Bile acid signaling in metabolic disease and drug therapy
Open accessAbstract
Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.
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Secondary bile acids antagonize the nuclear membrane farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5 in the intestines.
“Secondary bile acids antagonize the nuclear membrane farnesoid X receptor (FXR) and the G protein–coupled receptor TGR5103 in the intestines.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [103]
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The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders #
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Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
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Regulation of Intestinal Barrier Function by Microbial Metabolites
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Intestinal transport and metabolism of bile acids
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Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry
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Self-citationThe human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics
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The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
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Beneficial Bile Acid Metabolism from Lactobacillus plantarum of Food Origin
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Self-citationWhy cells need iron: a compendium of iron utilisation
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Bile acids activated receptors in inflammatory bowel disease
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The mechanism of berberine alleviating metabolic disorder based on gut microbiome
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“Bile acids can activate TGR5 and FXR receptors, regulate blood glucose, increase glycogen synthesis, inhibit liver glycogen synthesis, protect islet cell function and maintain blood glucose homeostasis (Li and Chiang, 2014).”
BackgroundLiu, L., Liu, Z., Li, H., Cao, Z., Li, W., Song, Z., Li, X., Lu, A., Lu, C., & Liu, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00012 · Cited by 68 · see citing works
New insights into microbial bile salt hydrolases: from physiological roles to potential applications
Dong, Z., Yang, S., Tang, C., Li, D., Kan, Y., & Yao, L. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1513541 · Cited by 64 · see citing works
Gallucci, G. M., Hayes, C. M., Boyer, J. L., Barbier, O., Assis, D. N., & Ghonem, N. S. (2024) · Cells · doi:10.3390/cells13151296 · Cited by 40 · see citing works
Functional and Phylogenetic Diversity of BSH and PVA Enzymes
Daly, J. W., Keely, S. J., & Gahan, C. G. M. (2021) · Microorganisms · doi:10.3390/microorganisms9040732 · Cited by 40 · see citing works
Interaction mechanisms between major depressive disorder and non-alcoholic fatty liver disease
Shao, Q., Wu, Y., Ji, J., Xu, T., Yu, Q., Ma, C., Liao, X., Cheng, F., & Wang, X. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.711835 · Cited by 32 · see citing works
[Retracted] A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction‐Related Diseases
Weng, Z.-B., Chen, Y.-R., Lv, J.-T., Wang, M.-X., Chen, Z.-Y., Zhou, W., Shen, X.-C., Zhan, L.-B., & Wang, F. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/4289383 · Cited by 32 · see citing works
“About 95% of BAs are actively ingested in the ileum through the apical sodium-dependent BA transporter (ASBT) at the tip of the brush edge of the small intestine and then enter the small intestinal epithelial cells [40, 41].”
RetractedFast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip
Byeon, J. H., Jung, D. J., Han, H.-J., Son, W.-C., & Jeong, G. S. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1452485 · Cited by 12 · see citing works
“The spatial heterogeneity in the liver serves a wide variety of physiological functions, including xenobiotic metabolism, protein and bile synthesis, and the dynamics of hepatic regeneration (Li and Chiang, 2014; Tanami et al., 2017).”
- Authors
- Li, T., & Chiang, J. Y. L.
- Affiliations
- University of Kansas Medical Center (US)
- Venue
- Pharmacological Reviews
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 66
- Issue
- 4
- Pages
- 948-983
- ISSN
- 0031-6997 (ISSN-L)
- PMC
- PMC4180336
- OpenAlex
- W2123561714
- Cited by
- 935
- References
- 435
- Citations by year
- 2026: 82 · 2025: 73 · 2024: 93 · 2023: 89 · 2022: 117 · 2021: 88 · 2020: 95 · 2019: 81 · 2018: 71 · 2017: 74 · 2016: 39 · 2015: 26 · 2014: 7
- FWCI
- 5.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pharmacological Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk044442-26, DK58379, DK44442)
- National Institute of General Medical Sciences (P20GM103549)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 58379, DK44442, R01-DK-044442, R01DK058379, R37DK058379, R01DK102487)
- National Center for Research Resources (P20RR021940)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- bile acids, bile acid signaling, farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, G protein-coupled bile acid receptor, bile acid synthesis, diurnal cycle, gut microbiota, non-alcoholic fatty liver disease, inflammatory bowel disease, diabetes mellitus, obesity, drug metabolism, metabolic disorders, bile acid derivatives
- MeSH terms
- Animals, Bile Acids and Salts, Circadian Rhythm, Glucose, Humans, Liver, Metabolic Diseases, Models, Biological, Signal Transduction, MicroRNAs, Receptors, G-Protein-Coupled, Lipid Metabolism, Microbiota
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