{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:44:12Z","timestamp":1791909852328,"version":"4.3.4"},"reference-count":37,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Aims. Melatonin is a ubiquitous hormone produced not only by the pineal gland but also by other organs and tissues. It is involved in the regulation of several gastrointestinal functions. The main cells responsible for the production and release of extrapineal melatonin are the enterochromaffin (EC) cells that produce serotonin. They are involved in the pathogenesis of neuromotor disorders that characterize functional gastrointestinal disorders and in the pathophysiology of inflammatory intestinal diseases. Our aim was the immunohistochemical highlighting on biopsy samples of normal gastrointestinal mucosa and in ulcerative colitis (UC) of immunoreactive cells for melatonin and serotonin in order to identify any differences in their distribution. Materials and Methods. Our prospective case-control study involves the highlighting on human mucosal biopsies of immunoreactive cells for melatonin and serotonin. All patients undergoing colonoscopy + ileoscopy were considered eligible for the study, divided into two groups: 1. patients with active ulcerative colitis (UC); 2. control group consisting of patients undergoing endoscopic examination for colorectal cancer screening. Results. Twenty-one patients were enrolled. The controls had a higher concentration of EC cells containing 5HT particularly in the rectum (p value \u2264 0.05). In patients with active colitis the expression of 5-HT-iR was greater in all tracts of the colon. The correlation analysis in UC patients shows that a higher expression of 5-HT-iR+ cells corresponds to a lower extension of the disease and a greater severity of the same. Conclusions. 5HT+ cells decreased in the case of UC compared to healthy controls. In the severe disease, there was an increase in the expression of melatonin-secreting cells, probably as a compensatory response to the inflammation and oxidative stress. This increase is negatively correlated with the extent of the disease and positively with the severity of the same.<\/jats:p>","DOI":"10.3390\/diagnostics13020204","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:11:51Z","timestamp":1672899111000},"page":"204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Serotonin and Melatonin in Human Lower Gastrointestinal Tract"],"prefix":"10.3390","volume":"13","author":[{"given":"Rosa","family":"Vaccaro","sequence":"first","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Casini","sequence":"additional","affiliation":[{"name":"Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9249-1318","authenticated-orcid":false,"given":"Carola","family":"Severi","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Lamazza","sequence":"additional","affiliation":[{"name":"Department of General, Plastic and Urologic Surgery, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-8902","authenticated-orcid":false,"given":"Annamaria","family":"Pronio","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialties, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-552X","authenticated-orcid":false,"given":"Rossella","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Surgical Specialties, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"ref_1","first-page":"381","article-title":"Localization and biological activities of melatonin in intact and diseased gastrointestinal tract","volume":"58","author":"Konturek","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e14241","DOI":"10.1097\/MD.0000000000014241","article-title":"Melatonin for the treatment of gastroesophageal reflux disease; protocol for a systematic review and meta-analysis","volume":"98","author":"Bang","year":"2019","journal-title":"Medicine"},{"key":"ref_3","first-page":"97","article-title":"Melatonin and serotonin effects on gastrointestinal motility","volume":"58","author":"Thor","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.lfs.2016.11.031","article-title":"Melatonin\u2019s role as a co-adjuvant treatment in colonic diseases: A review","volume":"170","author":"Tan","year":"2017","journal-title":"Life Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cca.2011.06.036","article-title":"Detection of melatonin and homocysteine simutaneously in ulcerative colitis","volume":"413","author":"Chen","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_6","first-page":"67","article-title":"Is melatonin involved in the irritable bowel syndrome?","volume":"60","author":"Radwan","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.regpep.2013.03.016","article-title":"Evaluation of melatonin and prostaglandin E1 combination on necrotizing enterocolitis model in neonatal rats","volume":"184","author":"Tayman","year":"2013","journal-title":"Regul. Pept."},{"key":"ref_8","unstructured":"Vaccaro, R., Severi, C., Casini, A., Pronio, A., Zaccari, P., Anastasi, E., and Onori, P. (2019). Serotonin and melatonin immunoreactivity in human gastrointestinal tract. Ital. J. Anat. Embryol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1159\/000046903","article-title":"Localization, biological significance and possible clinical implication of gastrointestinal melatonin","volume":"10","author":"Bubenik","year":"2001","journal-title":"Biol. Signals Recept."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S184","DOI":"10.1097\/01.mcg.0000156403.37240.30","article-title":"Nerves, reflexes and enteric nervous system pathogenesis of the irritable bowel syndrome","volume":"39","author":"Gershon","year":"2005","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5151","DOI":"10.3748\/wjg.v18.i37.5151","article-title":"Irritable bowel syndrome: Diagnosis and pathogenesis","volume":"18","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1038\/ajg.2011.58","article-title":"An Evidence-Based Systematic Review on Medical Therapies for Inflammatory Bowel Disease","volume":"106","author":"Talley","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_13","first-page":"247","article-title":"Inflammatory bowel disease Part 1: Ulcerative colitis--pathophysiology and conventional and alternative treatment options","volume":"8","author":"Head","year":"2003","journal-title":"Altern. Med. