{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:23:52Z","timestamp":1787743432017,"version":"build-2784847793"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":96,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colonic mucosa. Changes in mucin phenotype may be associated with mucosal inflammation in UC. However, the relationship between clinicopathological features and mucus phenotypes in UC remains unclear. Therefore, we aimed to evaluate the association between mucus phenotypes and clinicopathological features in patients with UC using immunohistochemistry, as well as their association with ultra-high magnification endocytoscopy (EC) classification. A total of 51 lower gastrointestinal endocytoscopy procedures were performed for 39 patients with UC between 2018 and 2022. MUC2 expression was positive in all biopsy specimens, whereas MUC1, MUC6, and CD10 expression was negative. MUC5AC was expressed in 51.3% of cases. MUC5AC positivity was associated with duration of disease, classification by clinical course, Mayo score, Mayo endoscopic subscore (MES), Nancy histological index, C-reactive protein levels, erythrocyte sedimentation rate, and EC classification at the patient level. At the specimen level, significant differences were observed in the Nancy histological index, MES, and EC classification. In multivariate analysis, the Nancy histological index showed a significant correlation.MUC5AC is strongly correlated with histopathological severity and may also be associated with clinical and endoscopic severity. The clinical significance of MUC5AC positivity remains a topic for future investigation.<\/jats:p>","DOI":"10.1038\/s41598-026-53592-3","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T03:08:21Z","timestamp":1779419301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between mucus phenotypes, histopathological features, and ultra-high magnification endoscopic findings in ulcerative colitis"],"prefix":"10.1038","volume":"16","author":[{"given":"Takeshi","family":"Hashimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kurumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shungo","family":"Kanetsuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Kanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Ikebuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Yashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Sakabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Umekita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Isomoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"53592_CR1","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1038\/ajg.2010.281","volume":"105","author":"CW Png","year":"2010","unstructured":"Png, C. W. et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am. J. Gastroenterol. 105, 2420\u20132428. https:\/\/doi.org\/10.1038\/ajg.2010.281 (2010).","journal-title":"Am. J. Gastroenterol."},{"key":"53592_CR2","doi-asserted-by":"publisher","unstructured":"Verstockt, B., Bressler, B., Martinez-Lozano, H., McGovern, D. & Silverberg, M. S. Time to revisit disease classification in inflammatory bowel disease: Is the current classification of inflammatory bowel disease good enough for optimal clinical management? Gastroenterology 162, 1370\u20131382. https:\/\/doi.org\/10.1053\/j.gastro.2021.12.246 (2022).","DOI":"10.1053\/j.gastro.2021.12.246"},{"key":"53592_CR3","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1016\/j.cgh.2020.01.028","volume":"18","author":"AN Ananthakrishnan","year":"2020","unstructured":"Ananthakrishnan, A. N., Kaplan, G. G. & Ng, S. C. Changing global epidemiology of inflammatory bowel diseases: Sustaining health care delivery into the 21st century. Clin. Gastroenterol. Hepatol. 18, 1252\u20131260. https:\/\/doi.org\/10.1016\/j.cgh.2020.01.028 (2020).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"53592_CR4","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.3390\/jcm10091935","volume":"10","author":"E Bankole","year":"2021","unstructured":"Bankole, E., Read, E., Curtis, M. A., Neves, J. F. & Garnett, J. A. The relationship between mucins and ulcerative colitis: A systematic review. J. Clin. Med. 10, 1935. https:\/\/doi.org\/10.3390\/jcm10091935 (2021).","journal-title":"J. Clin. Med."