{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:07:13Z","timestamp":1785247633909,"version":"3.55.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Gastroenterol"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1007\/s00535-021-01838-4","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T07:03:25Z","timestamp":1638428605000},"page":"62-69","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Microinflammation in the intestinal mucosa and symptoms of irritable bowel syndrome"],"prefix":"10.1007","volume":"57","author":[{"given":"Takanori","family":"Yoshimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-932X","authenticated-orcid":false,"given":"Tadayuki","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Tomita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Miwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"1838_CR1","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1053\/j.gastro.2016.03.035","volume":"150","author":"DA Drossman","year":"2016","unstructured":"Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology. 2016;150:1257\u201361.","journal-title":"Gastroenterology"},{"key":"1838_CR2","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.cgh.2012.02.029","volume":"10","author":"RM Lovell","year":"2012","unstructured":"Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:712-21 e4.","journal-title":"Clin Gastroenterol Hepatol"},{"key":"1838_CR3","doi-asserted-by":"publisher","first-page":"320","DOI":"10.5056\/jnm14165","volume":"21","author":"T Oshima","year":"2015","unstructured":"Oshima T, Miwa H. Epidemiology of functional gastrointestinal disorders in Japan and in the world. J Neurogastroenterol Motil. 2015;21:320\u20139.","journal-title":"J Neurogastroenterol Motil"},{"key":"1838_CR4","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s00535-020-01746-z","volume":"56","author":"S Fukudo","year":"2021","unstructured":"Fukudo S, Okumura T, Inamori M, et al. Evidence-based clinical practice guidelines for irritable bowel syndrome 2020. J Gastroenterol. 2021;56:193\u2013217.","journal-title":"J Gastroenterol"},{"key":"1838_CR5","first-page":"578","volume":"368","author":"M Camilleri","year":"2013","unstructured":"Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2013;368:578\u20139.","journal-title":"N Engl J Med"},{"key":"1838_CR6","doi-asserted-by":"publisher","first-page":"467","DOI":"10.4103\/0976-3147.168422","volume":"6","author":"T Oshima","year":"2015","unstructured":"Oshima T, Miwa H. Irritable bowel syndrome: what physicians should know? J Neurosci Rural Pract. 2015;6:467\u20138.","journal-title":"J Neurosci Rural Pract"},{"key":"1838_CR7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/s41395-018-0377-0","volume":"114","author":"G Burns","year":"2019","unstructured":"Burns G, Carroll G, Mathe A, et al. Evidence for local and systemic immune activation in functional dyspepsia and the irritable bowel syndrome: a systematic review. Am J Gastroenterol. 2019;114:429\u201336.","journal-title":"Am J Gastroenterol"},{"key":"1838_CR8","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1053\/gast.2002.33579","volume":"122","author":"VS Chadwick","year":"2002","unstructured":"Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122:1778\u201383.","journal-title":"Gastroenterology"},{"key":"1838_CR9","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1111\/1751-2980.12379","volume":"17","author":"JJ Martin-Vinas","year":"2016","unstructured":"Martin-Vinas JJ, Quigley EM. Immune response in irritable bowel syndrome: a systematic review of systemic and mucosal inflammatory mediators. J Dig Dis. 2016;17:572\u201381.","journal-title":"J Dig Dis"},{"key":"1838_CR10","doi-asserted-by":"publisher","first-page":"628","DOI":"10.5056\/jnm18130","volume":"24","author":"R Shukla","year":"2018","unstructured":"Shukla R, Ghoshal U, Ranjan P, et al. Expression of toll-like receptors, pro-, and anti-inflammatory cytokines in relation to gut microbiota in irritable bowel syndrome: the evidence for its micro-organic basis. J Neurogastroenterol Motil. 2018;24:628\u201342.","journal-title":"J Neurogastroenterol Motil"},{"key":"1838_CR11","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1111\/nmo.12315","volume":"26","author":"T Piche","year":"2014","unstructured":"Piche T. Tight junctions and IBS\u2013the link between epithelial permeability, low-grade inflammation, and symptom generation? Neurogastroenterol Motil. 2014;26:296\u2013302.","journal-title":"Neurogastroenterol Motil"},{"key":"1838_CR12","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3164\/jcbn.16-92","volume":"60","author":"H Ishimoto","year":"2017","unstructured":"Ishimoto H, Oshima T, Sei H, et al. Claudin-2 expression is upregulated in the ileum of diarrhea predominant irritable bowel syndrome patients. J Clin Biochem Nutr. 2017;60:146\u201350.","journal-title":"J Clin Biochem Nutr"},{"key":"1838_CR13","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1159\/000502953","volume":"102","author":"M Li","year":"2021","unstructured":"Li M, Oshima T, Ito C, et al. Glutamine blocks interleukin-13-induced intestinal epithelial barrier dysfunction. Digestion. 