Quantifying Forms and Functions of Enterohepatic Bile Acid Pools in Mice.
Cell Mol Gastroenterol Hepatol
; 18(6): 101392, 2024 Aug 22.
Article
in En
| MEDLINE
| ID: mdl-39179177
ABSTRACT
BACKGROUNDS & AIMS:
Bile acids (BAs) are core gastrointestinal metabolites with dual functions in lipid absorption and cell signaling. BAs circulate between the liver and distal small intestine (i.e., ileum), yet the dynamics through which complex BA pools are absorbed in the ileum and interact with host intestinal cells in vivo remain poorly understood. Because ileal absorption is rate-limiting in determining which BAs in the intestinal lumen gain access to host intestinal cells and receptors, and at what concentrations, we hypothesized that defining the rates and routes of ileal BA absorption in vivo would yield novel insights into the physiological forms and functions of mouse enterohepatic BA pools.METHODS:
Using ex vivo mass spectrometry, we quantified 88 BA species and metabolites in the intestinal lumen and superior mesenteric vein of individual wild-type mice, and cage-mates lacking the ileal BA transporter, Asbt/Slc10a2.RESULTS:
Using these data, we calculated that the pool of BAs circulating through ileal tissue (i.e., the ileal BA pool) in fasting C57BL/6J female mice is â¼0.3 µmol/g. Asbt-mediated transport accounted for â¼80% of this pool and amplified size. Passive permeability explained the remaining â¼20% and generated diversity. Compared with wild-type mice, the ileal BA pool in Asbt-deficient mice was â¼5-fold smaller, enriched in secondary BA species and metabolites normally found in the colon, and elicited unique transcriptional responses on addition to exvivo-cultured ileal explants.CONCLUSIONS:
This study defines quantitative traits of the mouse enterohepatic BA pool and reveals how aberrant BA metabolism can impinge directly on host intestinal physiology.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Cell Mol Gastroenterol Hepatol
/
Cell Mol. Gastroenterol. Hepatol
/
Cellular and molecular gastroenterology and hepatology
Year:
2024
Document type:
Article
Country of publication:
United States