},{"key":"53592_CR5","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1136\/gut.38.4.554","volume":"38","author":"KM Tytgat","year":"1996","unstructured":"Tytgat, K. M., Opdam, F. J., Einerhand, A. W., B\u00fcller, H. A. & Dekker, J. MUC2 is the prominent colonic mucin expressed in ulcerative colitis. Gut 38, 554\u2013563. https:\/\/doi.org\/10.1136\/gut.38.4.554 (1996).","journal-title":"Gut"},{"key":"53592_CR6","doi-asserted-by":"publisher","unstructured":"Dorofeyev, A. E., Vasilenko, I. V., Rassokhina, O. A. & Kondratiuk, R. B. Mucosal barrier in ulcerative colitis and Crohn\u2019s disease. Gastroenterol. Res. Pract. 2013, 431231. https:\/\/doi.org\/10.1155\/2013\/431231 (2013).","DOI":"10.1155\/2013\/431231"},{"key":"53592_CR7","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1248\/bpb.b12-00412","volume":"35","author":"H Kawashima","year":"2012","unstructured":"Kawashima, H. Roles of the gel-forming MUC2 mucin and its O-glycosylation in the protection against colitis and colorectal cancer. Biol. Pharm. Bull. 35, 1637\u20131641. https:\/\/doi.org\/10.1248\/bpb.b12-00412 (2012).","journal-title":"Biol. Pharm. Bull."},{"key":"53592_CR8","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1002\/ijc.22865","volume":"121","author":"ME Forgue-Lafitte","year":"2007","unstructured":"Forgue-Lafitte, M. E. et al. Abnormal expression of M1\/MUC5AC mucin in distal colon of patients with diverticulitis, ulcerative colitis and cancer. Int. J. Cancer 121, 1543\u20131549. https:\/\/doi.org\/10.1002\/ijc.22865 (2007).","journal-title":"Int. J. Cancer"},{"key":"53592_CR9","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1007\/s00428-006-0188-3","volume":"448","author":"N Tatsumi","year":"2006","unstructured":"Tatsumi, N. et al. Cytokeratin 7\/20 and mucin core proteion expression in ulcerative colitis-associated colorectal neoplasms. Virchows Arch. 448, 756\u2013762. https:\/\/doi.org\/10.1007\/s00428-006-0188-3 (2006).","journal-title":"Virchows Arch."},{"key":"53592_CR10","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1019\/ecco-jcc\/jjy","volume":"12","author":"R Ozaki","year":"2018","unstructured":"Ozaki, R. et al. Histological risk factors to predict relapse in ulcerative colitis with endoscopically normal mucosa. J. Crohns Colitis 12, 1288\u20131294. https:\/\/doi.org\/10.1019\/ecco-jcc\/jjy (2018).","journal-title":"J. Crohns Colitis"},{"key":"53592_CR11","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1007\/s00535-022-01924-1","volume":"57","author":"J Ohara","year":"2022","unstructured":"Ohara, J. et al. Deep learning-based automated quantification of goblet cell mucus using histological images as a predictor of clinical relapse of ulcerative colitis with endoscopic remission. J. Gastroenterol. 57, 962\u2013970. https:\/\/doi.org\/10.1007\/s00535-022-01924-1 (2022).","journal-title":"J. Gastroenterol."},{"key":"53592_CR12","doi-asserted-by":"publisher","first-page":"e0107","DOI":"10.1097\/MD.0000000000010107","volume":"97","author":"N Ueda","year":"2018","unstructured":"Ueda, N. et al. Endocytoscopic classification can be predictive for relapse in ulcerative colitis. Medicine 97, e0107. https:\/\/doi.org\/10.1097\/MD.0000000000010107 (2018).","journal-title":"Medicine"},{"key":"53592_CR13","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/ajg.2009.727","volume":"105","author":"A Kornbluth","year":"2010","unstructured":"Kornbluth, A., Sachar, D. B. & Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, practice parameters committee. Am. J. Gastroenterol. 105, 501\u2013523. https:\/\/doi.org\/10.1038\/ajg.2009.727 (2010). quiz 524.","journal-title":"Am. J. Gastroenterol."},{"key":"53592_CR14","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1056\/NEJM198712243172603","volume":"317","author":"KW Schroeder","year":"1987","unstructured":"Schroeder, K. W., Tremaine, W. J. & Ilstrup, D. M. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl. J. Med. 317, 1625\u20131629. https:\/\/doi.org\/10.1056\/NEJM198712243172603 (1987).","journal-title":"N Engl. J. Med."