TY - JOUR
T1 - The Hylemon-Björkhem pathway of bile acid 7-dehydroxylation
T2 - history, biochemistry, and microbiology
AU - Ridlon, Jason M.
AU - Daniel, Steven L.
AU - Gaskins, H. Rex
N1 - Funding Information:
The authors express their sincere appreciation to the following: 1) Ingemar Björkhem at the Karolinska Institutet in Stockholm, Sweden for the picture of himself and for providing helpful comments on the manuscript; 2) Phillip Hylemon at the Virginia Commonwealth University in Richmond for the picture of himself and for providing helpful comments on the manuscript; 3) the Lasker Awards Archives from the History of Medicine (IHM) at the National Library of Medicine for the picture of Sune Bergström; 4) the Karolinska Institutet and photographer Gunnar Ask for the picture of Bengt Samuelsson; 5) Elisabeth Norin at the Karolinska Institutet for the pictures of Tore Midtvedt and Bengt Gustafsson; 6) the late Alan Hofmann at the University of California, San Diego for the pictures of Erwin Mosbach, Jan Sjövall, Sven Lindstedt, and Henry Danielsson; 7) Elsevier for permitting us to reuse the picture of Alan Hofmann; 8) University of the Ryukyus in Okinawa, Japan for the picture of Fusae Takamine; 9) Anders Kallner at the Karolinska Institutet for the picture of himself; and 10) Carl Bokkenheuser for the picture of Victor Bokkenheuser. Figures were created with the software BioRender (https://www.biorender.com/). We would like to acknowledge financial support from National Institutes of Health grants (R01 CA204808-01 [J. M. R., H. R. G.], R01 GM134423-01A1 [J. M. R.], GM145920-01 [J. M. R], R03 AI147127-01A1 [J. M. R.]) as well as UIUC Department of Animal Sciences Matchstick grant and Hatch ILLU-538-916 (J. M. R.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
We would like to acknowledge financial support from National Institutes of Health grants (R01 CA204808-01 [J. M. R., H. R. G.], R01 GM134423-01A1 [J. M. R.], GM145920-01 [J. M. R], R03 AI147127-01A1 [J. M. R.]) as well as UIUC Department of Animal Sciences Matchstick grant and Hatch ILLU-538-916 (J. M. R.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2023 THE AUTHORS.
PY - 2023/8
Y1 - 2023/8
N2 - Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.
AB - Bile acids are detergents derived from cholesterol that function to solubilize dietary lipids, remove cholesterol from the body, and act as nutrient signaling molecules in numerous tissues with functions in the liver and gut being the best understood. Studies in the early 20th century established the structures of bile acids, and by mid-century, the application of gnotobiology to bile acids allowed differentiation of host-derived “primary” bile acids from “secondary” bile acids generated by host-associated microbiota. In 1960, radiolabeling studies in rodent models led to determination of the stereochemistry of the bile acid 7-dehydration reaction. A two-step mechanism was proposed, which we have termed the Samuelsson-Bergström model, to explain the formation of deoxycholic acid. Subsequent studies with humans, rodents, and cell extracts of Clostridium scindens VPI 12708 led to the realization that bile acid 7-dehydroxylation is a result of a multi-step, bifurcating pathway that we have named the Hylemon-Björkhem pathway. Due to the importance of hydrophobic secondary bile acids and the increasing measurement of microbial bai genes encoding the enzymes that produce them in stool metagenome studies, it is important to understand their origin.
KW - allo-bile acids
KW - bile acid dehydroxylation
KW - bile acids
KW - enterohepatic circulation
KW - gut microbiome
KW - intestinal lipid metabolism
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U2 - 10.1016/j.jlr.2023.100392
DO - 10.1016/j.jlr.2023.100392
M3 - Review article
C2 - 37211250
AN - SCOPUS:85168798957
SN - 0022-2275
VL - 64
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 8
M1 - 100392
ER -