{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:23:16Z","timestamp":1793744596470,"version":"4.6.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Children with autism spectrum disorder (ASD) commonly exhibit gut microbiota dysbiosis and metabolic abnormalities, yet the mechanisms linking these changes to clinical symptoms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study employed a nested case\u2013control design and multi-omics approaches to evaluate the effects of rehabilitation intervention on clinical symptoms and gut microbiota in children with ASD, identify distinct microbial-metabolic signatures, and explore their mechanistic links with sleep disorders and developmental abilities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Within a prospectively established pediatric cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f45), we implemented a nested case\u2013control design including 26 ASD children (18 males, 8 females; mean age 61.79\u202f\u00b1\u202f11.15\u202fmonths) and 19 age- and sex-matched healthy controls. All ASD participants received standardized rehabilitation therapy (2\u202fh\/day, 5\u202fdays\/week for 6\u202fmonths) comprising occupational therapy and cognitive-linguistic training. Primary outcomes included comprehensive clinical assessments [Griffiths Development Scales-Chinese (GDS-C), Children\u2019s Sleep Habits Questionnaire (CSHQ), Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS)] and longitudinal multi-omics analysis (metagenomic sequencing and LC\u2013MS-based metabolomics). Association analyses were performed with FDR correction (\n                      <jats:italic>q<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following the 6-month rehabilitation intervention, significant clinical improvements were observed in sleep quality (CSHQ total and subscores) and developmental performance (GDS-C). Multi-omics profiling revealed distinct biological signatures in ASD children compared to healthy controls, characterized by elevated\n                      <jats:italic>Intestinibacter_bartlettii<\/jats:italic>\n                      and reduced levels of ornithine and siderophore nonribosomal peptide biosynthesis. Crucially, correlation analysis demonstrated that, after FDR correction, ornithine levels were significantly positively correlated with multiple GDS-C developmental domains, while tyrosine was associated with parasomnias. These findings establish a potential mechanistic link where amino acid metabolism connects gut microbial shifts to clinical phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates that rehabilitation intervention synchronously ameliorates clinical symptoms and modulates the gut-metabolic profile in ASD. The identified associations between specific metabolites (ornithine and tyrosine) and clinical outcomes suggest a metabolic mechanism underlying the gut-brain axis, highlighting the potential of these metabolites as biomarkers for therapeutic monitoring. Further large-scale studies are needed to validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1820904","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:33:59Z","timestamp":1780896839000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiome dynamics in autism: a prospective nested case\u2013control study demonstrates microbial-clinical associations following rehabilitation interventions"],"prefix":"10.3389","volume":"20","author":[{"given":"Juanjuan","family":"Chen","sequence":"first","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinying","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Germplasm Innovation and Utilization of Specialty Commercial Crops in North Guangxi, Guangxi Academy of Specialty Crops","place":["Guilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Pediatrics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,8]]},"reference":[{"key":"ref1","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2013"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3389\/fcimb.2020.00223","article-title":"Gut microbiota dysbiosis associated with altered production of short chain fatty acids in children with neurodevelopmental disorders","volume":"10","author":"Bojovic","year":"2020","journal-title":"Front. 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