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

Nature Reviews Microbiology volume 21, pages 236–247 (2023)Cite this article

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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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Fig. 1: Enterohepatic circulation of bile acids in humans.
Fig. 2: General bile acid structure.
Fig. 3: Factors affecting bacterial transformation of bile acids.
Fig. 4: Host and microbiota-dependent bile acid contributions to human disease.

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References

  1. Turnbaugh, P. J. et al. The Human Microbiome Project. Nature 449, 804–810 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fuchs, C. D. & Trauner, M. Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology. Nat. Rev. Gastroenterol. Hepatol. https://doi.org/10.1038/s41575-021-00566-7 (2022).

    Article  PubMed  Google Scholar 

  3. Hamilton, J. P. et al. Human cecal bile acids: concentration and spectrum. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G256–G263 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M. & Marchesi, J. R. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc. Natl Acad. Sci. USA 105, 13580–13585 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Hofmann, A. F. The enterohepatic circulation of bile acids in mammals: form and functions. Front. Biosci. 14, 2584–2598 (2009).

    Article  CAS  Google Scholar 

  6. Thakare, R., Alamoudi, J. A., Gautam, N., Rodrigues, A. D. & Alnouti, Y. Species differences in bile acids I. Plasma and urine bile acid composition. J. Appl. Toxicol. 38, 1323–1335 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Wahlström, A. et al. Induction of farnesoid X receptor signaling in germ-free mice colonized with a human microbiota. J. Lipid Res. 58, 412–419 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Li, J. & Dawson, P. A. Animal models to study bile acid metabolism. Biochim. Biophys. Acta 1865, 895–911 (2019).

    Article  CAS  Google Scholar 

  9. Honda, A. et al. Regulation of bile acid metabolism in mouse models with hydrophobic bile acid composition. J. Lipid Res. 61, 54–69 (2020).

    Article  CAS  PubMed  Google Scholar 

  10. Guzior, D. V. & Quinn, R. A. Review: microbial transformations of human bile acids. Microbiome 9, 140 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Foley, M. H. et al. Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization. Proc. Natl Acad. Sci. USA 118, e2017709118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Eldere, J. V., Celis, P., Pauw, G. D., Lesaffre, E. & Eyssen, H. Tauroconjugation of cholic acid stimulates 7 alpha-dehydroxylation by fecal bacteria. Appl. Environ. Microbiol. 62, 656–661 (1996).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Tanaka, H., Hashiba, H., Kok, J. & Mierau, I. Bile salt hydrolase of Bifidobacterium longum — biochemical and genetic characterization. Appl. Environ. Microbiol. 66, 2502–2512 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ridlon, J. M., Kang, D.-J. & Hylemon, P. B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47, 241–259 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. White, B. A., Lipsky, R. L., Fricke, R. J. & Hylemon, P. B. Bile acid induction specificity of 7α-dehydroxylase activity in an intestinal Eubacterium species. Steroids 35, 103–109 (1980).

    Article  CAS  PubMed  Google Scholar 

  16. Funabashi, M. et al. A metabolic pathway for bile acid dehydroxylation by the gut microbiome. Nature 582, 566–570 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Streidl, T. et al. The gut bacterium Extibacter muris produces secondary bile acids and influences liver physiology in gnotobiotic mice. Gut Microbes 13, 1–21 (2021).

    Article  PubMed  Google Scholar 

  18. Marion, S. et al. Biogeography of microbial bile acid transformations along the murine gut. J. Lipid Res. 61, 1450–1463 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wahlström, A., Sayin, S. I., Marschall, H.-U. & Bäckhed, F. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab. 24, 41–50 (2016).

    Article  PubMed  Google Scholar 

  20. Devlin, A. S. & Fischbach, M. A. A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11, 685–690 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Van Eldere, J., Robben, J., De Pauw, G., Merckx, R. & Eyssen, H. Isolation and identification of intestinal steroid-desulfating bacteria from rats and humans. Appl. Environ. Microbiol. 54, 2112–2117 (1988).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Korpela, J. T., Fotsis, T. & Adlercreutz, H. Multicomponent analysis of bile acids in faeces by anion exchange and capillary column gas-liquid chromatography: application in oxytetracycline treated subjects. J. Steroid Biochem. 25, 277–284 (1986).

