excitability of brain neurons were regulated [ 100 ]. A Systematic review found that altered gut microbiota in autistic children may trigger intestinal leakage, of which short-chain fatty acids, lipopolysaccharide, calprotectin, lysozyme and lysozyme can be used as biomarkers for early detection of intestinal leakage [ 101 ]. This indicates that gut microbiota could be a target for ASD treatment.…”

Section: Discussionmentioning

confidence: 99%

The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial

Zhang

et al. 2022

PLoS ONE

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Background Autism spectrum disorder (ASD) is a neurological and developmental condition that begins in infancy or earlier and lasts through the individual’s lifetime. The aetiology and mechanisms of ASD are not yet fully understood, and current treatment comprises mainly education and rehabilitation, without significant improvement in the core symptoms. Recent studies suggest that microbiota change in children with ASD after the ingestion of probiotics may improve the balance of microbiota and thus ASD symptoms. Objective The objectives of this study are to evaluate the efficacy of probiotics on the symptoms of children with ASD and the possible mechanisms involved. Methods This is a prospective controlled trial. A total of 160 children with ASD will be stratified and allocated to placebo and probiotics groups randomised according to the severity of their ASD symptoms. The probiotics group will be given probiotics supplements orally twice a day for 3 months and the control group will be given a placebo at the same amount, in addition to the baseline therapy of education and rehabilitation. All the children will be evaluated systematically by using different scales, questionnaires before, during, and after 3 months’ treatment, as well as 3 months after discontinuation. The potential impact of probiotics on immunity and inflammation, metabolism, and metagenome will also be investigated. Discussion Our previous study showed that the abundance of intestinal flora was greatly different in children with ASD, and that Bifidobacterium was associated with the severity of ASD. In the present study, we will investigate the impact of probiotics supplementation on the symptoms of Children with ASD, with the purpose of evaluating the possible therapeutic effects of additives on ASD and of providing a reference for clinical treatment. The results will help to disclose as yet unknown relationship between probiotics and ASD. Trial registration This study has been registered with Chinese Clinical Trial Registry (ChiCTR-2000037941).

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Section: Discussionmentioning

confidence: 99%

The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial

Zhang

et al. 2022

PLoS ONE

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“…Various pathologies involving neuroinflammation can result in BBB failure [ 26 , 44 , 45 , 49 , 50 , 51 , 52 , 53 , 54 ]. BBB integrity may also be affected by alterations of gut microbiota and increased gut permeability, as reported in ASD patients [ 27 , 55 ]. This dysfunction allows inflammatory mediators, bacteria, and xenobiotics to pass into the blood stream, contributing to neuroinflammation in ASD patients [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…BBB integrity may also be affected by alterations of gut microbiota and increased gut permeability, as reported in ASD patients [ 27 , 55 ]. This dysfunction allows inflammatory mediators, bacteria, and xenobiotics to pass into the blood stream, contributing to neuroinflammation in ASD patients [ 27 ]. Microbiome alterations may also be associated with gastrointestinal disturbances, frequently reported in ASD [ 28 , 55 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity

Jagadapillai

Qiu

Ojha

et al. 2022

Cells

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Autism Spectrum Disorder (ASD) is a common pediatric neurobiological disorder with up to 80% of genetic etiologies. Systems biology approaches may make it possible to test novel therapeutic strategies targeting molecular pathways to alleviate ASD symptoms. A clinical database of autism subjects was queried for individuals with a copy number variation (CNV) on microarray, Vineland, and Parent Concern Questionnaire scores. Pathway analyses of genes from pathogenic CNVs yielded 659 genes whose protein–protein interactions and mRNA expression mapped 121 genes with maximal antenatal expression in 12 brain regions. A Research Domain Criteria (RDoC)-derived neural circuits map revealed significant differences in anxiety, motor, and activities of daily living skills scores between altered CNV genes and normal microarrays subjects, involving Positive Valence (reward), Cognition (IQ), and Social Processes. Vascular signaling was identified as a biological process that may influence these neural circuits. Neuroinflammation, microglial activation, iNOS and 3-nitrotyrosine increase in the brain of Semaphorin 3F- Neuropilin 2 (Sema 3F-NRP2) KO, an ASD mouse model, agree with previous reports in the brain of ASD individuals. Signs of platelet deposition, activation, release of serotonin, and albumin leakage in ASD-relevant brain regions suggest possible blood brain barrier (BBB) deficits. Disruption of neurovascular signaling and BBB with neuroinflammation may mediate causative pathophysiology in some ASD subgroups. Although preliminary, these data demonstrate the potential for developing novel therapeutic strategies based on clinically derived data, genomics, cognitive neuroscience, and basic neuroscience methods.

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“…Also, increased intestinal permeability (“leaky gut”) in patients with ASD, potentially related to abnormal microbiome, were observed in a study showing that 43% of children with ASD compared to 0% of the controls presented an abnormal mannitol:lactulose test ( D'Eufemia et al, 19921996 ). Disrupted gut–blood–brain barriers may allow bacteria metabolites and other substances to get into the bloodstream and, subsequently, alter the brain ( Al-Ayadhi et al, 2021 ).…”

Section: Main Textmentioning

confidence: 99%

Possible Effect of the use of Mesenchymal Stromal Cells in the Treatment of Autism Spectrum Disorders: A Review

Tamouza

Volt

Richard

et al. 2022

Front. Cell Dev. Biol.

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Autism spectrum disorder (ASD) represents a set of heterogeneous neurodevelopmental conditions defined by impaired social interactions and repetitive behaviors. The number of reported cases has increased over the past decades, and ASD is now a major public health burden. So far, only treatments to alleviate symptoms are available, with still unmet need for an effective disease treatment to reduce ASD core symptoms. Genetic predisposition alone can only explain a small fraction of the ASD cases. It has been reported that environmental factors interacting with specific inter-individual genetic background may induce immune dysfunctions and contribute to the incidence of ASD. Such dysfunctions can be observed at the central level, with increased microglial cells and activation in ASD brains or in the peripheral blood, as reflected by high circulating levels of pro-inflammatory cytokines, abnormal activation of T-cell subsets, presence of auto-antibodies and of dysregulated microbiota profiles. Altogether, the dysfunction of immune processes may result from immunogenetically-determined inefficient immune responses against a given challenge followed by chronic inflammation and autoimmunity. In this context, immunomodulatory therapies might offer a valid therapeutic option. Mesenchymal stromal cells (MSC) immunoregulatory and immunosuppressive properties constitute a strong rationale for their use to improve ASD clinical symptoms. In vitro studies and pre-clinical models have shown that MSC can induce synapse formation and enhance synaptic function with consequent improvement of ASD-like symptoms in mice. In addition, two preliminary human trials based on the infusion of cord blood-derived MSC showed the safety and tolerability of the procedure in children with ASD and reported promising clinical improvement of core symptoms. We review herein the immune dysfunctions associated with ASD provided, the rationale for using MSC to treat patients with ASD and summarize the current available studies addressing this subject.

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The use of biomarkers associated with leaky gut as a diagnostic tool for early intervention in autism spectrum disorder: a systematic review

Cited by 40 publications

References 129 publications

The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial

The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial

Potential Cross Talk between Autism Risk Genes and Neurovascular Molecules: A Pilot Study on Impact of Blood Brain Barrier Integrity

Possible Effect of the use of Mesenchymal Stromal Cells in the Treatment of Autism Spectrum Disorders: A Review

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