The DOI matches its Crossref record; 699 of the 699 references it cites were found in a registry or an index.
Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets
Open accessAbstract
Bile acids, once considered mere dietary surfactants, now emerge as critical modulators of macronutrient (lipid, carbohydrate, protein) metabolism and the systemic pro-inflammatory/anti-inflammatory balance. Bile acid metabolism and signaling pathways play a crucial role in protecting against, or if aberrant, inducing cardiometabolic, inflammatory, and neoplastic conditions, strongly influencing health and disease. No curative treatment exists for any bile acid influenced disease, while the most promising and well-developed bile acid therapeutic was recently rejected by the FDA. Here, we provide a bottom-up approach on bile acids, mechanistically explaining their biochemistry, physiology, and pharmacology at canonical and non-canonical receptors. Using this mechanistic model of bile acids, we explain how abnormal bile acid physiology drives disease pathogenesis, emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic diseases. We provide an in-depth summary on pre-existing bile acid receptor modulators, explain their shortcomings, and propose solutions for how they may be remedied. Lastly, we rationalize novel targets for further translational drug discovery and provide future perspectives. Rather than dismissing bile acid therapeutics due to recent setbacks, we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.
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Akkız, H., Gieseler, R. K., & Canbay, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147873 · Cited by 191
Gut microbial metabolites in cancer therapy
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Microbiome−mediated crosstalk between T2DM and MASLD: a translational review focused on function
Jing, M., & Jiang, Y. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1677175 · Cited by 24
Carotenoids Improve Obesity and Fatty Liver Disease via Gut Microbiota: A Narrative Review
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“Bile acids (BAs) are a large family of molecules that hepat-ically synthesize cholesterol derivatives (Fleishman and Kumar 2024).”
Metadata
- Authors
- Fleishman, J. S., & Kumar, S.
- Venue
- Signal Transduction and Targeted Therapy
- Published
- 2024-04-26
- Volume
- 9
- Issue
- 1
- Pages
- 97-97
- ISSN
- 2059-3635 (ISSN-L)
- OpenAlex
- W4395445997
- Cited by
- 544
- References
- 699
- FWCI
- 83.49
- Type
- journal article
- Language
- en
- Open access
- gold
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- Fleishman, J. S., & Kumar, S. (2024). Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets. Signal Transduction and Targeted Therapy. https://doi.org/10.1038/s41392-024-01811-6
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