{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:58:51Z","timestamp":1785437931411,"version":"3.56.0"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"crossref","award":["P3-0124"],"award-info":[{"award-number":["P3-0124"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"crossref","award":["J3-1756"],"award-info":[{"award-number":["J3-1756"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P3-0124"],"award-info":[{"award-number":["P3-0124"]}],"id":[{"id":"https:\/\/ror.org\/059bp8k51","id-type":"ROR","asserted-by":"publisher"}]},{"award":["J3-1756"],"award-info":[{"award-number":["J3-1756"]}],"id":[{"id":"https:\/\/ror.org\/059bp8k51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autism spectrum disorder (ASD) has been associated with alterations in the gut microbiota and its metabolites, particularly short-chain fatty acids (SCFAs) and microbiota-derived tryptophan catabolites, which may influence neurodevelopment through immune and epigenetic mechanisms. We investigated whether stool SCFAs and tryptophan-pathway metabolites differ between children with ASD and typically developing controls, and whether these metabolites associate with ASD severity and systemic biochemical signatures. In this cross-sectional study, we analyzed stool samples from 229 children (160 with ASD, 69 controls) with complete SCFA and tryptophan-metabolite data, while urine metabolomics data were available for a subset and were used for exploratory stool\u2013urine integration analyses. Children with ASD and controls were similar in age, but the ASD group had a higher proportion of males. Absolute concentrations of individual SCFAs, total SCFAs, and derived indices were broadly comparable between groups; nominal differences in propionate\/acetate ratio and caproate did not remain significant after false discovery rate correction. Similarly, stool tryptophan-pathway metabolites reported as ng\/a.u. based on the NanoDrop-derived proxy (tryptophan, kynurenine, indole-3-acetic, indole-3-lactic, indole-3-propionic, indole-3-aldehyde, N-acetyl-tryptophan, serotonin, melatonin, tryptamine) and functional ratios (kynurenine\/tryptophan, indole-derived\/tryptophan, serotonin\/tryptophan) showed no robust ASD\u2013control differences; N-acetyl-tryptophan was nominally higher in ASD but did not survive multiple-testing correction. In the ASD subgroup with available Childhood Autism Rating Scale (CARS) data (n = 34), SCFA and tryptophan indices showed only weak, non-significant correlations with global ASD severity. In contrast, correlation analyses revealed two coherent metabolic modules, i.e., an SCFA block with very strong internal correlations among individual SCFAs and total SCFAs and a tryptophan block with strong correlations between metabolites and their normalized ratios, while cross-module correlations were modest. These results indicate that stool SCFA and microbiota-derived tryptophan profiles do not robustly distinguish ASD from controls in this cohort, but they form stable metabolic modules compatible with microbiome\u2013epigenome frameworks.<\/jats:p>","DOI":"10.3390\/ijms27093988","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"3988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiome-Derived Short-Chain Fatty Acids and Tryptophan Metabolites in Children with Autism Spectrum Disorder: A Stool\u2013Urine Multi-Omics Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1839-2415","authenticated-orcid":false,"given":"Jo\u0161ko","family":"Osredkar","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Pharmacy, University of Ljubljana, A\u0161ker\u010deva 7, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7647-8882","authenticated-orcid":false,"given":"Teja","family":"Fabjan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-3435","authenticated-orcid":false,"given":"Uro\u0161","family":"Godnov","sequence":"additional","affiliation":[{"name":"The Faculty of Mathematics, Natural Sciences and Information Technologies, University of Ljubljana, Glagolja\u0161ka Ulica 8, 6000 Koper, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Jekovec-Vrhov\u0161ek","sequence":"additional","affiliation":[{"name":"Center for Autism, Unit of Child Psychiatry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-420X","authenticated-orcid":false,"given":"Damjan","family":"Osredkar","sequence":"additional","affiliation":[{"name":"Department of Child, Adolescent and Developmental Neurology, Division of Pediatrics, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, Vrazov Trg 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7857-3381","authenticated-orcid":false,"given":"Petra","family":"Finderle","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0358-4470","authenticated-orcid":false,"given":"Kristina","family":"Kumer","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Zalo\u0161ka Cesta 2, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-028X","authenticated-orcid":false,"given":"Ma\u0161a","family":"Zorec","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biotechnical Faculty, University of Ljubljana, Groblje 3, 1230 Dom\u017eale, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6800","authenticated-orcid":false,"given":"Lijana","family":"Fanedl","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biotechnical Faculty, University of Ljubljana, Groblje 3, 1230 Dom\u017eale, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8111-0460","authenticated-orcid":false,"given":"Gorazd","family":"Avgu\u0161tin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biotechnical Faculty, University of Ljubljana, Groblje 3, 1230 Dom\u017eale, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). 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