20.500.12556/DiRROS-31654 Altered stool cytokine profiles and pro-onflammatory/anti-inflammatory imbalance in children with autism spectrum disorder a developmental analysis Background: Immune dysregulation and gut dysbiosis are increasingly implicated in autism spectrum disorder (ASD), but compartment-specific intestinal cytokine profiles remain poorly defined. Aim: To characterize stool cytokine profiles and pro-/anti-inflammatory balance in children with ASD across development. Methods: We analyzed stool samples from 283 children (109 controls, 104 mild ASD, 70 severe ASD; age 0.9–21.5 years) recruited at a tertiary centre. Nine cytokines (IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, TNF-α) were measured using a Luminex multi-plex assay; IL-15 was excluded due to >70% missing values. Group comparisons used Mann–Whitney U tests, with age stratification at the cohort median (≤9.5 vs. >9.5 years). A composite pro-/anti-inflammatory ratio (IL-1α + IL-1β + IL-6 + IL-8 + IL-17 + TNF-α + IFN-γ divided by IL-4 + IL-10) was calculated. Results: In the overall cohort, stool IL-8 and IL-4 were significantly decreased in ASD versus controls (IL-8: median 0.36 vs. 0.49 ng/L, p = 0.0041; IL-4: 0.28 vs. 0.30 ng/L, p = 0.0316), with a graded reduction from controls to mild and severe ASD. Age-stratified analysis revealed that IL-8 reduction was confined to younger children (≤9.5 years; p = 0.0025) and absent in older children, while IL-1β was significantly reduced in younger ASD children and tended to reverse in older ASD children. The pro-/anti-inflammatory ratio was markedly elevated in severe ASD (median 491 vs. 209 in controls; p = 0.059), particularly in older children. Stool IL-8 and IL-1β correlated inversely with CARS scores within the ASD group. Conclusions: Children with ASD show decreased stool IL-8 and IL-4 and a shift toward a pro-inflammatory cytokine balance, with the strongest alterations during early childhood. These findings are consistent with the hypothesis of a developmental window of intestinal immune dysregulation in ASD, with stool IL-8 as the primary FDR-corrected finding. The present cross-sectional data do not establish causality and independent replication is required before clinical conclusions are drawn. autism spectrum disorder cytokines stool biomarkers IL-8 IL-4 interleukin gut–immune axis CARS developmental immunology biomarkerji v blatu IL-8 IL-4 interlevkin črevesno-imunska os CARS razvojna imunologija true false true Angleški jezik Slovenski jezik Neznano 2026-08-06 08:43:46 2026-08-06 08:43:47 2026-08-07 03:58:25 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 28. 7. 2026; str. 1-24 issue 7, [article no.] 1559 Vol. 14 Jul. 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.896+616-097 2227-9059 10.3390/biomedicines14071559 286211331 RAZ_Finderle_Petra_2026.pdf RAZ_Finderle_Petra_2026.pdf 1 FEDF497A825EA2429CD8490A1D967C30 dc25c53b087dee1ece18be55f3302bb1b8aa97515e3acc6f90ce86480179270e 53500453-9162-11f1-af5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=49110 https://www.mdpi.com/2227-9059/14/7/1559 1 2e0cf75b-9162-11f1-af5a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=49109 Univerzitetni klinični center Ljubljana 0 0 0