Bile acids and the gut microbiota: metabolic interactions and impacts on disease

Collins, Stephanie L.; Stine, Jonathan G.; Bisanz, Jordan E.; Okafor, C. Denise; Patterson, Andrew D.

doi:10.1038/s41579-022-00805-x

Cited by 1,214Gut microbiota and healthDrug Transport and Resistance MechanismsCholesterol and Lipid Metabolism

Bile acids and the gut microbiota: metabolic interactions and impacts on disease

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Collins, Stephanie L., Stine, Jonathan G., Bisanz, Jordan E., Okafor, C. Denise, Patterson, Andrew D.·2023·Nature Reviews Microbiology

DOI 10.1038/s41579-022-00805-xPMC PMC12536349

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Abstract

Despite decades of bile acid research, diverse biological roles for bile acids have been discovered recently due to developments in understanding the human microbiota. As additional bacterial enzymes are characterized, and the tools used for identifying new bile acids become increasingly more sensitive, the repertoire of bile acids metabolized and/or synthesized by bacteria continues to grow. Additionally, bile acids impact microbiome community structure and function. In this Review, we highlight how the bile acid pool is manipulated by the gut microbiota, how it is dependent on the metabolic capacity of the bacterial community and how external factors, such as antibiotics and diet, shape bile acid composition. It is increasingly important to understand how bile acid signalling networks are affected in distinct organs where the bile acid composition differs, and how these networks impact infectious, metabolic and neoplastic diseases. These advances have enabled the development of therapeutics that target imbalances in microbiota-associated bile acid profiles.

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Bile acids are primarily synthesized by the liver from cholesterol, conjugated with taurine or glycine by BAAT, and released into the intestine.
“Bile acids (BAs) are an interesting candidate in this regard because they are primarily synthesized by the liver from cholesterol through a multistep process, conjugated with amino acids (taurine or glycine) by bile acid–CoA: amino acid N-acyltransferase (BAAT), and released into the intestine.”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [7]
The passage labeled Abstract (page unavailable) says primary bile acids are synthesized by hepatocytes from cholesterol, conjugated with glycine or taurine, and released into the duodenum. It does not identify BAAT as the enzyme responsible for conjugation, so that specific attribution is unsupported by our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Some conjugated bile acids are modified by gut microbes into secondary bile acids, and a portion recirculates to the liver and then to the bloodstream or back into bile.
“Some of these conjugated BAs are modified by gut microbes to form secondary BAs, with a portion of them recirculating back to the liver and eventually entering the bloodstream or being resecreted into bile (7).”
From Bile acid synthesis impedes tumor-specific T cell responses during liver cancer (2025) · cites this paper as [7]
The Abstract (page unavailable) says that gut microbes produce secondary bile acids and that bile acids are reabsorbed and recycled through enterohepatic circulation. The Bacterial metabolism of BAs section (page unavailable) describes deconjugation as a first step. Our copy does not establish the claimed onward route into the bloodstream or explicitly say that these secondary bile acids are resecreted into bile. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Non-reabsorbed primary bile acids are converted by the gut microbiota into secondary bile acids, deoxycholic acid and lithocholic acid, via deconjugation and dehydroxylation.
“However, non-reabsorbed primary BAs are converted by the gut microbiota into secondary BAs (deoxycholic acid, DCA, and lithocholic acid, LCA) via deconjugation and dehydroxylation, endowing them with new biological activities.20,350”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [20]

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Authors: Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D., & Patterson, A. D.
Affiliations: Pennsylvania State University (US)
Corresponding author: Patterson, Andrew D.
ORCID: Collins, Stephanie L.
Stine, Jonathan G.
Bisanz, Jordan E.
Okafor, C. Denise
Patterson, Andrew D.
Venue: Nature Reviews Microbiology
Publisher: Springer Science and Business Media LLC
Published: 2022-10-17
Volume: 21
Issue: 4
Pages: 236-247
ISSN: 1740-1526 (ISSN-L)
1740-1534
DOI: 10.1038/s41579-022-00805-x
PMC: PMC12536349
OpenAlex: W4306411778
Cited by: 1,214
References: 189
Citations by year: 2026: 408 · 2025: 425 · 2024: 287 · 2023: 93 · 2022: 1
FWCI: 21.14
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Microbiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R00AI147165)
National Institute of Diabetes and Digestive and Kidney Diseases (K23DK131290)
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 › Cholesterol and Lipid Metabolism
Keywords: bile acids, gut microbiota, bile acid metabolism, host-microbiota interactions, bile acid signaling, antibiotics, diet, obesity, colitis, cancer
MeSH terms: Gastrointestinal Microbiome, Bacteria, Bile Acids and Salts, Humans, Signal Transduction, Microbiota

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Bile acids and the gut microbiota: metabolic interactions and impacts on disease

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