    Article  CAS  PubMed  Google Scholar 

  23. Dawson, P. A. & Karpen, S. J. Intestinal transport and metabolism of bile acids. J. Lipid Res. 56, 1085–1099 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Quinn, R. A. et al. Global chemical impact of the microbiome includes novel bile acid conjugations. Nature 579, 123–129 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hoffmann, M. A. et al. High-confidence structural annotation of metabolites absent from spectral libraries. Nat. Biotechnol. 40, 411–421 (2022).

    Article  CAS  PubMed  Google Scholar 

  26. Gentry, E. et al. A synthesis-based reverse metabolomics approach for the discovery of chemical structures from humans and animals. Res. Sq. https://doi.org/10.21203/rs.3.rs-820302/v1 (2021).

    Article  Google Scholar 

  27. Wang, M. et al. Mass spectrometry searches using MASST. Nat. Biotechnol. 38, 19–26 (2020).

    Article  Google Scholar 

  28. Lucas, L. N. et al. Dominant bacterial phyla from the human gut show widespread ability to transform and conjugate bile acids. mSystems https://doi.org/10.1128/mSystems.00805-21 (2021).

    Article  PubMed  Google Scholar 

  29. Antunes, L. C. M. et al. Effect of antibiotic treatment on the intestinal metabolome. Antimicrob. Agents Chemother. 55, 1494–1503 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Swann, J. R. et al. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. Proc. Natl Acad. Sci. USA 108, 4523–4530 (2011).

    Article  CAS  PubMed  Google Scholar 

  31. Theriot, C. M. et al. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection. Nat. Commun. 5, 3114 (2014).

    Article  PubMed  Google Scholar 

  32. Vrieze, A. et al. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol. 60, 824–831 (2014).

    Article  CAS  PubMed  Google Scholar 

  33. Kuno, T., Hirayama-Kurogi, M., Ito, S. & Ohtsuki, S. Reduction in hepatic secondary bile acids caused by short-term antibiotic-induced dysbiosis decreases mouse serum glucose and triglyceride levels. Sci. Rep. 8, 1253 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Dethloff, F. et al. Paroxetine administration affects microbiota and bile acid levels in mice. Front. Psychiatry 11, 518 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Molina-Molina, E. et al. Exercising the hepatobiliary-gut axis. The impact of physical activity performance. Eur. J. Clin. Invest. 48, e12958 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ca, Y., Bj, M. & Jb, W. Chronic physical activity alters hepatobiliary excretory function in rats. J. Pharmacol. Exp. Ther. 265, 321–327 (1993).

    Google Scholar 

  37. Meissner, M. et al. Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice. Atherosclerosis 218, 323–329 (2011).

    Article  CAS  PubMed  Google Scholar 

  38. Wertheim, B. C. et al. Physical activity as a determinant of fecal bile acid levels. Cancer Epidemiol. Biomark. Prev. 18, 1591–1598 (2009).

    Article  CAS  Google Scholar 

  39. Danese, E. et al. Middle-distance running acutely influences the concentration and composition of serum bile acids: potential implications for cancer risk? Oncotarget 8, 52775–52782 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hughes, A. et al. Exercise training reverses gut dysbiosis in patients with biopsy-proven nonalcoholic steatohepatitis: a proof of concept study. Clin. Gastroenterol. Hepatol. 19, 1723–1725 (2021).

    Article  CAS  PubMed  Google Scholar 

  41. Wan, Y. et al. Unconjugated and secondary bile acid profiles in response to higher-fat, lower-carbohydrate diet and associated with related gut microbiota: a 6-month randomized controlled-feeding trial. Clin. Nutr. 39, 395–404 (2020).

    Article  CAS  PubMed  Google Scholar 

  42. Ellegård, L. & Andersson, H. Oat bran rapidly increases bile acid excretion and bile acid synthesis: an ileostomy study. Eur. J. Clin. Nutr. 61, 938–945 (2007).

    Article  PubMed  Google Scholar 

  43. Ellegård, L., Bosaeus, I. & Andersson, H. Will recommended changes in fat and fibre intake affect cholesterol absorption and sterol excretion? An ileostomy study. Eur. J. Clin. Nutr. 54, 306–313 (2000).

