20.500.12556/DiRROS-28957 Urinary uremic toxin signatures and the metabolic index of gut dysfunction (MIGD) in autism spectrum disorder a stool-phenotype-stratified analysis Gut-derived uremic toxins may play a key role in neurodevelopmental conditions such as autism spectrum disorder (ASD) via host-microbe metabolic interactions. We evaluated five uremic toxins—p-cresyl sulfate (PCS), indoxyl sulfate (IS), trimethylamine N-oxide (TMAO), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)—in urine samples of 97 children with ASD and 71 neurotypical controls, stratified by Bristol Stool Chart (BSC) consistency types. Four of these toxins (PCS, IS, TMAO, ADMA) were integrated into a novel composite biomarker called the Metabolic Index of Gut Dysfunction (MIGD), while SDMA was measured as a complementary renal function marker. While individual metabolite levels showed no statistically significant differences, group-wise analysis by stool phenotype revealed distinct trends. ASD children with hard stools (BSC 1–2) showed elevated PCS levels and the MIGD score (median 555.3), reflecting phenolic fermentation dominance with reduced indolic detoxification. In contrast, children with loose stools (BSC 6–7) had the lowest MIGD values (median 109.8), driven by higher IS and lower ADMA concentrations, suggestive of enhanced indole metabolism. These findings indicate that MIGD may serve as a novel biomarker to stratify metabolic phenotypes in ASD, linking urinary metabolite patterns to gut function. Further validation in larger and longitudinal cohorts is warranted to confirm its potential utility in precision microbiota-targeted interventions. autism spectrum disorder uremic toxins microbiota–host interactions p-cresyl sulfate indoxyl sulfate gut metabolic dysfunction urinary biomarkers Bristol stool chart uremični toksini interakcije med mikrobioto in gostiteljem p-krezil sulfat indoksil sulfat presnovna disfunkcija črevesja biomarkerji urina Bristolska tabela blata true false true Angleški jezik Slovenski jezik Neznano 2026-04-14 14:46:36 2026-04-14 14:46:37 2026-04-15 03:57:41 0000-00-00 00:00:00 2025 0 0 Nasl. z nasl. zaslona; Opis vira z dne 17. 11. 2025; 14 str. iss. 21, [article no.] 10475 Vol. 26 Sep. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.896 1422-0067 10.3390/ijms262110475 257431043 RAZ_Osredkar_Josko_2025.pdf RAZ_Osredkar_Josko_2025.pdf 1 1A5256B0BECD34ABB0E383F3541ED824 ca0dca14f4516730eb703690c8c64af297449be34b5dd193c0fcd564e0e68215 18906bd4-3800-11f1-9cc3-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43199 https://www.mdpi.com/1422-0067/26/21/10475 1 fbaa8cd3-37ff-11f1-9cc3-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43198 Univerzitetni klinični center Ljubljana 0 0 0