Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits
Abstract
Bilirubin, a metabolite derived from heme degradation, has traditionally been regarded as a waste product and a marker of liver injury. However, increasing evidence suggests that bilirubin also functions as a hormone, and reduced levels are associated with metabolic dysfunction. Studies have shown a strong association between low circulating bilirubin levels and an increased risk of metabolic disorders and cardiovascular disease. To advance bilirubin-based treatment strategies, it is essential to elucidate the mechanisms underlying bilirubin transport and metabolism. Therefore, we provide an in-depth discussion of bilirubin production and its subsequent fates, with a particular focus on the transport between the liver and the intestine. We describe the molecular players involved in heme degradation and biliverdin formation, leading to bilirubin production, followed by its transport from the bloodstream to hepatocytes and from the liver to the intestine. We discuss intestinal bilirubin catabolism, including the microbiome generation of urobilinogen, urobilin, and other metabolites. Finally, we discuss how bilirubin clearance and catabolism intersect with its metabolic effects, highlighting potential therapeutic targets. By integrating these aspects, this review provides a comprehensive understanding of bilirubin’s physiological importance, intestinal transport, and breakdown, as well as insights into novel strategies for treating hypobilirubinemia-associated disorders.
Document Type
Article
Publication Date
2025
Digital Object Identifier (DOI)
https://doi.org/10.3390/antiox14111326
Funding Information
This work was supported by the National Institutes of Health (NIH) R01DK121797 (T.D.H.J.), R01DA058933 (T.D.H.J.), R01HL174521 (T.D.H.J.), F31HL170972 (Z.A.K.), and a fellowship award from the American Heart Association for 25PRE1374495 (G.J.M.). The contents are solely the authors’ responsibility and do not necessarily represent the official views of the NIH.
Repository Citation
Kipp, Zachary A.; Pauss, Sally N.; Martinez, Genesee J.; Hinds, Jr., Terry D.; and Lee, Wang-Hsin, "Bilirubin Hepatic and Intestinal Transport and Catabolism: Physiology, Pathophysiology, and Benefits" (2025). Pharmacology and Nutritional Sciences Faculty Publications. 130.
https://uknowledge.uky.edu/pharmacol_facpub/130
Included in
Medical Nutrition Commons, Medical Pharmacology Commons, Pharmacology, Toxicology and Environmental Health Commons
Notes/Citation Information
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/ licenses/by/4.0/).