{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T19:44:58Z","timestamp":1784058298411,"version":"3.55.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012479","name":"General Research Fund of Shanghai Normal University","doi-asserted-by":"publisher","award":["12100323"],"award-info":[{"award-number":["12100323"]}],"id":[{"id":"10.13039\/501100012479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2414050003325"],"award-info":[{"award-number":["2414050003325"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["C2004-23Y"],"award-info":[{"award-number":["C2004-23Y"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.phrs.2025.107810","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T16:16:58Z","timestamp":1748621818000},"page":"107810","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Gut microbe-derived aromatic trace amines mediate individual variability in response to herbal medicine CDD-2101 for functional constipation"],"prefix":"10.1016","volume":"217","author":[{"given":"Shifa","family":"Ruan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwan","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanting","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hetong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing Lam Wendy","family":"To","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunsu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3907-5910","authenticated-orcid":false,"given":"Lixiang","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxiang","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9","key":"10.1016\/j.phrs.2025.107810_bib1","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/ajg.2011.164","article-title":"Prevalence of, and risk factors for, chronic idiopathic constipation in the community: systematic review and meta-analysis","volume":"106","author":"Suares","year":"2011","journal-title":"Off. J. Am. Coll. Gastroenterol. | ACG"},{"issue":"5","key":"10.1016\/j.phrs.2025.107810_bib2","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1053\/j.gastro.2012.08.002","article-title":"Burden of gastrointestinal disease in the United States: 2012 update","volume":"143","author":"Peery","year":"2012","journal-title":"Gastroenterology"},{"issue":"7","key":"10.1016\/j.phrs.2025.107810_bib3","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1053\/j.gastro.2015.08.045","article-title":"Burden of gastrointestinal, liver, and pancreatic diseases in the United States","volume":"149","author":"Peery","year":"2015","journal-title":"Gastroenterology"},{"issue":"9","key":"10.1016\/j.phrs.2025.107810_bib4","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1136\/gutjnl-2016-311835","article-title":"Comparison of efficacy of pharmacological treatments for chronic idiopathic constipation: a systematic review and network meta-analysis","volume":"66","author":"Nelson","year":"2017","journal-title":"Gut"},{"issue":"2","key":"10.1016\/j.phrs.2025.107810_bib5","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/apt.13662","article-title":"Systematic review with meta-analysis: effect of fibre supplementation on chronic idiopathic constipation in adults","volume":"44","author":"Christodoulides","year":"2016","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"12","key":"10.1016\/j.phrs.2025.107810_bib6","first-page":"660","article-title":"The effect of an anthraquinone laxative on colonic nerve tissue: a controlled trial in constipated women","volume":"28","author":"Riecken","year":"1990","journal-title":"Z. fur Gastroenterol."},{"issue":"9","key":"10.1016\/j.phrs.2025.107810_bib7","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1111\/j.1572-0241.2007.01365.x","article-title":"A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation","volume":"102","author":"Di Palma","year":"2007","journal-title":"Off. J. Am. Coll. Gastroenterol. | ACG"},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib8","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/ajg.2010.305","article-title":"Efficacy of a Chinese herbal proprietary medicine (Hemp Seed Pill) for functional constipation","volume":"106","author":"Cheng","year":"2011","journal-title":"Off. J. Am. Coll. Gastroenterol. | ACG"},{"key":"10.1016\/j.phrs.2025.107810_bib9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1745-6215-14-366","article-title":"Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial","volume":"14","author":"Zhong","year":"2013","journal-title":"Trials"},{"issue":"7","key":"10.1016\/j.phrs.2025.107810_bib10","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.cgh.2018.04.005","article-title":"Efficacy of MaZiRenWan, a Chinese herbal medicine, in patients with functional constipation in a randomized controlled trial","volume":"17","author":"Zhong","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"issue":"2","key":"10.1016\/j.phrs.2025.107810_bib11","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1053\/j.gastro.2015.12.023","article-title":"Constipation and the microbiome: lumen versus mucosa!","volume":"150","author":"Quigley","year":"2016","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1136\/gutjnl-2012-302167","article-title":"Intestinal microbiota in functional bowel disorders: a Rome foundation report","volume":"62","author":"Simr\u00e9n","year":"2013","journal-title":"Gut"},{"key":"10.1016\/j.phrs.2025.107810_bib13","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2019.00019","article-title":"Gut microbiota and chronic constipation: a review and update","volume":"6","author":"Ohkusa","year":"2019","journal-title":"Front. Med."