    Article  PubMed  Google Scholar 

  44. Louis, P., Hold, G. L. & Flint, H. J. The gut microbiota, bacterial metabolites and colorectal cancer. Nat. Rev. Microbiol. 12, 661–672 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. von Schwartzenberg, R. J. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595, 272–277 (2021).

    Article  Google Scholar 

  46. van Best, N. et al. Bile acids drive the newborn’s gut microbiota maturation. Nat. Commun. 11, 3692 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ridlon, J. M., Kang, D. J., Hylemon, P. B. & Bajaj, J. S. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 30, 332–338 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Sannasiddappa, T. H., Lund, P. A. & Clarke, S. R. In vitro antibacterial activity of unconjugated and conjugated bile salts on Staphylococcus aureus. Front. Microbiol. 8, 1581 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Tian, Y. et al. The microbiome modulating activity of bile acids. Gut Microbes 11, 979–996 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Begley, M., Gahan, C. G. M. & Hill, C. The interaction between bacteria and bile. FEMS Microbiol. Rev. 29, 625–651 (2005).

    Article  CAS  PubMed  Google Scholar 

  51. Miller, S. I. Antibiotic resistance and regulation of the Gram-negative bacterial outer membrane barrier by host innate immune molecules. mBio 7, e01541-16 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Thanassi, D. G., Cheng, L. W. & Nikaido, H. Active efflux of bile salts by Escherichia coli. J. Bacteriol. 179, 2512–2518 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liu, T., Zhang, L., Joo, D. & Sun, S.-C. NF-κB signaling in inflammation. Signal. Transduct. Target. Ther. 2, 17023 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Inagaki, T. et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl Acad. Sci. USA 103, 3920–3925 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Li, Y., Tang, R., Leung, P. S. C., Gershwin, M. E. & Ma, X. Bile acids and intestinal microbiota in autoimmune cholestatic liver diseases. Autoimmun. Rev. 16, 885–896 (2017).

    Article  CAS  PubMed  Google Scholar 

  56. Cabrera-Rubio, R., Patterson, A. M., Cotter, P. D. & Beraza, N. Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice. Sci. Rep. 9, 12324 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Rea, M. C. et al. Thuricin CD, a posttranslationally modified bacteriocin with a narrow spectrum of activity against Clostridium difficile. Proc. Natl Acad. Sci. USA 107, 9352–9357 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ng, K. M. et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 502, 96–99 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Theriot, C. M., Bowman, A. A. & Young, V. B. Antibiotic-induced alterations of the gut microbiota alter secondary bile acid production and allow for Clostridium difficile spore germination and outgrowth in the large intestine. mSphere 1, e00045-15 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Robinson, J. I. et al. Metabolomic networks connect host-microbiome processes to human Clostridioides difficile infections. J. Clin. Invest. 129, 3792–3806 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Sorg, J. A. & Sonenshein, A. L. Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol. 190, 2505–2512 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Thanissery, R., Winston, J. A. & Theriot, C. M. Inhibition of spore germination, growth, and toxin activity of clinically relevant C. difficile strains by gut microbiota derived secondary bile acids. Anaerobe 45, 86–100 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015).

    Article  CAS  PubMed  Google Scholar 

  64. Kang, J. D. et al. Bile acid 7α-dehydroxylating gut bacteria secrete antibiotics that inhibit Clostridium difficile: role of secondary bile acids. Cell Chem. Biol. 26, 27–34.e4 (2019).

    Article  CAS  PubMed  Google Scholar 

  65. Tam, J. et al. Intestinal bile acids directly modulate the structure and function of C. difficile TcdB toxin. Proc. Natl Acad. Sci. USA 117, 6792–6800 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Weingarden, A. R. et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G310–G319 (2014).

    Article  CAS  PubMed  Google Scholar 

  67. Louie, T. J. et al. Fidaxomicin versus vancomycin for Clostridium difficile infection. N. Engl. J. Med. 364, 422–431 (2011).

    Article  CAS  PubMed  Google Scholar 

  68. Qian, X. et al. Ridinilazole, a narrow spectrum antibiotic for treatment of Clostridioides difficile infection, enhances preservation of microbiota-dependent bile acids. Am. J. Physiol. Gastrointest. Liver Physiol. 319, G227–G237 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Franzosa, E. A. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat. Microbiol. 4, 293–305 (2019).

