Measurement of urine indolylacroylglycine is not useful in the diagnosis or dietary management of autism

Abstract

Lay AbstractIncreased urinary excretion of indolylacroylglycine (IAG) has been proposed as a useful biomarker for the diagnosis and dietary management of patients with autism spectrum disorder (ASD). It has been suggested that this may be due to abnormal metabolism of tryptophan and/or evidence of increased gut permeability to peptides, and may be a valuable biomarker of a process underlying autism viz. the hypothesis that ASD could be caused by increased gut absorption of neuroactive peptides, derived from gluten in wheat and casein in milk, harmful to the brain. This hypothesis has supported the use of gluten-and casein-free diets in those with ASD, and testing of urine for IAG as a prelude to advising dietary manipulation in individuals with ASD. However, there are conflicting reports of whether or not people with ASD have increased amounts of IAG in their urine, the fundamental finding on which the hypothesis above is built. One recent study found increased IAG in the urine of children with persistent gastrointestinal problems. The present study compares IAG in the urine in children with ASD, children with special needs, and in typically developing children and finds no difference among the groups. Neither was there any difference in those with and without current gastrointestinal problems. We found no evidence of increased IAG excretion or for any link to abnormal tryptophan metabolism and/or gut permeability in children with ASD. The data suggest that the measurement of urinary IAG has no value in the diagnosis of ASD or in the dietary management of patients with ASD. 3 Scientific abstractObjective. To measure urine indolylacroylglycine (IAG) excretion using the IAG:creatinine ratio in children with autism spectrum disorder (ASD) compared with two groups of age matched controls, one with special needs but without ASD (SEN) and one typically developing (TD) and in subgroups with/without current gastrointestinal problems and ASD with and without regression.Participants and methods. IAG:creatinine ratio was measured in the urine of 279 children aged 10-14 years: 129 children with ASD (28 with and 101 without regression), 62 SEN controls and 88 TD controls. The prevalence of gastro-intestinal symptoms (GIS) was recorded.Results. No differences were found in the urine IAG:creatinine ratio among groups ASD, TD and SEN; nor in the ASD groups with/without regression, nor in those with/without GIS.Conclusions. This study finds no evidence of increased urine IAG excretion in children with ASD, with or without GIS or with or without regression. Urinary IAG measurements in children with ASD offer no support for increased presence of neuroactive peptides proposed to result from increased gut permeability. We found measurement of urinary IAG to have no value in the diagnosis of autism or in the dietary management of children with ASD.

Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers

“…IAcrGly is one of the physiological components in urine. It was hypothesized that abnormal gut flora could promote the conversion of tryptophan to indolyl propionic acid, which could cause an increased IAcrGly level in urine 58 , 59 . The trans-verse situation might be true for patients with bladder or CRC.…”

Potential role of Lactobacillus plantarum in colitis induced by dextran sulfate sodium through altering gut microbiota and host metabolism in murine model

“…Moreover, studies have shown that anti-inflammatory 13-oxoODE can inhibit the secretion of TNF-α by macrophages stimulated by EC, and this process can be reversed by PPARγ antagonist GW9662 (Ryman et al, 2016;Wysoczanski et al, 2019). While urinary indolylacroylglycine levels are elevated in ASD children, inconsistent results have been reported elsewhere in the literature (Dalton et al, 2017). The reduction of Bacteroidetes may weaken the immune tolerance of intestinal microbe (Jalanka et al, 2020).…”