},{"key":"53592_CR15","doi-asserted-by":"publisher","first-page":"5A","DOI":"10.1155\/2005\/269076","volume":"19","author":"MS Silverberg","year":"2005","unstructured":"Silverberg, M. S. et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can. J. Gastroenterol. 19, 5A\u201336A. https:\/\/doi.org\/10.1155\/2005\/269076 (2005).","journal-title":"Can. J. Gastroenterol."},{"key":"53592_CR16","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00535-021-01784-1","volume":"56","author":"H Nakase","year":"2021","unstructured":"Nakase, H. et al. Evidence-based clinical practice guidelines for inflammatory bowel disease 2020. J. Gastroenterol. 56, 489\u2013526. https:\/\/doi.org\/10.1007\/s00535-021-01784-1 (2021).","journal-title":"J. Gastroenterol."},{"key":"53592_CR17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1136\/gutjnl-2015-310187","volume":"66","author":"A Marchal-Bressenot","year":"2017","unstructured":"Marchal-Bressenot, A. et al. Development and validation of the Nancy histological index for UC. Gut 66, 43\u201349. https:\/\/doi.org\/10.1136\/gutjnl-2015-310187 (2017).","journal-title":"Gut"},{"key":"53592_CR18","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.crohns.2007.06.006","volume":"1","author":"P Borralho","year":"2007","unstructured":"Borralho, P., Vieira, A., Freitas, J., Chaves, P. & Soares, J. Aberrant gastric apomucin expression in ulcerative colitis and associated neoplasia. J. Crohns Colitis 1, 35\u201340. https:\/\/doi.org\/10.1016\/j.crohns.2007.06.006 (2007).","journal-title":"J. Crohns Colitis"},{"key":"53592_CR19","doi-asserted-by":"publisher","first-page":"103751","DOI":"10.1016\/j.ebiom.2021.103751","volume":"74","author":"D Yao","year":"2021","unstructured":"Yao, D., Dai, W., Dong, M., Dai, C. & Wu, S. MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis. EBiomedicine 74, 103751. https:\/\/doi.org\/10.1016\/j.ebiom.2021.103751 (2021).","journal-title":"EBiomedicine"},{"key":"53592_CR20","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1136\/gut.35.3.353","volume":"35","author":"RD Pullan","year":"1994","unstructured":"Pullan, R. D. et al. Thickness of adherent mucus gel on colonic mucosa in humans and its relevance to colitis. Gut 35, 353\u2013359. https:\/\/doi.org\/10.1136\/gut.35.3.353 (1994).","journal-title":"Gut"},{"key":"53592_CR21","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3390\/ijms17040578","volume":"17","author":"M Matija\u0161i\u0107","year":"2016","unstructured":"Matija\u0161i\u0107, M. et al. Modulating composition and metabolic activity of the gut microbiota in ibd patients. Int. J. Mol. Sci. 17, 578. https:\/\/doi.org\/10.3390\/ijms17040578 (2016).","journal-title":"Int. J. Mol. Sci."},{"key":"53592_CR22","doi-asserted-by":"crossref","unstructured":"Van Klinken, B. J., Van der Wal, J. W., Einerhand, A. W., B\u00fcller, H. A. & Dekker, J. Sulphation and secretion of the predominant secretory human colonic mucin MUC2 in ulcerative colitis. Gut 44, 387\u2013393 (1999).","DOI":"10.1136\/gut.44.3.387"},{"key":"53592_CR23","doi-asserted-by":"publisher","unstructured":"Xu, P. et al. Intestinal sulfation is essential to protect against colitis and colonic carcinogenesis. Gastroenterology 161, 271\u2013286. https:\/\/doi.org\/10.1053\/j.gastro.2021.03.048 (2021).","DOI":"10.1053\/j.gastro.2021.03.048"},{"key":"53592_CR24","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1002\/ibd.21625","volume":"17","author":"JM Larsson","year":"2011","unstructured":"Larsson, J. M. et al. Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm. Bowel Dis. 17, 2299\u20132307. https:\/\/doi.org\/10.1002\/ibd.21625 (2011).","journal-title":"Inflamm. Bowel Dis."},{"key":"53592_CR25","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.diff.2008.09.008","volume":"77","author":"M Gersemann","year":"2009","unstructured":"Gersemann, M. et al. Differences in goblet cell differentiation between Crohn\u2019s disease and ulcerative colitis. Differentiation 77, 84\u201394. https:\/\/doi.org\/10.1016\/j.diff.2008.09.008 (2009).","journal-title":"Differentiation"},{"key":"53592_CR26","first-page":"252","volume":"56","author":"A Takeda","year":"2009","unstructured":"Takeda, A., Bari, S., Iseki, H., Otani, Y. & Koyama, I. Gastric differentiation markers expression is potentially useful for the detection of ulcerative colitis-associated dysplasias. Hepato Gastroenterol. 