2021;102:170\u2013179. https:\/\/doi.org\/10.1159\/000502953.","journal-title":"Digestion."},{"key":"1838_CR14","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1111\/jgh.15225","volume":"36","author":"K Miura","year":"2021","unstructured":"Miura K, Oshima T, Ito C, et al. Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2021;36:951\u20138.","journal-title":"J Gastroenterol Hepatol"},{"key":"1838_CR15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1136\/gut.2006.100594","volume":"56","author":"M Guilarte","year":"2007","unstructured":"Guilarte M, Santos J, de Torres I, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56:203\u20139.","journal-title":"Gut"},{"key":"1838_CR16","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1007\/BF01303164","volume":"38","author":"AP Weston","year":"1993","unstructured":"Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993;38:1590\u20135.","journal-title":"Dig Dis Sci"},{"key":"1838_CR17","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1046\/j.1365-2982.2000.00221.x","volume":"12","author":"M O'Sullivan","year":"2000","unstructured":"O\u2019Sullivan M, Clayton N, Breslin NP, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000;12:449\u201357.","journal-title":"Neurogastroenterol Motil"},{"key":"1838_CR18","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1111\/j.1365-2036.2009.03937.x","volume":"29","author":"MM Walker","year":"2009","unstructured":"Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765\u201373.","journal-title":"Aliment Pharmacol Ther"},{"key":"1838_CR19","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1053\/j.gastro.2011.01.052","volume":"140","author":"S Foley","year":"2011","unstructured":"Foley S, Garsed K, Singh G, et al. Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation. Gastroenterology. 2011;140:1434-43 e1.","journal-title":"Gastroenterology"},{"key":"1838_CR20","doi-asserted-by":"publisher","first-page":"e00296","DOI":"10.14309\/ctg.0000000000000296","volume":"12","author":"NJ Talley","year":"2020","unstructured":"Talley NJ, Alexander JL, Walker MM, et al. Ileocolonic histopathological and microbial alterations in the irritable bowel syndrome: a nested community case-control study. Clin Transl Gastroenterol. 2020;12:e00296.","journal-title":"Clin Transl Gastroenterol"},{"key":"1838_CR21","first-page":"171","volume":"31","author":"N Lazaridis","year":"2018","unstructured":"Lazaridis N, Germanidis G. Current insights into the innate immune system dysfunction in irritable bowel syndrome. Ann Gastroenterol. 2018;31:171\u201387.","journal-title":"Ann Gastroenterol"},{"key":"1838_CR22","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1053\/j.gastro.2003.09.028","volume":"125","author":"SP Dunlop","year":"2003","unstructured":"Dunlop SP, Jenkins D, Neal KR, et al. Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology. 2003;125:1651\u20139.","journal-title":"Gastroenterology"},{"key":"1838_CR23","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/ajg.2012.54","volume":"107","author":"B Braak","year":"2012","unstructured":"Braak B, Klooker TK, Wouters MM, et al. Mucosal immune cell numbers and visceral sensitivity in patients with irritable bowel syndrome: is there any relationship? Am J Gastroenterol. 2012;107:715\u201326.","journal-title":"Am J Gastroenterol"},{"key":"1838_CR24","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1136\/gutjnl-2013-306236","volume":"64","author":"M Vicario","year":"2015","unstructured":"Vicario M, Gonzalez-Castro AM, Martinez C, et al. Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations. Gut. 2015;64:1379\u201388.","journal-title":"Gut"},{"key":"1838_CR25","doi-asserted-by":"publisher","first-page":"537","DOI":"10.5056\/jnm15016","volume":"21","author":"M Kanazawa","year":"2015","unstructured":"Kanazawa M, Nakajima S, Oshima T, et al. Validity and Reliability of the Japanese Version of the Rome III diagnostic questionnaire for irritable bowel syndrome and functional dyspepsia. J Neurogastroenterol Motil. 2015;21:537\u201344.","journal-title":"J Neurogastroenterol Motil"},{"key":"1838_CR26","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1038\/s41395-018-0264-8","volume":"113","author":"T Oshima","year":"2018","unstructured":"Oshima T, Miwa H. Functional dyspepsia\u2014a revolution in management. Am J Gastroenterol. 2018;113:1420\u20132.","journal-title":"Am J Gastroenterol"},{"key":"1838_CR27","doi-asserted-by":"publisher","first-page":"463","DOI":"10.15403\/jgld-229","volume":"28","author":"L Krammer","year":"2019","unstructured":"Krammer L, Sowa AS, Lorentz A. Mast cells in irritable bowel syndrome: a systematic review. J Gastrointestin Liver Dis. 2019;28:463\u201372.","journal-title":"J Gastrointestin Liver Dis"},{"key":"1838_CR28","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3109\/00365521.2012.666672","volume":"47","author":"AP De Silva","year":"2012","unstructured":"De Silva AP, Nandasiri SD, Hewavisenthi J, et al. Subclinical mucosal inflammation in diarrhea-predominant irritable bowel syndrome (IBS) in a tropical setting. Scand J Gastroenterol. 