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.