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Bile Acid Modifications at the Microbe-Host Interface: Potential for Nutraceutical and Pharmaceutical Interventions in Host Health
Open accessAbstract
Bile acids have emerged as important signaling molecules in the host, as they interact either locally or systemically with specific cellular receptors, in particular the farnesoid X receptor (FXR) and TGR5. These signaling functions influence systemic lipid and cholesterol metabolism, energy metabolism, immune homeostasis, and intestinal electrolyte balance. Through defined enzymatic activities, the gut microbiota can significantly modify the signaling properties of bile acids and therefore can have an impact upon host health. Alterations to the gut microbiota that influence bile acid metabolism are associated with metabolic disease, obesity, diarrhea, inflammatory bowel disease (IBD), Clostridium difficile infection, colorectal cancer, and hepatocellular carcinoma. Here, we examine the regulation of this gut-microbiota-liver axis in the context of bile acid metabolism and indicate how this pathway represents an important target for the development of new nutraceutical (diet and/or probiotics) and targeted pharmaceutical interventions.
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In the citing paper
“The expansion of microbial BSH activity has increased the diversity of bile acids in the host (Joyce and Gahan, 2016).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Joyce and Gahan, 2016
Experimental — accuracy not yet measuredIn the citing paper
“Microbially derived secondary bile acids are hypothesized to be interkingdom signaling molecules due to their ability to influence the composition and function of the gut microbiota as well as host physiology (407, 408).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [408]
In the citing paper
“Bile that is not re-absorbed in terminal small intestine undergoes further transformation by the intestinal microbiota (Joyce and Gahan, 2016).”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as Joyce and Gahan, 2016
In the citing paper
“Furthermore, Blautia and Bifidobacterium species are involved in the transformation of host bile.”
From Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism (2017) · cites this paper as Joyce and Gahan, 2016
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BSH-TRAP: Bile salt hydrolase tagging and retrieval with activity-based probes
Parasar, B., & Chang, P. V. (2022) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2021.12.002 · Cited by 6
“Bile acids (BAs) are a component of bile, which aids in the digestion and absorption of lipophilic nutrients in the intestines (Joyce and Gahan, 2016; Begley et al., 2005).”
BackgroundObesity and functional bowel disorders: are they linked?
Валерьевна, П. А., Romanitsa, A. I., & Rychkova, L. V. (2021) · Obesity and metabolism · doi:10.14341/omet12706 · Cited by 6
Metabolomic profiling for the preventive effects of dietary grape pomace against colorectal cancer
Wang, H., Tian, Q., Xu, Z., Du, ., & Zhu, M. J. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109308 · Cited by 8
Bracken, A. K., Malarney, K. P., & Chang, P. V. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.5c18912 · Cited by 5
Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acidPreprint
Oton, E. V., Volet, C., Jacquemin, N., Dong, Y., Hapfelmeier, S., Meibom, K. L., & Bernier‐Latmani, R. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.02.15.480494 · Cited by 5
Regulatory effect of Chinese Baijiu on gut microbiota and host metabolism
Fang, C., Wang, B., Han, Y., Zheng, X., Jia, W. P., Sun, J., & Xu, Y. (2025) · Food Research International · doi:10.1016/j.foodres.2025.117172 · Cited by 4
Chapela, S. P., Locatelli, J., Toral-Noristz, M., Saettone, F., Llobera, N. D., BASTIDAS, S., SÁNCHEZ, M., Arteaga-Pazmiño, C. L., Chedraui, P., Ceriani, F., et al. (2026) · Minerva Endocrinology · doi:10.23736/s2724-6507.25.04483-5 · Cited by 5
Bao, Y., Macelline, S. P., Selle, P. H., Chrystal, P. V., Wang, M., Liu, S. Y., Cao, A., & Toghyani, M. (2025) · Poultry Science · doi:10.1016/j.psj.2025.105107 · Cited by 4
“Certain intestinal bacteria express bile salt hydrolase enzymes that deconjugate the bile salts, liberating free primary bile acids (Joyce and Gahan, 2016).”
Qin, J., Wei, X., Cao, M., & Shi, B. (2023) · Animals · doi:10.3390/ani13213380 · Cited by 4
Shi, Y., Li, W., Fang, J., Ji, W., Cao, H., Yang, Y., & Gao, L. (2024) · Journal of Applied Toxicology · doi:10.1002/jat.4587 · Cited by 5
“Bile is secreted by the liver, and its main component is bile acids, which are the end products of cholesterol metabolism in the body (Joyce & Gahan, 2016).”
