20.500.12556/DiRROS-28955 Systemic uremic toxin burden in autism spectrum disorder a stratified urinary metabolite analysis Systemic uremic toxin burden in autism spectrum disorder : a stratified urinary metabolite analysis 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. autism spectrum disorder uremic toxins p-cresyl sulfate indoxyl sulfate metabolomics urinary biomarkers gut microbiota TMAO ADMA uremični toksini p-krezil sulfat indoksil sulfat metabolomika urinski biomarkerji črevesna mikrobiota TMAO ADMA true false true Angleški jezik Slovenski jezik Neznano 2026-04-14 14:33:41 2026-04-14 14:33:41 2026-04-15 03:57:41 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 1. 9. 2025; 14 str. iss. 15, [article no.] 7070 Vol. 26 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.896 1422-0067 10.3390/ijms26157070 247150083 RAZ_Osredkar_Josko_2025.pdf RAZ_Osredkar_Josko_2025.pdf 1 D7E07170F1A2F7875CEF6A4EAD9A8745 99bcfd2926a9c8e1e576018485cec5595e4aa6af9cbda966e90abf8d3e7f210d 41c5b83c-37fe-11f1-9cc3-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43194 https://www.mdpi.com/1422-0067/26/15/7070 1 2d9e45ee-37fe-11f1-9cc3-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43193 Univerzitetni klinični center Ljubljana 0 0 0