| Title: | Altered stool cytokine profiles and pro-onflammatory/anti-inflammatory imbalance in children with autism spectrum disorder : a developmental analysis |
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| Authors: | ID Finderle, Petra (Author)
ID Jekovec-Vrhovšek, Maja (Author)
ID Prosenc Zmrzljak, Uršula (Author)
ID Osredkar, Damjan (Author)
ID Avguštin, Gorazd (Author)
ID Osredkar, Joško (Author) |
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| Files: |  PDF - Presentation file, download (1,62 MB)
MD5: FEDF497A825EA2429CD8490A1D967C30
 URL - Source URL, visit https://www.mdpi.com/2227-9059/14/7/1559
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | 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. |
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| Keywords: | autism spectrum disorder, cytokines, stool biomarkers, IL-8, IL-4, interleukin, gut–immune axis, CARS, developmental immunology |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 1-24 |
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| Numbering: | Vol. 14, issue 7, [article no.] 1559 |
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| PID: | 20.500.12556/DiRROS-31654  |
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| UDC: | 616.896+616-097 |
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| ISSN on article: | 2227-9059 |
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| DOI: | 10.3390/biomedicines14071559 |
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| COBISS.SI-ID: | 286211331 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 28. 7. 2026;
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| Publication date in DiRROS: | 06.08.2026 |
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| Views: | 16 |
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| Downloads: | 13 |
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