BackgroundTeng, T., Sun, G., Song, X., & Shi, B. (2022) · Journal of Animal Physiology and Animal Nutrition · doi:10.1111/jpn.13739 · Cited by 4
Neonatal diet impacts liver mitochondrial bioenergetics in piglets fed formula or human milk
Carvalho, E., Adams, S. H., Børsheim, E., Blackburn, M. L., Ono‐Moore, K. D., Cotter, M., Bowlin, A. K., & Yeruva, L. (2020) · BMC Nutrition · doi:10.1186/s40795-020-00338-7 · Cited by 5
Gut Microbiota Interactions With Dietary Terpenoids and Nitrogen-Containing Phytochemicals
García, C. J., Garcı́a-Villalba, R., Moreno, D. A., & Tomás-Barberán, F. A. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819265-8.00081-4 · Cited by 4
Zhang, B., Tian, M., Yahui, Y., Qiu, Y., Wang, L., Xiao, H., Zhu, X., Qin, L., Yang, X., & Jiang, Z. (2025) · Porcine Health Management · doi:10.1186/s40813-025-00440-x · Cited by 5
“CDCA is a main primary bile acid that naturally exists in human and animal bile [12].”
Gut microbiota and macrophage crosstalk: implications for colitis-associated colorectal cancer
Lyu, W., Zhang, Z., Liu, L., Sun, Y., Wang, B., Zhou, C., Liu, Z., & Feng, B. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1778244 · Cited by 3
“The accumulation of DCA has been established as a key initiating factor that drives aberrant activation and in fl ammation of colonic macrophages, and is closely associated with the pathogenesis of CRC (Ridlon et al., 2006; Cao et al., 2014; Joyce and Gahan, 2016; Zhao et al., 2016).”
Microbial Neuro-Immune Interactions and the Pathophysiology of IBD
Aguilera, M., & Melgar, S. (2016) · InTech eBooks · doi:10.5772/64832 · Cited by 4
“The latter one exacerbates colitis in IL‐10−/− mice and is known to respond to alterations in bile acid pro‐ files [201, 205].”
BackgroundNew Acquisitions Regarding Structure and Function of Intestinal Mucosal Barrier
Rossi, G. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.105463 · Cited by 4
Dietary Protein Source Mediates Colitis Pathogenesis Through Bacterial Modulation of Bile Acids
Gray, S. M., Wood, M. C., Mulkeen, S. C., Ahmed, S., Thaker, S. D., Chen, B., Sander, W. R., Bibeva, V., Zhang, X., Yang, J., et al. (2026) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2026.101825 · Cited by 2
Luo, F., Sun, L., Wan, R., Tian, Z., & He, Z. (2025) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2025.1616995 · Cited by 2
Microbial adaptation and host signaling: Bacteroides–bile acid interactions in gut health
Silva, C. M. G., Ferreira, R. B. R., & Lobo, L. A. (2026) · Anaerobe · doi:10.1016/j.anaerobe.2026.103041 · Cited by 2
Metagenomic analysis of bile acid biotransformation by gut microbiota in wild birds
Yang, M., Xie, L.-H., Wang, X., Gao, Y., Liu, R., Ma, H., Lei, C.-C., Jiang, J., Su, J., Zhang, X., et al. (2025) · Poultry Science · doi:10.1016/j.psj.2025.105956 · Cited by 2
“The critical nature of these functions underscores their potential as targets for nutraceutical and pharmaceutical interventions (Joyce and Gahan, 2016).”
