Systemic uremic toxin burden in autism spectrum disorder : a stratified urinary metabolite analysis

Osredkar, Joško (author), Fabjan, Teja (author), Godnov, Uroš (author), Jekovec-Vrhovšek, Maja (author), Giebułtowicz, Joanna (author), Bobrowska-Korczak, Barbara (author), Avguštin, Gorazd (author), Kumer, Kristina (author)

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.

• Language: English
• Keywords: autism spectrum disorder, uremic toxins, p-cresyl sulfate, indoxyl sulfate, metabolomics, urinary biomarkers, gut microbiota, TMAO, ADMA
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; FMF - Faculty of Mathematics and Physics; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 14 str.
• Numbering: Vol. 26, iss. 15, [article no.] 7070
• PID: 20.500.12556/RUL-175843
• UDC: 616.896
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms26157070
• COBISS.SI-ID: 247150083
• Publication date in RUL: 11.11.2025

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

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
• Keywords: uremični toksini, p-krezil sulfat, indoksil sulfat, metabolomika, urinski biomarkerji, črevesna mikrobiota, TMAO, ADMA, motnja avtističnega spektra

Projects

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

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