Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1016/j.isci.2023.107922
Licence creative commons licence
Title (Primary) A physiologically-based model of bile acid metabolism in mice
Author Kister, B.; Viehof, A.; Rolle-Kampczyk, U.; Schwentker, A.; Treichel, N.S.; Jennings, S.; Wirtz, T.H.; Blank, L.M.; Hornef, M.W.; von Bergen, M.; Clavel, T.; Kuepfer, L.
Source Titel iScience
Year 2023
Department iDiv; MOLSYB
Volume 26
Issue 10
Page From art. 107922
Language englisch
Topic T9 Healthy Planet
Supplements https://ars.els-cdn.com/content/image/1-s2.0-S2589004223019995-mmc1.pdf
Abstract Bile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking. Computational modeling may support functional analyses of the physiological processes involved in the EHC of BAs along the gut-liver axis. In this study, we developed a physiologically-based model of murine BA metabolism describing synthesis, hepatic and microbial transformations, systemic distribution, excretion and EHC of BAs at the whole-body level. For model development, BA metabolism of specific pathogen-free (SPF) mice was characterized in vivo by measuring BA levels and composition in various organs, expression of transporters along the gut and cecal microbiota composition. We found significantly different BA levels between male and female mice that could only be explained by adjusted expression of the hepatic enzymes and transporters in the model. Of note, this finding was in agreement with experimental observations. The model for SPF mice could also describe equivalent experimental data in germ-free mice by specifically switching off microbial activity in the intestine. The here presented model can therefore facilitate and guide functional analyses of BA metabolism in mice, e.g., the effect of pathophysiological alterations on BA metabolism and translation of results from mouse studies to a clinically relevant context through cross-species extrapolation.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=27977
Kister, B., Viehof, A., Rolle-Kampczyk, U., Schwentker, A., Treichel, N.S., Jennings, S., Wirtz, T.H., Blank, L.M., Hornef, M.W., von Bergen, M., Clavel, T., Kuepfer, L. (2023):
A physiologically-based model of bile acid metabolism in mice
iScience 26 (10), art. 107922