Identification of indolyl-3-acryloylglycine in the urine of people with autism

Anderson, Rosaleen J.; Bendell, David J.; Garnett, Ian; Groundwater, Paul W.; Lough, W. J.; Mills, Malcolm J.; Savery, Dawn; Shattock, Paul

doi:10.1211/0022357021778349

Cited by 23 publications

(26 citation statements)

References 12 publications

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“…Specimens were prepared and analysed blind and independently by highperformance liquid chromatography (HPLC) with UV diode-array detection (DAD) according to established protocols. [32][33][34][35] Analysis on urine fractions was executed for compounds co-eluting with exogenous opioid peptide standards and/or trans-indolyl-3-acryloylglycine (IAG).…”

Section: Methodsmentioning

confidence: 99%

The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders

Whiteley

Haracopos²,

Knivsberg

et al. 2010

Nutritional Neuroscience

212

165

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There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomisation. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) to determine inattention and hyperactivity. Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment. Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention. The study was registered with ClincialTrials.gov, number NCT00614198.

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Section: Methodsmentioning

confidence: 99%

The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders

Whiteley

Haracopos²,

Knivsberg

et al. 2010

Nutritional Neuroscience

212

165

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“…IAG is a regular constituent of human urine and is produced by gut microflora (54,55) . It has been speculated that high levels of IAG in urine are an indication of gut dysbiosis (56) .…”

Section: Indolylacryloylglycinementioning

confidence: 99%

“…It has been speculated that high levels of IAG in urine are an indication of gut dysbiosis (56) . A few studies found increased levels of IAG in autistic individuals compared with asymptomatic controls (54,55) . Normally, tryptophan is catabolised to indole pyruvate and indole acetate and can be detected in the urine of normal subjects (57) .…”

Section: Indolylacryloylglycinementioning

confidence: 99%

Autism and nutrition: the role of the gut–brain axis

2014

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Autism spectrum disorder (ASD) is characterised by deficits in the ability to socialise, communicate and use imagination, and displays of stereotypical behaviour. It is widely accepted that ASD involves a disorder in brain development. However, the real causes of the neurodevelopmental disorders associated with ASD are not clear. In this respect, it has been found that a majority of children with ASD display gastrointestinal symptoms, and an increased intestinal permeability. Moreover, large differences in microbiotic composition between ASD patients and controls have been reported. Therefore, nutrition-related factors have been hypothesised to play a causal role in the aetiology of ASD and its symptoms. Through a review of the literature, it was found that abnormalities in carbohydrate digestion and absorption could explain some of the gastrointestinal problems observed in a subset of ASD patients, although their role in the neurological and behavioural problems remains uncertain. In addition, the relationship between an improved gut health and a reduction of symptoms in some patients was evaluated. Recent trials involving gluten-free diets, casein-free diets, and pre-and probiotic, and multivitamin supplementation show contradictive but promising results. It can be concluded that nutrition and other environmental influences might trigger an unstable base of genetic predisposition, which may lead to the development of autism, at least in a subset of ASD patients. Clear directions for further research to improve diagnosis and treatment for the different subsets of the disorder are provided.

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“…In the context of proposed bowel and metabolism problems in autism some have suggested that the metabolite, indolyl-3-acryloylglycine (IAG), has been found in the urine of children with ASD, and may be a putative marker for autism and tryptophan metabolism problems (27). However, this study had no comparison to a control group to establish its specificity to the disorder.…”

Section: Introductionmentioning

confidence: 85%