{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:49:05Z","timestamp":1791964145676,"version":"4.3.4"},"reference-count":43,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>\n                    The etiology of pediatric autism spectrum disorder (ASD) has been increasingly linked to alterations in the gut\u2010brain axis, highlighting the intricate bidirectional communication between gut microbiota and central nervous system. The molecular mechanisms of this communication are poorly understood. Here we investigated whether ASD\u2010associated gut microbiota could exhibit altered inflammatory molecular outputs by integrating chemistry\u2010driven profiling of fecal lipopolysaccharides (LPS), functional bacterial proteomics, and neuroimmune cellular assays. Structural analyses revealed that LPS from non\u2010autistic healthy donors (NASD) displayed highly conserved carbohydrate and lipid A signatures dominated by hypo\u2010acylated\n                    <jats:italic>mono<\/jats:italic>\n                    \u2010phosphorylated species typically associated with immunomodulatory\n                    <jats:italic>Bacteroides<\/jats:italic>\n                    \u2010derived LPS. In contrast, LPS from ASD children exhibited increased structural heterogeneity. These molecular alterations were functionally reflected in human HMC3 microglial cells, where ASD\u2010derived fecal LPS induced stronger IL\u20106 and IL\u20108 release compared with NASD\u2010derived LPS, indicating enhanced neuroinflammatory potential. Functional proteomic profiling disclosed broadly comparable microbial compositions but marked metabolic divergence. These findings suggest that gut microbiota in ASD children are associated with a functionally heterogeneous microbial ecosystem characterized by altered immunostimulatory molecular outputs despite the absence of massive taxonomic shifts, with potential relevance for neuroimmune dysregulation.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70557","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:25:09Z","timestamp":1790702709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Heterogeneity of the Autism Spectrum Disorder\u2010Associated Gut Microbial Ecosystem Revealed by Fecal Lipopolysaccharides and Bacterial Proteomic Profiling"],"prefix":"10.1002","volume":"27","author":[{"given":"Stefania","family":"De Chiara","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Di Somma","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8746-1082","authenticated-orcid":false,"given":"Valentina","family":"Mazziotti","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Naples Italy"},{"name":"CEINGE Advanced Biotechnologies  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-7904","authenticated-orcid":false,"given":"Serena","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franca","family":"Oglio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Tammaro","sequence":"additional","affiliation":[{"name":"National Institute of Biostructure and Biosystems (INBB)  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Bravaccio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3456-7369","authenticated-orcid":false,"given":"Antonio","family":"Molinaro","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Naples Italy"},{"name":"CEINGE Advanced Biotechnologies  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-9574","authenticated-orcid":false,"given":"Roberto","family":"Berni Canani","sequence":"additional","affiliation":[{"name":"CEINGE Advanced Biotechnologies  Naples Italy"},{"name":"Department of Translational Medical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviana","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Naples Federico II  Naples Italy"},{"name":"CEINGE Advanced Biotechnologies  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-023-04292-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-022-01310-w"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01743-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03146"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-018-8032-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2026.102655"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00101.2024"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c01321"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5SC09900E"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuz002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-024-01794-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.0c00791"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2024.122833"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120040"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1266293"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2023.1271153"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2020.00855"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells14151130"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20150226"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-025-01164-7"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2025.174030"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20315"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2020.07.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1288-0"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031819"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2038"},{"key":"e_1_2_9_29_1","first-page":"2","article-title":"Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders","volume":"24","author":"Xie M.","year":"2026","journal-title":"Current Neuropharmacology"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1605-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-024-00948-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2026.1760635"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-67711-7"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2017.00111"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.635925"},{"key":"e_1_2_9_36_1","first-page":"83","volume-title":"Methods in Carbohydrate Chemistry","author":"Westphal O.","year":"1965"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2910-9_13"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.2.618"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201300062"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2581-1_12"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10482-017-0865-z"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2020.595905"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2026.1796397"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70557","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70557","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70557","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:34:09Z","timestamp":1791963249000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":43,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,14]]}},"alternative-id":["10.1002\/cbic.70557"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70557","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"assertion":[{"value":"2026-07-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70557"}}