{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:36:50Z","timestamp":1788831410880,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Radiation therapy\u2010induced gastrointestinal distress is partly associated with the elimination of gut microbiota. The effectiveness of 5\u2010HT receptor antagonists to treat radiation therapy\u2010induced emesis implies a pathophysiological role of 5\u2010HT. Peripheral 5\u2010HT is derived from intestinal epithelium. We have investigated the role of gut microbiota in regulating intestinal 5\u2010HT availability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A radiation therapy murine model accompanied by faecal microbiota transplantation from donors fed different diets was investigated, and mouse ileal organoids were used for mechanistic studies. The clinical relevance was validated by a small\u2010scale human study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Short\u2010term high\u2010fat diet (HFD) induced gut bacteria to produce butyrate. Irradiated mice receiving HFD\u2010induced microbiome had the lowest ileal levels of 5\u2010HT, compared with other recipients. Treatment with butyrate increased 5\u2010HT uptake in mouse ileal organoids, assayed by the real\u2010time tracking of a fluorescent substrate for monoamine transporters. Silencing the 5\u2010HT transporter (SERT) in the organoids abolished butyrate\u2010stimulated 5\u2010HT uptake. The competitive tests using different types of selective 5\u2010HT reuptake inhibitors suggested that butyrate acted as a positive allosteric modulator of SERT. In human gut microbiota, butyrate production was associated with the interconversion between acetate and butyrate. Faecal contents of both acetate and butyrate were negatively associated with serum 5\u2010HT, but only butyrate was positively correlated with body mass index in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Short\u2010term HFD may be beneficial for alleviating gastrointestinal reactions by increasing butyrate to suppress local 5\u2010HT levels and providing energy to cancer patients given radiation therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16305","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T05:10:08Z","timestamp":1703221808000},"page":"1654-1670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Butyrate acts as a positive allosteric modulator of the 5\u2010HT transporter to decrease availability of 5\u2010HT in the ileum"],"prefix":"10.1111","volume":"181","author":[{"given":"Jieling","family":"Cai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Cheung","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"},{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine The University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samson W. 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