{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:12:58Z","timestamp":1788775978599,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006606","name":"Natural Science Foundation of Tianjin City","doi-asserted-by":"publisher","award":["24JCYBJC01770"],"award-info":[{"award-number":["24JCYBJC01770"]}],"id":[{"id":"10.13039\/501100006606","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Universities, Nankai University","award":["63261094"],"award-info":[{"award-number":["63261094"]}]},{"award":["63261094"],"award-info":[{"award-number":["63261094"]}],"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>2\u2032-Fucosyllactose (2\u2032-FL) represents a significant constituent within human milk oligosaccharides, and its benefits for intestinal health and neurodevelopment in infants and young children have been widely recognized. However, the mechanism by which 2\u2032-FL influences early-life behavioral development through the gut\u2013brain axis remains incompletely understood. In this study, we investigated the effects of neonatal 2\u2032-FL supplementation on behavioral development in Sprague-Dawley (SD) rats and explored its potential microbiota-metabolite regulatory mechanisms. After 4 consecutive weeks of oral gavage beginning on postnatal day 2, rats receiving 2\u2032-FL showed significantly increased average movement speed and central-area exploration time in the open field test. From a systemic perspective, 2\u2032-FL lowered blood diamine oxidase (DAO) and D-lactic acid (D-LA) concentrations while elevating colonic mRNA levels of tight junction protein-related genes, consequently enhancing intestinal barrier stability. In addition, 16S rRNA sequencing showed that 2\u2032-FL reshaped the gut microbiota structure and significantly enriched Lactobacillus, Bacteroides, and short-chain fatty acid (SCFA)-associated taxa represented by Lachnospiraceae_NK4A136_group. Untargeted metabolomics revealed that 2\u2032-FL induced systemic metabolic remodeling, characterized by upregulation of the bioactive metabolites dehydroepiandrosterone sulfate (DHEA-S) and deoxycholic acid (DCA), and downregulation of the glucocorticoid-related corticosterone. Western blot validation further showed higher hippocampal protein expression of postsynaptic density protein 95 (PSD95), brain-derived neurotrophic factor (BDNF), and synaptophysin in the 2\u2032-FL group, supporting enhanced synaptic plasticity-related signaling. In summary, neonatal 2\u2032-FL intervention enhanced exploratory behavior and was accompanied by increased hippocampal synaptic plasticity-related protein expression in rats, potentially through coordinated regulation of gut microbiota composition and systemic metabolism.<\/jats:p>","DOI":"10.3390\/foods15173151","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:23:37Z","timestamp":1788773017000},"page":"3151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal 2\u2032-Fucosyllactose Supplementation Modulates Exploratory Behavior and Hippocampal Synaptic Plasticity in Rats Through Gut Microbiota and Metabolic Remodeling"],"prefix":"10.3390","volume":"15","author":[{"given":"Miao","family":"Yu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3312-8831","authenticated-orcid":false,"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1613-2360","authenticated-orcid":false,"given":"Ruixin","family":"Kou","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3761-7506","authenticated-orcid":false,"given":"Bingye","family":"Xu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"}]},{"given":"Weiqian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jingmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China"},{"name":"Research Institute of Public Health, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/s41579-020-00460-0","article-title":"The gut microbiota\u2013brain axis in behaviour and brain disorders","volume":"19","author":"Morais","year":"2021","journal-title":"Nat. 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