Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Open accessAbstract
Emerging evidence points to a strong association between the gut microbiota and the risk, development and progression of gastrointestinal cancers such as colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Bile acids, produced in the liver, are metabolized by enzymes derived from intestinal bacteria and are critically important for maintaining a healthy gut microbiota, balanced lipid and carbohydrate metabolism, insulin sensitivity and innate immunity. Given the complexity of bile acid signalling and the direct biochemical interactions between the gut microbiota and the host, a systems biology perspective is required to understand the liver-bile acid-microbiota axis and its role in gastrointestinal carcinogenesis to reverse the microbiota-mediated alterations in bile acid metabolism that occur in disease states. An examination of recent research progress in this area is urgently needed. In this Review, we discuss the mechanistic links between bile acids and gastrointestinal carcinogenesis in CRC and HCC, which involve two major bile acid-sensing receptors, farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5). We also highlight the strategies and cutting-edge technologies to target gut-microbiota-dependent alterations in bile acid metabolism in the context of cancer therapy.
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Gut bacteria produce a large array of metabolites that serve as important signaling factors and energy substrates, such as bile acids, choline, neurotransmitters, and short-chain fatty acids.
“These bacteria produce a large array of metabolites that serve as important signaling factors and energy substrates, such as bile acids (BA), choline, neurotransmitters, and short-chain fatty acids (SCFA) [213].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [213]
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“Although there is some controversy regarding the rank order of the FXR-activating potentials of bile acids, there is a consensus that unconjugated bile acids have greater potential to activate FXR than conjugated bile acids, possibly due to the greater lipophilicity of unconjugated bile acids (Jia et al., 2018).”
BackgroundSong, Z., Chen, J., Ji, Y., Yang, Q., Chen, Y., Wang, F., & Wu, Z. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124650 · Cited by 34 · see citing works
[Retracted] A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction‐Related Diseases
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“a “messenger” in the “gut-brain” axis [10, 11].”
RetractedImmunobiology of primary sclerosing cholangitis
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Bile resistance mechanisms in probiotics: From structural adaptation to metabolic regulation
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- Authors
- Jia, W., Xie, G., & Jia, W.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Jia, Wei
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2017-10-11
- Volume
- 15
- Issue
- 2
- Pages
- 111-128
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC5899973
- OpenAlex
- W2761145411
- Cited by
- 1,924
- References
- 215
- Citations by year
- 2026: 263 · 2025: 285 · 2024: 320 · 2023: 292 · 2022: 305 · 2021: 208 · 2020: 142 · 2019: 74 · 2018: 34
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U01CA188387, P30CA071789)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Keywords
- bile acids, gut microbiota, gastrointestinal inflammation, gastrointestinal carcinogenesis, colorectal cancer, hepatocellular carcinoma, farnesoid X receptor, TGR5, bile acid metabolism
- MeSH terms
- Gastrointestinal Microbiome, Bile Acids and Salts, Biological Transport, Digestive System Neoplasms, Gastroenteritis, Hepatitis, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Signal Transduction, Carcinogenesis
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