Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder
Abstract Background Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field’s understanding of ASD pathogenies and targets for early diagnosis and intervention. We the...
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BMC
2025-03-01
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| Series: | Journal of Neurodevelopmental Disorders |
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| Online Access: | https://doi.org/10.1186/s11689-025-09601-z |
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| author | Serena B. Gumusoglu Brandon M. Schickling Donna A. Santillan Lynn M. Teesch Mark K. Santillan |
| author_facet | Serena B. Gumusoglu Brandon M. Schickling Donna A. Santillan Lynn M. Teesch Mark K. Santillan |
| author_sort | Serena B. Gumusoglu |
| collection | DOAJ |
| description | Abstract Background Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field’s understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. Methods Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). Results We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612–0.896) for ASD prediction. Conclusions Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD’s earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms. |
| format | Article |
| id | doaj-art-386a9d094def4e6e8af1fb7f4d52cf00 |
| institution | OA Journals |
| issn | 1866-1955 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj-art-386a9d094def4e6e8af1fb7f4d52cf002025-08-20T02:10:09ZengBMCJournal of Neurodevelopmental Disorders1866-19552025-03-0117111010.1186/s11689-025-09601-zDisrupted fetal carbohydrate metabolism in children with autism spectrum disorderSerena B. Gumusoglu0Brandon M. Schickling1Donna A. Santillan2Lynn M. Teesch3Mark K. Santillan4Department of Obstetrics and Gynecology, University of IowaDepartment of Obstetrics and Gynecology, University of IowaDepartment of Obstetrics and Gynecology, University of IowaDepartment of Chemistry, University of IowaDepartment of Obstetrics and Gynecology, University of IowaAbstract Background Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field’s understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. Methods Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). Results We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612–0.896) for ASD prediction. Conclusions Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD’s earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms.https://doi.org/10.1186/s11689-025-09601-zAutismMetabolomicsCarbohydratesMonosaccharidesPolysaccharidesCord blood |
| spellingShingle | Serena B. Gumusoglu Brandon M. Schickling Donna A. Santillan Lynn M. Teesch Mark K. Santillan Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder Journal of Neurodevelopmental Disorders Autism Metabolomics Carbohydrates Monosaccharides Polysaccharides Cord blood |
| title | Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| title_full | Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| title_fullStr | Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| title_full_unstemmed | Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| title_short | Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| title_sort | disrupted fetal carbohydrate metabolism in children with autism spectrum disorder |
| topic | Autism Metabolomics Carbohydrates Monosaccharides Polysaccharides Cord blood |
| url | https://doi.org/10.1186/s11689-025-09601-z |
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