Systemic gut microbial modulation of bile acid metabolism in host tissue compartments
Open accessAbstract
We elucidate the detailed effects of gut microbial depletion on the bile acid sub-metabolome of multiple body compartments (liver, kidney, heart, and blood plasma) in rats. We use a targeted ultra-performance liquid chromatography with time of flight mass-spectrometry assay to characterize the differential primary and secondary bile acid profiles in each tissue and show a major increase in the proportion of taurine-conjugated bile acids in germ-free (GF) and antibiotic (streptomycin/penicillin)-treated rats. Although conjugated bile acids dominate the hepatic profile (97.0 ± 1.5%) of conventional animals, unconjugated bile acids comprise the largest proportion of the total measured bile acid profile in kidney (60.0 ± 10.4%) and heart (53.0 ± 18.5%) tissues. In contrast, in the GF animal, taurine-conjugated bile acids (especially taurocholic acid and tauro-β-muricholic acid) dominated the bile acid profiles (liver: 96.0 ± 14.5%; kidney: 96 ± 1%; heart: 93 ± 1%; plasma: 93.0 ± 2.3%), with unconjugated and glycine-conjugated species representing a small proportion of the profile. Higher free taurine levels were found in GF livers compared with the conventional liver (5.1-fold; P < 0.001). Bile acid diversity was also lower in GF and antibiotic-treated tissues compared with conventional animals. Because bile acids perform important signaling functions, it is clear that these chemical communication networks are strongly influenced by microbial activities or modulation, as evidenced by farnesoid X receptor-regulated pathway transcripts. The presence of specific microbial bile acid co-metabolite patterns in peripheral tissues (including heart and kidney) implies a broader signaling role for these compounds and emphasizes the extent of symbiotic microbial influences in mammalian homeostasis.
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Bile acid composition varies dramatically between germ-free and control animals in feces, liver, heart, kidney, and plasma.
“the composition of bile acids varies dramatically between germ-free and control animals in feces, liver, heart, kidney and plasma (Duboc et al., 2013; Sayin et al., 2013; Swann et al., 2011).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Swann et al., 2011
The gut microbiome produces potent ligands corresponding to bile acid receptors.
“The gut microbiome produces potent ligands corresponding to BA receptors; probiotics or prebiotics could act as therapeutics of BA dysmetabolism, indicating that microbiota-targeted therapies could be effective in preventing and/or treating gut-related diseases, including AS (40).”
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“Indeed, the composition of bile acids varies dramatically between germ-free and control animals in feces, liver, heart, kidney, and plasma (Duboc et al., 2013; Sayin et al., 2013; Swann et al., 2011).”
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- Authors
- Swann, J. R., Want, E. J., Geier, F. M., Spagou, K., Wilson, I. D., Sidaway, J. E., Nicholson, J. K., & Holmes, E.
- Affiliations
- Imperial College London (GB)
- AstraZeneca, Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics; and
- AstraZeneca (United Kingdom) (GB)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-09-13
- Volume
- 108
- Issue
- supplement_1
- Pages
- 4523-4530
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3063584
- OpenAlex
- W2138546203
- Cited by
- 726
- References
- 68
- Citations by year
- 2026: 20 · 2025: 25 · 2024: 56 · 2023: 57 · 2022: 57 · 2021: 45 · 2020: 59 · 2019: 66 · 2018: 50 · 2017: 61 · 2016: 53 · 2015: 47 · 2014: 55 · 2013: 43 · 2012: 22
- FWCI
- 9.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- AstraZeneca
- Biotechnology and Biological Sciences Research Council (BB/C519670/1)
- 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 acid metabolism, gut microbiota, germ-free animals, taurine-conjugated bile acids, unconjugated bile acids, liver, kidney, heart, plasma, farnesoid X receptor, host-microbe signaling
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Anti-Bacterial Agents, Bacteria, Bile Acids and Salts, Chromatography, High Pressure Liquid, Heart, Kidney, Liver, Myocardium, Mass Spectrometry, Symbiosis, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Gastrointestinal Tract, Rats, Metagenome
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