{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:50:19Z","timestamp":1793227819176,"version":"4.5.0"},"reference-count":22,"publisher":"Baishideng Publishing Group Inc.","issue":"48","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"BACKGROUND<\/jats:p>\n Sepsis-induced intestinal injury disrupts barrier function and exacerbates systemic inflammation, contributing to high mortality.<\/jats:p>\n AIM<\/jats:p>\n To investigate the mechanism by which sphinganine protects against sepsis-induced intestinal injury, focusing on macrophage polarization and toll like receptor 2 (TLR2)\/nuclear factor kappa-B (NF-\u03baB) signaling.<\/jats:p>\n METHODS<\/jats:p>\n A cecal ligation and puncture sepsis model was established in mice (n = 20\/group). Treatments included sphinganine (15 mg\/kg) and a TLR2 agonist [fibroblast-stimulating lipopeptide-1 (FSL-1), 10 \u03bcg\/kg]. Serum markers [diamine oxidase (DAO), interleukin (IL)-1\u03b2, tumor necrosis factor (TNF)-\u03b1, IL-6] were measured by enzyme-linked immunosorbent assay. Intestinal injury and macrophage polarization [cluster of differentiation (CD) 86+ M1, CD206+ M2] were assessed via hematoxylin and eosin and immunofluorescence staining. Proteomic analysis, molecular docking, and Western blot were used to evaluate TLR2\/NF-\u03baB signaling. Data were analyzed by analysis of variance and t -test.<\/jats:p>\n RESULTS<\/jats:p>\n Sphinganine significantly reduced serum levels of DAO (P < 0.05), IL-1\u03b2, TNF-\u03b1, and IL-6 (P < 0.05), preserved intestinal crypt structure, and enhanced tight junction protein zonula occludens-1 expression. It promoted a shift from M1 (CD86+) to M2 (CD206+) macrophages. Proteomics identified TLR2 as the most differentially expressed protein, and molecular docking confirmed strong binding between sphinganine and TLR2 (-4.3 kcal\/mol). Sphinganine downregulated TLR2 and phosphorylated-NF-\u03baB p65 expression (P < 0.05), effects reversed by FSL-1. Total NF-\u03baB p65 levels remained unchanged.<\/jats:p>\n CONCLUSION<\/jats:p>\n Sphinganine protects against sepsis-induced intestinal injury by inhibiting TLR2\/NF-\u03baB signaling, modulating macrophage polarization toward the M2 phenotype, and preserving intestinal barrier integrity.<\/jats:p>","DOI":"10.3748\/wjg.v31.i48.112004","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T10:29:53Z","timestamp":1766744993000},"source":"Crossref","is-referenced-by-count":1,"title":["Sphinganine inhibits macrophage polarization and protects against sepsis-induced intestinal injury"],"prefix":"10.3748","volume":"31","author":[{"given":"Yi-Fan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Tian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Guo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bai-Yin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2060","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-021-06975-7"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.20.563296"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-019-0396-y"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11030932"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42502-0"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-020-00740-1"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/biom12111640"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57890-8"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1508893"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70553"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16199"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1620965"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011110-130327"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2025.108026"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05076-z"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14182-2"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1151728"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00079"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50341-w"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.934456"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196423"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S527764"}],"container-title":["World Journal of Gastroenterology"],"original-title":[],"link":[{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i48\/112004.htm","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i48\/112004.htm","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T10:30:03Z","timestamp":1766745003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.wjgnet.com\/1007-9327\/full\/v31\/i48\/112004.htm"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,28]]},"references-count":22,"journal-issue":{"issue":"48"},"alternative-id":["112004"],"URL":"https:\/\/doi.org\/10.3748\/wjg.v31.i48.112004","relation":{},"ISSN":["1007-9327"],"issn-type":[{"value":"1007-9327","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12,28]]}}}