{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:54:19Z","timestamp":1785412459222,"version":"3.56.0"},"reference-count":73,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82560639"],"award-info":[{"award-number":["82560639"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82560639"],"award-info":[{"award-number":["82560639"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Key Project of Natural Science Foundation of Jiangxi Province","award":["20252BAC250147"],"award-info":[{"award-number":["20252BAC250147"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>This study focuses on Lacto-N-neotetraose (LNnT), a core component of human milk oligosaccharides. Although LNnT has been demonstrated to promote early intestinal development and maintain gut homeostasis, its protective mechanism against D-galactose-induced intestinal injury and associated cognitive impairment remains unclear. This investigation systematically examined the protective effects and underlying mechanisms of LNnT against D-gal-induced colonic damage and cognitive impairment in mice. The results demonstrated that LNnT not only significantly improved systemic physiological phenotypes and upregulated the expression of colonic tight junction proteins to repair the intestinal barrier, but also effectively enhanced learning and memory abilities in mice. Concurrently, LNnT reduced serum proinflammatory factor levels, elevated the anti-inflammatory factor IL-10, and alleviated oxidative stress. Furthermore, LNnT remodeled the gut microbiome structure by increasing microbial diversity, enhancing beneficial bacteria abundance, and promoting short-chain fatty acid production. Untargeted metabolomics analysis further revealed that LNnT corrected metabolic disturbances by regulating key sphingolipid molecules (ceramide, sphingosine, S1P) and the expression of related metabolic enzymes (ACER2, SphK2). In summary, this study suggests that LNnT mitigates intestinal injury and improves cognitive function, potentially through modulation of the gut microbiota\u2013sphingolipid metabolism axis, although further causal validation is warranted. These findings provide a mechanistic foundation for future studies exploring its potential as a functional dietary ingredient.<\/jats:p>","DOI":"10.3390\/molecules31091410","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:29:11Z","timestamp":1777033751000},"page":"1410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Human Milk Oligosaccharide LNnT Attenuates Colonic Barrier Dysfunction and Associated Cognitive Impairment via Modulating Sphingolipid Metabolism and Gut Microbiota"],"prefix":"10.3390","volume":"31","author":[{"given":"Minghui","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo 315010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiang","family":"Liao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Bao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-7554","authenticated-orcid":false,"given":"Hongyan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"},{"name":"International Institute of Food Innovation, Nanchang University, Nanchang 330051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-1507","authenticated-orcid":false,"given":"Zeyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"},{"name":"International Institute of Food Innovation, Nanchang University, Nanchang 330051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"},{"name":"International Institute of Food Innovation, Nanchang University, Nanchang 330051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-2653","authenticated-orcid":false,"given":"Liufeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"},{"name":"International Institute of Food Innovation, Nanchang University, Nanchang 330051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"},{"name":"International Institute of Food Innovation, Nanchang University, Nanchang 330051, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"O\u2019Callaghan, A.A., and Corr, S.C. 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