    Article  CAS  PubMed  Google Scholar 

  70. Manichanh, C. et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55, 205–211 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gevers, D. et al. The treatment-naïve microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Duboc, H. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62, 531–539 (2013).

    Article  CAS  PubMed  Google Scholar 

  73. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Heinken, A. et al. Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease. Microbiome 7, 75 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E. & Fiorucci, S. The bile acid receptor FXR is a modulator of intestinal innate immunity. J. Immunol. 183, 6251–6261 (2009).

    Article  CAS  PubMed  Google Scholar 

  77. Mencarelli, A. et al. Inhibition of NF-κB by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells. Eur. J. Pharmacol. 668, 317–324 (2011).

    Article  CAS  PubMed  Google Scholar 

  78. Gadaleta, R. M. et al. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut 60, 463–472 (2011).

    Article  CAS  PubMed  Google Scholar 

  79. Shah, Y. M., Ma, X., Morimura, K., Kim, I. & Gonzalez, F. J. Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-κB target gene expression. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G1114–G1122 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Wilson, A., Almousa, A., Teft, W. A. & Kim, R. B. Attenuation of bile acid-mediated FXR and PXR activation in patients with Crohn’s disease. Sci. Rep. 10, 1866 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Alberti, K. G. M. M. et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Xiao, J. et al. Prevalence of metabolic syndrome and its risk factors among rural adults in Nantong, China. Sci. Rep. 6, 38089 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

    Article  PubMed  Google Scholar 

  84. Bäckhed, F. et al. The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl Acad. Sci. USA 101, 15718–15723 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  85. Kootte, R. S. et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metab. 26, 611–619.e6 (2017).

    Article  CAS  PubMed  Google Scholar 

  86. Vrieze, A. et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143, 913–916.e7 (2012).

    Article  CAS  PubMed  Google Scholar 

  87. Pedersen, H. K. et al. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381 (2016).

    Article  CAS  PubMed  Google Scholar 

  88. He, Y. et al. Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis. Microbiome 6, 172 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article  CAS  PubMed  Google Scholar 

  90. Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).

    Article  CAS  PubMed  Google Scholar 

  91. Walters, W. A., Xu, Z. & Knight, R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 588, 4223–4233 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Bisanz, J. E., Upadhyay, V., Turnbaugh, J. A., Ly, K. & Turnbaugh, P. J. Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet. Cell Host Microbe 26, 265–272.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Jiao, N. et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD. Gut 67, 1881–1891 (2018).

    Article  CAS  PubMed  Google Scholar 

  95. Katsuma, S., Hirasawa, A. & Tsujimoto, G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem. Biophys. Res. Commun. 329, 386–390 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J. & Schoonjans, K. Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7, 678–693 (2008).

    Article  CAS  PubMed  Google Scholar 

  97. Pathak, P. et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology 68, 1574–1588 (2018).

    Article  CAS  PubMed  Google Scholar 

  98. Watanabe, M. et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Invest. 113, 1408–1418 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Joyce, S. A. et al. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc. Natl Acad. Sci. USA 111, 7421–7426 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ryan, K. K. et al. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509, 183–188 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Ðanić, M. et al. Pharmacological applications of bile acids and their derivatives in the treatment of metabolic syndrome. Front. Pharmacol. 9, 1382 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Zhang, H., Dong, M. & Liu, X. Obeticholic acid ameliorates obesity and hepatic steatosis by activating brown fat. Exp. Ther. Med. 22, 991 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Mudaliar, S. et al. Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. Gastroenterology 145, 574–582.e1 (2013).

    Article  CAS  PubMed  Google Scholar 

  104. Neuschwander-Tetri, B. A. et al. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385, 956–965 (2015).

    Article  CAS  PubMed  Google Scholar 

  105. Parséus, A. et al. Microbiota-induced obesity requires farnesoid X receptor. Gut 66, 429–437 (2017).

    Article  PubMed  Google Scholar 

  106. Zhang, Y. et al. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc. Natl Acad. Sci. USA 103, 1006–1011 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Watanabe, M. et al. Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure. J. Biol. Chem. 286, 26913–26920 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Ma, Y., Huang, Y., Yan, L., Gao, M. & Liu, D. Synthetic FXR agonist GW4064 prevents diet-induced hepatic steatosis and insulin resistance. Pharm. Res. 30, 1447–1457 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Jia, W., Xie, G. & Jia, W. Bile acid–microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 15, 111–128 (2018).

