Changing gastrointestinal transit time alters microbiome composition and bile acid metabolism: a cross‐over study in healthy volunteers
Author(s)
Type
Journal Article
Abstract
Background
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.
Methods
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.
Key Results
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.
Conclusion
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.
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.
Methods
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.
Key Results
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.
Conclusion
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.
Date Issued
2025-10-01
Date Acceptance
2025-04-30
Citation
Neurogastroenterology and Motility, 2025, 37 (10)
ISSN
1350-1925
Publisher
Wiley
Journal / Book Title
Neurogastroenterology and Motility
Volume
37
Issue
10
Copyright Statement
© 2025 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
10.1111/nmo.70075
Subjects
bile acids metabolism | gastrointestinal homeostasis | loperamide and senna treatment | microbiome | whole-gut transit-time (WGTT) BAD, bile acid diarrhea
BAI, bile acid-inducible
BL-L, baseline before loperamide
BL-S, baseline before Senna
BSH, bile salt hydrolase
C4, 7α-hydroxy-4-cholesten-3-one
CA, cholic acid
CDCA, chenodeoxycholic acid
CRC, colorectal cancer
DCA, deoxycholic acid
ELISA, enzyme-linked immunosorbent assay
FGF19, fibroblast growth factor 19
GCA, glycocholic acid
GCDA, glycochenodeoxycholic acid
GI, gastrointestinal
GUDCA, glycoursodeoxycholic acid
HCA, hyocholic acid
HDCA, hyodeoxycholic acid
HPLC-MS/MS, high-performance liquid chromatography coupled to tandem mass spectrometry
IBS, irritable bowel syndrome
IDI, inter-defecatory interval
LCA, lithocholic acid
LC-MS/MS, liquid chromatography-tandem mass spectrometry
MCA, muricholic acid
PCR, polymerase chain reaction
SCFAs, short-chain fatty acids
TCA, taurocholic acid
TCDCA, taurochenodeoxycholic acid
TUDCA, tauroursodeoxycholic acid
UDCA, ursodeoxycholic acid
WGTT, whole-gut transit time
Publication Status
Published
Article Number
e70075
Date Publish Online
2025-05-20