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/path.1409","article-title":"Intestinal oxidative damage in inflammatory bowel disease: Semiquantification, localization, and association with mucosal antioxidants","volume":"201","author":"Kruidenier","year":"2003","journal-title":"J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1053\/j.gastro.2011.02.016","article-title":"Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases","volume":"140","author":"Strober","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cei.12474","article-title":"Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota","volume":"179","author":"Peterson","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_17","first-page":"CD001176","article-title":"Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis","volume":"6","author":"Holubar","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1136\/gut.2004.052316","article-title":"Retarded release phosphatidylcholine benefits patients with chronic active ulcerative colitis","volume":"54","author":"Stremmel","year":"2005","journal-title":"Gut"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory bowel disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Chojnacki, C., B\u0142asiak, J., Fichna, J., Chojnacki, J., and Pop\u0142awski, T. (2018). Evaluation of Melatonin Secretion and Metabolism Exponents in Patients with Ulcerative and Lymphocytic Colitis. Molecules, 23.","DOI":"10.3390\/molecules23020272"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1053\/j.gastro.2020.01.006","article-title":"AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis","volume":"158","author":"Feuerstein","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_22","unstructured":"Vashist, N.M., Samaan, M., Mosli, M.H., Parker, C.E., MacDonald, J.K., Nelson, S.A., Zou, G.Y., Feagan, B.G., Khanna, R., and Jairath, V. (2018). Endoscopic scoring indices for evaluation of disease activity in ulcerative colitis (Review). Cochrane Database Syst. Rev., CD011450."},{"key":"ref_23","first-page":"423","article-title":"The modulatory role of melatonin on immune responsiveness","volume":"7","author":"Reiter","year":"2006","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_24","first-page":"882","article-title":"Melatonin reduces colon immunological injury in rats by regulating activity of macrophages","volume":"23","author":"Mei","year":"2002","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ejphar.2007.11.031","article-title":"Melatonin inhibits prostaglandin E2- and sodium nitroprusside-induced ion secretion in rat distal colon","volume":"581","author":"Mrnka","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3646","DOI":"10.2174\/138161210794079254","article-title":"Implications of melatonin therapy in irritable bowel syndrome: A systematic review","volume":"16","author":"Mozaffari","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1034\/j.1600-079X.2000.290303.x","article-title":"Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical","volume":"29","author":"Bandyopadhyay","year":"2000","journal-title":"J. Pineal Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/MCG.0b013e318031457a","article-title":"Therapeutic Effect of Melatonin in Patients With Functional Dyspepsia","volume":"41","author":"Poplawski","year":"2007","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1600-079X.2005.00264.x","article-title":"Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress-induced damage","volume":"39","author":"Brzozowski","year":"2005","journal-title":"J. Pineal Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11742","DOI":"10.3390\/ijms140611742","article-title":"Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases","volume":"14","author":"Lin","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e12394","DOI":"10.1111\/jpi.12394","article-title":"Melatonin signaling in T cells: Functions and applications","volume":"62","author":"Ren","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_32","first-page":"20","article-title":"Distribution of 5-OH tryptamine (serotonin) in ulcerative colitis","volume":"63","author":"Capurso","year":"1970","journal-title":"Proc. R. Soc. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1023\/A:1013256629600","article-title":"Impaired Synthesis or Cellular Storage of Norepinephrine, Dopamine, and 5-Hydroxytryptamine in Human Inflammatory Bowel Disease","volume":"47","author":"Magro","year":"2002","journal-title":"Dig. Dis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s004180050445","article-title":"Changes in number of serotonin-containing cells and serotonin levels in the intestinal mucosa of rats with colitis induced by dextran sodium sulfate","volume":"112","author":"Oshima","year":"1999","journal-title":"Histochem. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"G207","DOI":"10.1152\/ajpgi.00488.2002","article-title":"Serotonin availability is increased in mucosa of guinea pigs with TNBS-induced colitis","volume":"285","author":"Linden","year":"2003","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"G998","DOI":"10.1152\/ajpgi.00090.2004","article-title":"Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis","volume":"287","author":"Ho","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3602","DOI":"10.3748\/wjg.v19.i23.3602","article-title":"Evaluation of enterochromaffin cells and melatonin secretion exponents in ulcerative colitis","volume":"19","author":"Chojnacki","year":"2013","journal-title":"World J. Gastroenterol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/2\/204\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:00:05Z","timestamp":1760119205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/2\/204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["diagnostics13020204"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13020204","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]}}}