{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:28:33Z","timestamp":1785112113430,"version":"3.55.0"},"reference-count":56,"publisher":"Wiley","issue":"4","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\/"}],"funder":[{"DOI":"10.13039\/501100000837","name":"University of Nottingham","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti\u2010diarrheal actions of ondansetron.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A double\u2010blind, randomized, placebo\u2010controlled crossover study of the effect of ondansetron 8\u2009mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6\u2009h after a meal. Participants then received lactulose 13.6\u2009g twice daily and study drug for a further 36\u2009h. On Day 3, they had further serial MRI scans for 4\u2009h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Lactulose increased area under the curve (AUC) of SBWC from 0 to 240\u2009min, mean difference 14.2\u2009L\u2009\u00b7\u2009min (95% CI 4.1, 24.3), <jats:italic>p<\/jats:italic>\u2009=\u20090.009, and substantially increased small bowel motility after 4\u2009h (mean (95% CI) 523 (457\u2013646) a.u. to 852 (771\u20131178) a.u., <jats:italic>p<\/jats:italic>\u2009=\u20090.007). There were no changes in T1AC after 36\u2009h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion &amp; Inferences<\/jats:title><jats:p>Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti\u2010diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.14754","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T07:49:40Z","timestamp":1707292180000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanisms underlying the laxative effect of lactulose: A randomized placebo\u2010controlled trial showing increased small bowel water and motility unaltered by the <scp>5\u2010HT<sub>3<\/sub><\/scp> receptor antagonist, ondansetron"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1436-7754","authenticated-orcid":false,"given":"D.","family":"Gunn","sequence":"first","affiliation":[{"name":"NIHR Nottingham Biomedical Research Centre  Nottingham UK"},{"name":"Nottingham Digestive Diseases Centre 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