    Article  CAS  PubMed  Google Scholar 

  110. Cook, J. W., Kennaway, E. L. & Kennaway, N. M. Production of tumours in mice by deoxycholic acid. Nature 145, 627–627 (1940).

    Article  CAS  Google Scholar 

  111. McGarr, S. E., Ridlon, J. M. & Hylemon, P. B. Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J. Clin. Gastroenterol. 39, 98–109 (2005).

    PubMed  Google Scholar 

  112. Xie, G. et al. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis. Int. J. Cancer 139, 1764–1775 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Dapito, D. H. et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 21, 504–516 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Yoshimoto, S. et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97–101 (2013).

    Article  CAS  PubMed  Google Scholar 

  115. Bernstein, H., Bernstein, C., Payne, C. M., Dvorakova, K. & Garewal, H. Bile acids as carcinogens in human gastrointestinal cancers. Mutat. Res. 589, 47–65 (2005).

    Article  CAS  PubMed  Google Scholar 

  116. Grivennikov, S. I., Greten, F. R. & Karin, M. Immunity, inflammation, and cancer. Cell 140, 883–899 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Qiao, D., Gaitonde, S. V., Qi, W. & Martinez, J. D. Deoxycholic acid suppresses p53 by stimulating proteasome-mediated p53 protein degradation. Carcinogenesis 22, 957–964 (2001).

    Article  CAS  PubMed  Google Scholar 

  118. Payne, C. M., Bernstein, C., Dvorak, K. & Bernstein, H. Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis. Clin. Exp. Gastroenterol. 1, 19–47 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Washo-Stultz, D. et al. Role of mitochondrial complexes I and II, reactive oxygen species and arachidonic acid metabolism in deoxycholate-induced apoptosis. Cancer Lett. 177, 129–144 (2002).

    Article  CAS  PubMed  Google Scholar 

  120. Yu, J. et al. Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis. Cell Death Dis. 11, 640 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lax, S. et al. Expression of the nuclear bile acid receptor/farnesoid X receptor is reduced in human colon carcinoma compared to nonneoplastic mucosa independent from site and may be associated with adverse prognosis. Int. J. Cancer 130, 2232–2239 (2012).

    Article  CAS  PubMed  Google Scholar 

  122. Maran, R. R. M. et al. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J. Pharmacol. Exp. Ther. 328, 469–477 (2009).

    Article  CAS  PubMed  Google Scholar 

  123. Yang, F. et al. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res. 67, 863–867 (2007).

    Article  CAS  PubMed  Google Scholar 

  124. Wolfe, A. et al. Increased activation of the Wnt/β-catenin pathway in spontaneous hepatocellular carcinoma observed in farnesoid X receptor knockout mice. J. Pharmacol. Exp. Ther. 338, 12–21 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gadaleta, R. M. et al. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Biochim. Biophys. Acta Mol. Basis Dis. 1812, 851–858 (2011).

    Article  CAS  Google Scholar 

  126. Ridlon, J. M., Wolf, P. G. & Gaskins, H. R. Taurocholic acid metabolism by gut microbes and colon cancer. Gut Microbes 7, 201–215 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Laidlaw, S., Grosvenor, M. & Kopple, J. The taurine content of common foodstuffs. J. Parenter. Enter. Nutr. 14, 183–188 (1990).

    Article  CAS  Google Scholar 

  128. Reissig, C. J., Strain, E. C. & Griffiths, R. R. Caffeinated energy drinks — a growing problem. Drug. Alcohol. Depend. 99, 1–10 (2009).

    Article  CAS  PubMed  Google Scholar 

  129. van Nood, E. et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N. Engl. J. Med. 368, 407–415 (2013).

    Article  PubMed  Google Scholar 

  130. Seekatz, A. M. et al. Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection. Anaerobe 53, 64–73 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Mullish, B. H. et al. Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection. Gut 68, 1791–1800 (2019).

    Article  CAS  PubMed  Google Scholar 

  132. Paramsothy, S. et al. Specific bacteria and metabolites associated with response to fecal microbiota transplantation in patients with ulcerative colitis. Gastroenterology 156, 1440–1454.e2 (2019).