},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib14","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1136\/gutjnl-2015-309618","article-title":"Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates","volume":"65","author":"Vandeputte","year":"2016","journal-title":"Gut"},{"key":"10.1016\/j.phrs.2025.107810_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2022.961703","article-title":"Role of gut microbiota-derived signals in the regulation of gastrointestinal motility","volume":"9","author":"Zheng","year":"2022","journal-title":"Front. Med."},{"issue":"7","key":"10.1016\/j.phrs.2025.107810_bib16","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2017.51","article-title":"Non-conventional features of peripheral serotonin signalling - the gut and beyond","volume":"14","author":"Spohn","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"9","key":"10.1016\/j.phrs.2025.107810_bib17","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1002\/jgh3.12528","article-title":"Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology","volume":"5","author":"Wei","year":"2021","journal-title":"JGH Open"},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib18","article-title":"Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine","volume":"7","author":"Cao","year":"2017","journal-title":"Sci. Rep."},{"issue":"19","key":"10.1016\/j.phrs.2025.107810_bib19","doi-asserted-by":"crossref","DOI":"10.3390\/ijms221910235","article-title":"Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome","volume":"22","author":"Mishima","year":"2021","journal-title":"Int J. Mol. Sci."},{"issue":"2","key":"10.1016\/j.phrs.2025.107810_bib20","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/fsn3.3826","article-title":"Exploring the serotonin-probiotics-gut health axis: A review of current evidence and potential mechanisms","volume":"12","author":"Akram","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"10.1016\/j.phrs.2025.107810_bib21","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ebiom.2017.09.020","article-title":"Microbiota-related changes in bile acid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism","volume":"24","author":"Golubeva","year":"2017","journal-title":"EBioMedicine"},{"key":"10.1016\/j.phrs.2025.107810_bib22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-016-1105-4","article-title":"Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility","volume":"15","author":"Ge","year":"2017","journal-title":"J. Transl. Med."},{"issue":"2","key":"10.1016\/j.phrs.2025.107810_bib23","doi-asserted-by":"crossref","first-page":"127","DOI":"10.5582\/bst.2024.01036","article-title":"Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora","volume":"18","author":"Wang","year":"2024","journal-title":"Biosci. Trends"},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.chom.2022.11.006","article-title":"Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis","volume":"31","author":"Zhai","year":"2023","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.phrs.2025.107810_bib25","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3389\/fphar.2018.00270","article-title":"Uncovering the Mechanisms of Chinese Herbal Medicine (MaZiRenWan) for Functional Constipation by Focused Network Pharmacology Approach","volume":"9","author":"Huang","year":"2018","journal-title":"Front Pharm."},{"key":"10.1016\/j.phrs.2025.107810_bib26","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3389\/fphys.2018.01534","article-title":"Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria","volume":"9","author":"Kennedy","year":"2018","journal-title":"Front Physiol."},{"issue":"12","key":"10.1016\/j.phrs.2025.107810_bib27","doi-asserted-by":"crossref","DOI":"10.1111\/nmo.13148","article-title":"Targeting fatty acid amide hydrolase and transient receptor potential vanilloid-1 simultaneously to modulate colonic motility and visceral sensation in the mouse: a pharmacological intervention with N-arachidonoyl-serotonin (AA-5-HT)","volume":"29","author":"Bashashati","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"issue":"6","key":"10.1016\/j.phrs.2025.107810_bib28","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3920\/BM2022.0052","article-title":"Ingestion of Lactobacillus helveticus WHH1889 improves depressive and anxiety symptoms induced by chronic unpredictable mild stress in mice","volume":"13","author":"Gao","year":"2022","journal-title":"Benef. Microbes"},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib29","article-title":"Spexin enhances bowel movement through activating L-type voltage-dependent calcium channel via galanin receptor 2 in mice","volume":"5","author":"Lin","year":"2015","journal-title":"Sci. Rep."