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

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

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.

• Jezik: Angleški jezik
• Ključne besede: autism spectrum disorder, uremic toxins, p-cresyl sulfate, indoxyl sulfate, metabolomics, urinary biomarkers, gut microbiota, TMAO, ADMA
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; FMF - Fakulteta za matematiko in fiziko ; BF - Biotehniška fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: 14 str.
• Številčenje: Vol. 26, iss. 15, [article no.] 7070
• PID: 20.500.12556/RUL-175843
• UDK: 616.896
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms26157070
• COBISS.SI-ID: 247150083
• Datum objave v RUL: 11.11.2025

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: uremični toksini, p-krezil sulfat, indoksil sulfat, metabolomika, urinski biomarkerji, črevesna mikrobiota, TMAO, ADMA, motnja avtističnega spektra

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0124
• Naslov: Metabolni in prirojeni dejavniki reproduktivnega zdravja, porod III

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: J3-1756
• Naslov: Okoljski in genetski dejavniki pri motnjah avtističnega spektra