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Keywords = 4-ethylphenyl sulfate

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15 pages, 2640 KiB  
Article
Urinary Untargeted Metabolic Profile Differentiates Children with Autism from Their Unaffected Siblings
by Anna Maria Timperio, Federica Gevi, Francesca Cucinotta, Arianna Ricciardello, Laura Turriziani, Maria Luisa Scattoni and Antonio M. Persico
Metabolites 2022, 12(9), 797; https://doi.org/10.3390/metabo12090797 - 26 Aug 2022
Cited by 15 | Viewed by 3561
Abstract
Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to [...] Read more.
Autism Spectrum Disorder (ASD) encompasses a clinical spectrum of neurodevelopmental conditions that display significant heterogeneity in etiology, symptomatology, and severity. We previously compared 30 young children with idiopathic ASD and 30 unrelated typically-developing controls, detecting an imbalance in several compounds belonging mainly to the metabolism of purines, tryptophan and other amino acids, as well as compounds derived from the intestinal flora, and reduced levels of vitamins B6, B12 and folic acid. The present study describes significant urinary metabolomic differences within 14 pairs, including one child with idiopathic ASD and his/her typically-developing sibling, tightly matched by sex and age to minimize confounding factors, allowing a more reliable identification of the metabolic fingerprint related to ASD. By using a highly sensitive, accurate and unbiased approach, suitable for ensuring broad metabolite detection coverage on human urine, and by applying multivariate statistical analysis, we largely replicate our previous results, demonstrating a significant perturbation of the purine and tryptophan pathways, and further highlight abnormalities in the “phenylalanine, tyrosine and tryptophan” pathway, essentially involving increased phenylalanine and decreased tyrosine levels, as well as enhanced concentrations of bacterial degradation products, including phenylpyruvic acid, phenylacetic acid and 4-ethylphenyl-sulfate. The outcome of these within-family contrasts consolidates and extends our previous results obtained from unrelated individuals, adding further evidence that these metabolic imbalances may be linked to ASD rather than to environmental differences between cases and controls. It further underscores the excess of some gut microbiota-derived compounds in ASD, which could have diagnostic value in a network model differentiating the metabolome of autistic and unaffected siblings. Finally, it points toward the existence of a “metabolic autism spectrum” distributed as an endophenotype, with unaffected siblings possibly displaying a metabolic profile intermediate between their autistic siblings and unrelated typically-developing controls. Full article
(This article belongs to the Special Issue Metabolomics of Autism Spectrum Disorder)
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18 pages, 678 KiB  
Article
A Diet Supplemented with Polyphenols, Prebiotics and Omega-3 Fatty Acids Modulates the Intestinal Microbiota and Improves the Profile of Metabolites Linked with Anxiety in Dogs
by Eden Ephraim, Jeffrey A. Brockman and Dennis E. Jewell
Biology 2022, 11(7), 976; https://doi.org/10.3390/biology11070976 - 28 Jun 2022
Cited by 13 | Viewed by 4878
Abstract
A nutrition-based approach was utilized to examine the effects of fish oil and a polyphenol blend (with or without tomato pomace) on the fecal microbiota and plasma/fecal metabolomes. Forty dogs, aged 5–14 years, were fed a washout food, then randomized to consume a [...] Read more.
A nutrition-based approach was utilized to examine the effects of fish oil and a polyphenol blend (with or without tomato pomace) on the fecal microbiota and plasma/fecal metabolomes. Forty dogs, aged 5–14 years, were fed a washout food, then randomized to consume a control (fish oil and polyphenol blend without tomato pomace) or test (fish oil and polyphenol blend with tomato pomace) food, then the washout food, and crossed over to consume the test or control food; each for 30 days. Several metabolites differed when comparing consumption of the washout with either the control or test foods, but few changed significantly between the test and control foods. Plasma levels of 4-ethylphenyl sulfate (4-EPS), a metabolite associated with anxiety disorders, demonstrated the largest decrease between the washout food and the control/test foods. Plasma 4-EPS levels were also significantly lower after dogs ate the test food compared with the control food. Other plasma metabolites linked with anxiety disorders were decreased following consumption of the control/test foods. Significant increases in Blautia, Parabacteroides, and Odoribacter in the fecal microbiota correlated with decreases in 4-EPS when dogs ate the control/test foods. These data indicate that foods supplemented with polyphenols and omega-3 fatty acids can modulate the gut microbiota to improve the profile of anxiety-linked metabolites. Full article
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