56, 252\u2013253 (2009).","journal-title":"Hepato-Gastroenterology"},{"key":"53592_CR27","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.humpath.2023.11.011","volume":"143","author":"E Musulen","year":"2024","unstructured":"Musulen, E. et al. Gastric metaplasia as a precursor of nonconventional dysplasia in inflammatory bowel disease. Hum. Pathol. 143, 50\u201361. https:\/\/doi.org\/10.1016\/j.humpath.2023.11.011 (2024).","journal-title":"Hum. Pathol."},{"key":"53592_CR28","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/s00795-020-00274-2","volume":"54","author":"SD Rico","year":"2021","unstructured":"Rico, S. D. et al. Elevated MUC5AC expression is associated with mismatch repair deficiency and proximal tumor location but not with cancer progression in colon cancer. Med. Mol. Morphol. 54, 156\u2013165. https:\/\/doi.org\/10.1007\/s00795-020-00274-2 (2021).","journal-title":"Med. Mol. Morphol."},{"key":"53592_CR29","doi-asserted-by":"publisher","unstructured":"Cantero-Recasens, G. et al. The ulcerative colitis-associated gene FUT8 regulates the quantity and quality of secreted mucins. Proc. Natl Acad. Sci. U. S. A. 119, e2205277119 (2022). https:\/\/doi.org\/10.1073\/pnas.2205277119","DOI":"10.1073\/pnas.2205277119"},{"key":"53592_CR30","doi-asserted-by":"publisher","first-page":"324","DOI":"10.3390\/ph16020324","volume":"16","author":"SJ Alarfaj","year":"2023","unstructured":"Alarfaj, S. J. et al. Mucosal genes expression in inflammatory bowel disease patients: New insights. Pharmaceuticals 16, 324. https:\/\/doi.org\/10.3390\/ph16020324 (2023).","journal-title":"Pharmaceuticals (Basel)"},{"key":"53592_CR31","doi-asserted-by":"publisher","unstructured":"Mizoshita, T. et al. Colon mucosa exhibits loss of ectopic MUC5AC expression in patients with ulcerative colitis treated with oral tacrolimus. ISRN Gastroenterol. 2013, 304894. https:\/\/doi.org\/10.1155\/2013\/304894 (2013).","DOI":"10.1155\/2013\/304894"},{"key":"53592_CR32","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1093\/ibd\/izaa064","volume":"26","author":"KE Olli","year":"2020","unstructured":"Olli, K. E. et al. Muc5ac expression protects the colonic barrier in experimental colitis. Inflamm. Bowel Dis. 26, 1353\u20131367. https:\/\/doi.org\/10.1093\/ibd\/izaa064 (2020).","journal-title":"Inflamm. Bowel Dis."},{"key":"53592_CR33","doi-asserted-by":"publisher","first-page":"108082","DOI":"10.4253\/wjge.v17.i7.108082","volume":"17","author":"T Chaemsupaphan","year":"2025","unstructured":"Chaemsupaphan, T. et al. Endocytoscopy in real-time assessment of histological and endoscopic activity in ulcerative colitis. World J. Gastrointest. Endosc. 17, 108082 (2025).","journal-title":"World J. Gastrointest. Endosc"},{"key":"53592_CR34","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.gie.2002.08.023","volume":"97","author":"F Vitali","year":"2023","unstructured":"Vitali, F. et al. Endocytoscopy for assessing histologic inflammation in ulcerative colitis: Development and prospective validation of the ELECT (ErLangen Endocytoscopy in ColiTis) score (with videos). Gastrointest. Endosc. 97, 100\u2013111. https:\/\/doi.org\/10.1016\/j.gie.2002.08.023 (2023).","journal-title":"Gastrointest. Endosc"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53592-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53592-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53592-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:03:12Z","timestamp":1787742192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-53592-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["53592"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-53592-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"assertion":[{"value":"19 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"26692"}}