biostudies-literatureUnknown37(10)Hillman EBMDepartment of Health and Social Care (DHSC) Policy Research Programme (NIBSC Regulatory Science Research Unit)<h4>Background</h4>The specific influence of whole gut transit time (WGTT) on microbiome dynamics and bile acid metabolism remains unclear, despite links between changes in WGTT and certain gastrointestinal disorders. Our investigation aimed to determine the impact of WGTT changes on the composition of the fecal microbiome and bile acid profile.<h4>Methods</h4>Healthy volunteers (n = 18) received loperamide, to decrease bowel movement frequency, and senna, a laxative, each over a 6-day period, in a randomized sequence, with a minimum 16-day interval between each treatment. Stool samples were analyzed for microbiome by shotgun sequencing and bile acid composition determined with high-performance liquid chromatography coupled to tandem mass spectrometry. Sera were examined for markers of bile acid synthesis.<h4>Key results</h4>Senna or loperamide decreased or increased WGTT, respectively. Treatment altered stool characteristics, bowel movement frequency, and stool weight. The senna-treated group had increased primary and secondary fecal bile acids; serum levels of fibroblast growth factor 19 were significantly reduced. Increasing WGTT with loperamide led to an increase in bile salt hydrolase genes, along with elevated bacterial species richness (p = 0.04). Thirty-six species exhibiting significant differences were identified, several of which have notable implications for gut health. WGTT displayed negative correlations with total primary (particularly chenodeoxycholic acid) and secondary bile acids (ursodeoxycholic acid and glycochenodeoxycholic acid). Treatment-induced changes in microbiome composition and bile acid metabolism reverted back to baseline within 16 days.<h4>Conclusion</h4>Whole gut transit time changes significantly affect fecal microbiome composition and function, as well as bile acid composition and synthesis in healthy subjects. This consideration is likely to have long-term implications.Neurogastroenterology and motilitye70075https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435802biostudies-literatureChanging Gastrointestinal Transit Time Alters Microbiome Composition and Bile Acid Metabolism: A Cross-Over Study in Healthy Volunteers.PMC12435802Hillman EBMArasaradnam RAmos GCALewis SJBaumgartner MWalters JRFWellington EMHRijpkema SKhan HACarson DWazir IKhan MAfalseChanging Gastrointestinal Transit Time Alters Microbiome Composition and Bile Acid Metabolism: A Cross-Over Study in Healthy Volunteers.<h4>Background</h4>The specific influence of whole gut transit time (WGTT) on microbiome dynamics and bile acid metabolism remains unclear, despite links between changes in WGTT and certain gastrointestinal disorders. Our investigation aimed to determine the impact of WGTT changes on the composition of the fecal microbiome and bile acid profile.<h4>Methods</h4>Healthy volunteers (n = 18) received loperamide, to decrease bowel movement frequency, and senna, a laxative, each over a 6-day period, in a randomized sequence, with a minimum 16-day interval between each treatment. Stool samples were analyzed for microbiome by shotgun sequencing and bile acid composition determined with high-performance liquid chromatography coupled to tandem mass spectrometry. Sera were examined for markers of bile acid synthesis.<h4>Key results</h4>Senna or loperamide decreased or increased WGTT, respectively. Treatment altered stool characteristics, bowel movement frequency, and stool weight. The senna-treated group had increased primary and secondary fecal bile acids; serum levels of fibroblast growth factor 19 were significantly reduced. Increasing WGTT with loperamide led to an increase in bile salt hydrolase genes, along with elevated bacterial species richness (p = 0.04). Thirty-six species exhibiting significant differences were identified, several of which have notable implications for gut health. WGTT displayed negative correlations with total primary (particularly chenodeoxycholic acid) and secondary bile acids (ursodeoxycholic acid and glycochenodeoxycholic acid). Treatment-induced changes in microbiome composition and bile acid metabolism reverted back to baseline within 16 days.<h4>Conclusion</h4>Whole gut transit time changes significantly affect fecal microbiome composition and function, as well as bile acid composition and synthesis in healthy subjects. This consideration is likely to have long-term implications.2025-01-01T00:00:00Z2025 Oct2026-06-01T15:45:58.743Z2026-04-08T13:48:06.182ZS-EPMC124358024039497210.1111/nmo.70075