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Title:Systemic uremic toxin burden in autism spectrum disorder : a stratified urinary metabolite analysis
Authors:ID Osredkar, Joško (Author)
ID Fabjan, Teja (Author)
ID Godnov, Uroš (Author)
ID Jekovec-Vrhovšek, Maja (Author)
ID Giebułtowicz, Joanna (Author)
ID Bobrowska-Korczak, Barbara (Author)
ID Avguštin, Gorazd (Author)
ID Kumer, Kristina (Author)
Files:.pdf PDF - Presentation file, download (895,54 KB)
MD5: D7E07170F1A2F7875CEF6A4EAD9A8745
 
URL URL - Source URL, visit https://www.mdpi.com/1422-0067/26/15/7070
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo UKC LJ - Ljubljana University Medical Centre
Abstract:Autism spectrum disorder (ASD) is increasingly associated with microbial and metabolic disturbances, including the altered production of gut-derived uremic toxins. We investigated urinary concentrations of five representative uremic toxins—indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in 161 children with ASD and 71 healthy controls. Toxins were measured using LC-MS/MS and were normalized to creatinine. Subgroup analyses were performed by sex, age group (2–5.9 vs. 6–17 years), and autism severity based on the Childhood Autism Rating Scale (CARS). In addition to individual concentrations, we calculated the total toxin burden, proportional contributions, and functional ratios (IS/PCS, PCS/TMAO, and IS/ADMA). While individual toxin levels did not differ significantly between groups, stratified analyses revealed that PCS was higher in girls and in severe cases of ASD, whereas IS and TMAO were reduced in younger and more severely affected children. The functional ratios shifted consistently with severity—IS/PCS declined from 1.69 in controls to 0.99 in severe cases of ASD, while PCS/TMAO increased from 12.2 to 20.5. These patterns suggest a phenolic-dominant microbial signature and an altered host–microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone.
Keywords:autism spectrum disorder, uremic toxins, p-cresyl sulfate, indoxyl sulfate, metabolomics, urinary biomarkers, gut microbiota, TMAO, ADMA
Publication status:Published
Publication version:Version of Record
Year of publishing:2025
Number of pages:14 str.
Numbering:Vol. 26, iss. 15, [article no.] 7070
PID:20.500.12556/DiRROS-28955 New window
UDC:616.896
ISSN on article:1422-0067
DOI:10.3390/ijms26157070 New window
COBISS.SI-ID:247150083 New window
Note:Nasl. z nasl. zaslona; Opis vira z dne 1. 9. 2025;
Publication date in DiRROS:14.04.2026
Views:21
Downloads:9
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
Publisher:MDPI
ISSN:1422-0067
COBISS.SI-ID:2779162 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P3-0124-2020
Name:Metabolni in prirojeni dejavniki reproduktivnega zdravja, porod III

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J3-1756-2019
Name:Okoljski in genetski dejavniki pri motnjah avtističnega spektra

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Language:Slovenian
Title:Systemic uremic toxin burden in autism spectrum disorder : a stratified urinary metabolite analysis
Keywords:uremični toksini, p-krezil sulfat, indoksil sulfat, metabolomika, urinski biomarkerji, črevesna mikrobiota, TMAO, ADMA


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