2012;47:619\u201324.","journal-title":"Scand J Gastroenterol"},{"key":"1838_CR29","doi-asserted-by":"publisher","first-page":"e13701","DOI":"10.1111\/nmo.13701","volume":"31","author":"J Sundin","year":"2019","unstructured":"Sundin J, Nordlander S, Eutamene H, et al. Colonic mast cell numbers, symptom profile, and mucosal expression of elements of the epithelial barrier in irritable bowel syndrome. Neurogastroenterol Motil. 2019;31:e13701.","journal-title":"Neurogastroenterol Motil"},{"key":"1838_CR30","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nri1333","volume":"4","author":"H Cheroutre","year":"2004","unstructured":"Cheroutre H, Madakamutil L. Acquired and natural memory T cells join forces at the mucosal front line. Nat Rev Immunol. 2004;4:290\u2013300.","journal-title":"Nat Rev Immunol"},{"key":"1838_CR31","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/ni1101-997","volume":"2","author":"A Hayday","year":"2001","unstructured":"Hayday A, Theodoridis E, Ramsburg E, et al. Intraepithelial lymphocytes: exploring the Third Way in immunology. Nat Immunol. 2001;2:997\u20131003.","journal-title":"Nat Immunol"},{"key":"1838_CR32","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1007\/s10620-013-2930-4","volume":"59","author":"JY Ahn","year":"2014","unstructured":"Ahn JY, Lee KH, Choi CH, et al. Colonic mucosal immune activity in irritable bowel syndrome: comparison with healthy controls and patients with ulcerative colitis. Dig Dis Sci. 2014;59:1001\u201311.","journal-title":"Dig Dis Sci"},{"key":"1838_CR33","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1053\/j.gastro.2014.07.046","volume":"147","author":"A Fritscher-Ravens","year":"2014","unstructured":"Fritscher-Ravens A, Schuppan D, Ellrichmann M, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014;147:1012-20 e4.","journal-title":"Gastroenterology"},{"key":"1838_CR34","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1053\/j.gastro.2003.11.055","volume":"126","author":"G Barbara","year":"2004","unstructured":"Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693\u2013702.","journal-title":"Gastroenterology"},{"key":"1838_CR35","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1136\/gut.2007.127068","volume":"57","author":"T Piche","year":"2008","unstructured":"Piche T, Saint-Paul MC, Dainese R, et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 2008;57:468\u201373.","journal-title":"Gut"},{"key":"1838_CR36","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/ajg.2008.94","volume":"104","author":"C Cremon","year":"2009","unstructured":"Cremon C, Gargano L, Morselli-Labate AM, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104:392\u2013400.","journal-title":"Am J Gastroenterol"},{"key":"1838_CR37","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1136\/gutjnl-2012-302093","volume":"62","author":"C Martinez","year":"2013","unstructured":"Martinez C, Lobo B, Pigrau M, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut. 2013;62:1160\u20138.","journal-title":"Gut"},{"key":"1838_CR38","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/j.1365-2249.2011.04382.x","volume":"164","author":"Z Liu","year":"2011","unstructured":"Liu Z, Chen X, Wang X, et al. Chemokine CXCL11 links microbial stimuli to intestinal inflammation. Clin Exp Immunol. 2011;164:396\u2013406.","journal-title":"Clin Exp Immunol"},{"key":"1838_CR39","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1172\/JCI13543","volume":"108","author":"CH Kim","year":"2001","unstructured":"Kim CH, Rott L, Kunkel EJ, et al. Rules of chemokine receptor association with T cell polarization in vivo. J Clin Invest. 2001;108:1331\u20139.","journal-title":"J Clin Invest"}],"container-title":["Journal of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-021-01838-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00535-021-01838-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00535-021-01838-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T11:05:41Z","timestamp":1644491141000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00535-021-01838-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,2]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["1838"],"URL":"https:\/\/doi.org\/10.1007\/s00535-021-01838-4","relation":{},"ISSN":["0944-1174","1435-5922"],"issn-type":[{"value":"0944-1174","type":"print"},{"value":"1435-5922","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,2]]},"assertion":[{"value":"9 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no conflict of interest regarding this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}