},{"issue":"6","key":"10.1016\/j.phrs.2025.107810_bib30","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.tips.2018.03.004","article-title":"Peripheral serotonin synthesis as a new drug target","volume":"39","author":"Matthes","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"issue":"2","key":"10.1016\/j.phrs.2025.107810_bib31","doi-asserted-by":"crossref","first-page":"G260","DOI":"10.1152\/ajpgi.00056.2008","article-title":"Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants","volume":"295","author":"Kidd","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"issue":"3","key":"10.1016\/j.phrs.2025.107810_bib32","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1124\/pr.117.015305","article-title":"Trace Amines and Their Receptors","volume":"70","author":"Gainetdinov","year":"2018","journal-title":"Pharm. Rev."},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib33","doi-asserted-by":"crossref","first-page":"4986","DOI":"10.1038\/s41467-023-40552-y","article-title":"Gut microbiota-derived tryptamine and phenethylamine impair insulin sensitivity in metabolic syndrome and irritable bowel syndrome","volume":"14","author":"Zhai","year":"2023","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib34","doi-asserted-by":"crossref","first-page":"2128605","DOI":"10.1080\/19490976.2022.2128605","article-title":"Gut bacterial aromatic amine production: aromatic amino acid decarboxylase and its effects on peripheral serotonin production","volume":"14","author":"Sugiyama","year":"2022","journal-title":"Gut Microbes"},{"issue":"6","key":"10.1016\/j.phrs.2025.107810_bib35","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.chom.2018.05.004","article-title":"Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion","volume":"23","author":"Bhattarai","year":"2018","journal-title":"Cell Host Microbe"},{"issue":"11","key":"10.1016\/j.phrs.2025.107810_bib36","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1017\/S0007114508123431","article-title":"Effects of dietary amines on the gut and its vasculature","volume":"101","author":"Broadley","year":"2009","journal-title":"Br. J. Nutr."},{"issue":"10","key":"10.1016\/j.phrs.2025.107810_bib37","doi-asserted-by":"crossref","DOI":"10.3390\/nu13103445","article-title":"Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility","volume":"13","author":"Amato","year":"2021","journal-title":"Nutrients"},{"issue":"23","key":"10.1016\/j.phrs.2025.107810_bib38","doi-asserted-by":"crossref","DOI":"10.3390\/ijms252313216","article-title":"Functional Analysis of TAAR1 Expression in the Intestine Wall and the Effect of Its Gene Knockout on the Gut Microbiota in Mice","volume":"25","author":"Vaganova","year":"2024","journal-title":"Int J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12929-020-00688-1","article-title":"The trace aminergic system: a gender-sensitive therapeutic target for IBS?","volume":"27","author":"Pretorius","year":"2020","journal-title":"J. Biomed. Sci."},{"issue":"1","key":"10.1016\/j.phrs.2025.107810_bib40","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1177\/2050640614558476","article-title":"Chronic constipation and co-morbidities: A prospective population-based nested case-control study","volume":"4","author":"Choung","year":"2016","journal-title":"U. Eur. Gastroenterol. J."},{"key":"10.1016\/j.phrs.2025.107810_bib41","doi-asserted-by":"crossref","first-page":"1105272","DOI":"10.3389\/fcimb.2023.1105272","article-title":"Improvement of loperamide-hydrochloride-induced intestinal motility disturbance by Platycodon grandiflorum polysaccharides through effects on gut microbes and colonic serotonin","volume":"13","author":"Hao","year":"2023","journal-title":"Front Cell Infect. Microbiol"},{"key":"10.1016\/j.phrs.2025.107810_bib42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.coph.2018.08.008","article-title":"Opioid receptors in the GI tract: targets for treatment of both diarrhea and constipation in functional bowel disorders?","volume":"43","author":"Pannemans","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"issue":"9","key":"10.1016\/j.phrs.2025.107810_bib43","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1177\/0271678X20943823","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"40","author":"Percie du Sert","year":"2020","journal-title":"J. Cereb. Blood Flow. Metab."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104366182500235X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S104366182500235X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:37:48Z","timestamp":1778582268000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S104366182500235X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":43,"alternative-id":["S104366182500235X"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107810","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Gut microbe-derived aromatic trace amines mediate individual variability in response to herbal medicine CDD-2101 for functional constipation","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2025.107810","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"107810"}}