Tian, Z., Luo, J., Yuan, W., Tan, L., Xu, C., Zhou, H., Li, M., Wu, Z. F., Zhao, W., Pan, D., et al. (2025) · Journal of Dairy Science · doi:10.3168/jds.2025-27005 · Cited by 2
Integrating bile acid metabolism into precision nutrition strategies for improved swine performance
Li, S., He, Y., Shaoyong, W., Wang, Y., & Jin, M. (2025) · Animal nutrition · doi:10.1016/j.aninu.2025.05.013 · Cited by 2
Zhang, T., Liu, H., Yuan, J., & Xie, B. (2025) · Food Research International · doi:10.1016/j.foodres.2025.118122 · Cited by 2
Zheng, S., Cheng, F.-E., Li, X., Du, H., Zhang, P., Zao, X., Ye, Y., & Shi, X. (2026) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2026.101490 · Cited by 2
Brown, B. I. (2019) · Gastrointestinal Disorders · doi:10.3390/gidisord1030027 · Cited by 2
“Similarly, gut microbiota influence colonic bile acid concentrations and metabolism, yet gut microbiota-targeted therapies, such as probiotics and prebiotics, have not yet been studied in the clinical management of BAD [153].”
BackgroundInfluentialBile acids as a diagnostic indicator of the state of homeostasis: a systematic descriptive analysis
Kuznetsov, Y. E., Lunegov, A. M., Ponamarev, V. S., & Romashova, E. B. (2022) · International Journal of Veterinary Medicine · doi:10.52419/issn2072-2419.2022.1.52 · Cited by 2
Keitel, V., Gertzen, C. G. W., Spomer, L., Gohlke, H., & Häussinger, D. (2020) · Wiley eBooks · doi:10.1002/9781119436812.ch24 · Cited by 2
Jin, Y., Hu, L., Wang, X., Bao, Z., Xu, Q., & Qian, M. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4108564 · Cited by 2
Zanella, D., Smith, N. K., Hardaway, J. A., Buchanan, A. M., Mullins, C. H., Galli, A., & Carter, A. M. (2023) · Scientific Reports · doi:10.1038/s41598-023-40456-3 · Cited by 1
Ouyang, Y., Jiang, W., Zhou, M., Yuan, E., Wang, M., & Ren, J. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.149620 · Cited by 1
Bile Acid Sequestration Attenuates Desulfovibrio-Induced Hepatic Injury
Yang, S., Zhou, L., Dong, J., Wang, S., Xue, Y., Ren, Y., & Geng, Y. (2025) · Microorganisms · doi:10.3390/microorganisms14010079 · Cited by 1
“They play a crucial role in the emulsification of lipids, their subsequent digestion and absorption, and the uptake of fat-soluble vitamins [24,25].”
The Jejunal Microbiota in Patients With Chronic Pancreatitis: Results From a Pilot Study
Sarkar, P., Sarkar, S., Unnisa, M., Singh, A. P., Inavolu, P., Rughwani, H., Jakkampudi, A., Jaggaiahgari, S., Reddy, D. N., & Talukdar, R. (2026) · Gastro Hep Advances · doi:10.1016/j.gastha.2026.100907 · Cited by 1
Anti-obesity effects of probiotics beyond BMI: a critical review of human clinical trials
Athapaththu, H. A. D., & Dey, G. (2026) · Letters in Applied Microbiology · doi:10.1093/lambio/ovag041 · Cited by 1
Metadata
- Authors
- Joyce, S. A., & Gahan, C. G. M.
- Affiliations
- APC Microbiome Institute (IE)
- University College Cork (IE)
- Venue
- Annual Review of Food Science and Technology
- Publisher
- Annual Reviews
- Published
- 2016-02-28
- Volume
- 7
- Issue
- 1
- Pages
- 313-333
- ISSN
- 1941-1421 (ISSN-L)
- 1941-1413
- OpenAlex
- W2152714616
- Cited by
- 241
- References
- 135
- Citations by year
- 2026: 27 · 2025: 22 · 2024: 27 · 2023: 20 · 2022: 37 · 2021: 24 · 2020: 20 · 2019: 16 · 2018: 15 · 2017: 23 · 2016: 10
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Food Science and Technology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland (SFI/12/RC/, 12/RC/2273, 12/RC/, SFI/12/RC/2273.)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- bile acids, gut microbiota, farnesoid X receptor, TGR5, bile acid metabolism, host-microbe interactions, probiotics, metabolic disorders, obesity, inflammatory bowel disease, Clostridium difficile infection, colorectal cancer, hepatocellular carcinoma, bile acid signaling
- MeSH terms
- Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Aging, Bile Acids and Salts, Diet, Disease, Energy Metabolism, Health Status, Humans, Liver, Technology, Pharmaceutical, Signal Transduction, Weight Gain, Receptors, Cytoplasmic and Nuclear, Dietary Supplements, Probiotics
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