{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:41:14Z","timestamp":1780393274755,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Slovenian Research Agency","award":["P3-0124"],"award-info":[{"award-number":["P3-0124"]}]},{"name":"Slovenian Research Agency","award":["J3-1756"],"award-info":[{"award-number":["J3-1756"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)\u2014in 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\u20135.9 vs. 6\u201317 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\u2014IS\/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\u2013microbial metabolic balance in ASD. Functional toxin profiling may offer a more sensitive approach to characterizing metabolic disturbances in ASD than concentration analysis alone.<\/jats:p>","DOI":"10.3390\/ijms26157070","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T08:02:06Z","timestamp":1753257726000},"page":"7070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic Uremic Toxin Burden in Autism Spectrum Disorder: A Stratified Urinary Metabolite Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-2415","authenticated-orcid":false,"given":"Jo\u0161ko","family":"Osredkar","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teja","family":"Fabjan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-3435","authenticated-orcid":false,"given":"Uro\u0161","family":"Godnov","sequence":"additional","affiliation":[{"name":"The Faculty of Mathematics, Natural Sciences and Information Technologies, University of Ljubljana, Glagolja\u0161ka ulica 8, 6000 Koper, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Jekovec-Vrhov\u0161ek","sequence":"additional","affiliation":[{"name":"Center for Autism, Unit of Child Psychiatry, University Children\u2019s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-4453","authenticated-orcid":false,"given":"Joanna","family":"Giebu\u0142towicz","sequence":"additional","affiliation":[{"name":"Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1617-2352","authenticated-orcid":false,"given":"Barbara","family":"Bobrowska-Korczak","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Food Science, Faculty of Pharmacy with the Laboratory Medicine Division, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8111-0460","authenticated-orcid":false,"given":"Gorazd","family":"Avgu\u0161tin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biotechnical Faculty, University of Ljubljana, Groblje 3, 1230 Dom\u017eale, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0358-4470","authenticated-orcid":false,"given":"Kristina","family":"Kumer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). 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