{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T06:28:45Z","timestamp":1775024925605,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Scientific Research Fund Project of Beijing University of Chinese Medicine","award":["2024-JYB-JBZD-004"],"award-info":[{"award-number":["2024-JYB-JBZD-004"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374292"],"award-info":[{"award-number":["82374292"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vertical Development Fund of Beijing University of Chinese Medicine","award":["2023-ZXFZJJ-005"],"award-info":[{"award-number":["2023-ZXFZJJ-005"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic reprogramming has recently been recognized as related to immune disorders in ulcerative colitis (UC), but the specific metabolic pathways and genes involved remain unclear. Here, Mendelian randomization confirmed that mannose and mannonate exhibited a negative causal relationship with UC, and that the immune cell phenotype HLA DR on CD33dim HLA DR+ CD11b\u2212 mediated the effect of mannonate on UC. Bulk RNA sequencing data revealed that mannose metabolism abnormity is critical for driving the innate and acquired immune response. A well-performing diagnostic model related to mannose metabolism was constructed using SVM analysis, achieving an AUC-ROC value of 0.987 in the training set and an AUC-ROC value of 0.899 in the validation set. Single-cell analysis revealed that epithelial cells in which the mannose metabolism pathway was inactivated demonstrated increased intercell communication with myeloid cells, T cells, and B cells. In vitro experiments confirmed that KHK and AKR1B10 were suppressed under inflammatory stimulation, which may hinder mannose-related metabolism. This study elucidates the protective role of mannose metabolism in UC and provides a novel gene signature for diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/ijms26199443","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:25:59Z","timestamp":1758900359000},"page":"9443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Comprehensive Analyses Identify the Protective Role and Diagnostic Signature of Mannose Metabolism in Ulcerative Colitis"],"prefix":"10.3390","volume":"26","author":[{"given":"Yunze","family":"Liu","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"The First Clinical Medical College, Xuzhou Medical University, Xuzhou 221000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1888-3131","authenticated-orcid":false,"given":"Huizhong","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6317-2782","authenticated-orcid":false,"given":"Yixiao","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Ding","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Beijing University of Chinese Medicine, Beijing 100029, China"},{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Honap","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1001\/jama.2023.15389","article-title":"Ulcerative Colitis in Adults: A Review","volume":"330","author":"Gros","year":"2023","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1001\/jama.2023.23814","article-title":"What Is Ulcerative Colitis?","volume":"331","author":"Voelker","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Saez, A., Herrero-Fernandez, B., Gomez-Bris, R., S\u00e1nchez-Martinez, H., and Gonzalez-Granado, J.M. 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