    Article  PubMed  Google Scholar 

  133. Zhao, L. et al. A Clostridia-rich microbiota enhances bile acid excretion in diarrhea-predominant irritable bowel syndrome. J. Clin. Invest. 130, 438–450 (2020).

    Article  CAS  PubMed  Google Scholar 

  134. Bárcena, C. et al. Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice. Nat. Med. 25, 1234–1242 (2019).

    Article  PubMed  Google Scholar 

  135. Kazemian, N. et al. The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome. Sci. Rep. 10, 18349 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Bibiloni, R. et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am. J. Gastroenterol. 100, 1539–1546 (2005).

    Article  PubMed  Google Scholar 

  137. Degirolamo, C., Rainaldi, S., Bovenga, F., Murzilli, S. & Moschetta, A. Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. Cell Rep. 7, 12–18 (2014).

    Article  CAS  PubMed  Google Scholar 

  138. Mencarelli, A. et al. Probiotics modulate intestinal expression of nuclear receptor and provide counter-regulatory signals to inflammation-driven adipose tissue activation. PLoS ONE 6, e22978 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Appleyard, C. B. et al. Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer. Am. J. Physiol. Gastrointest. Liver Physiol. 301, G1004–G1013 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Jones, M. L., Martoni, C. J. & Prakash, S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri NCIMB 30242: a randomized controlled trial. Eur. J. Clin. Nutr. 66, 1234–1241 (2012).

    Article  CAS  PubMed  Google Scholar 

  141. Alberts, D. S. et al. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J. Natl Cancer Inst. 97, 846–853 (2005).

    Article  CAS  PubMed  Google Scholar 

  142. Oyama, K., Shiota, G., Ito, H., Murawaki, Y. & Kawasaki, H. Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats. Carcinogenesis 23, 885–892 (2002).

    Article  CAS  PubMed  Google Scholar 

  143. Serfaty, L. et al. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology 38, 203–209 (2003).

    Article  CAS  PubMed  Google Scholar 

  144. Zhang, H., Xu, H., Zhang, C., Tang, Q. & Bi, F. Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis. Cell Death Discov. 7, 207 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Pearson, T. et al. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med. 8, 617–628 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Hang, S. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576, 143–148 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Adhikari, A. A. et al. A gut-restricted lithocholic acid analog as an inhibitor of gut bacterial bile salt hydrolases. ACS Chem. Biol. 16, 1401–1412 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Paik, D. et al. Human gut bacteria produce ΤΗ17-modulating bile acid metabolites. Nature 603, 907–912 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Song, X. et al. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature 577, 410–415 (2020).

    Article  CAS  PubMed  Google Scholar 

  150. van der Lelie, D. et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat. Commun. 12, 3105 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Wang, K. et al. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Rep. 26, 222–235.e5 (2019).

    Article  PubMed  Google Scholar 

  152. Nevens, F. et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N. Engl. J. Med. 375, 631–643 (2016).

    Article  CAS  PubMed  Google Scholar 

  153. Huijghebaert, S. M. & Eyssen, H. J. Specificity of bile salt sulfatase activity from Clostridium sp. strains S1. Appl. Environ. Microbiol. 44, 1030–1034 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Huijghebaert, S., Parmentier, G. & Eyssen, H. Specificity of bile salt sulfatase activity in man, mouse and rat intestinal microflora. J. Steroid Biochem. 20, 907–912 (1984).

    Article  CAS  PubMed  Google Scholar 

  155. Sayin, S. I. et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17, 225–235 (2013).

    Article  CAS  PubMed  Google Scholar 

  156. Thibaut, M. M. & Bindels, L. B. Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation. Trends Mol. Med. 28, 223–236 (2022).

    Article  CAS  PubMed  Google Scholar 

  157. Molinaro, A., Wahlström, A. & Marschall, H.-U. Role of bile acids in metabolic control. Trends Endocrinol. Metab. 29, 31–41 (2018).

    Article  CAS  PubMed  Google Scholar 

  158. Makishima, M. et al. Identification of a nuclear receptor for bile acids. Science 284, 1362–1365 (1999).

    Article  CAS  PubMed  Google Scholar 

  159. Parks, D. J. et al. Bile acids: natural ligands for an orphan nuclear receptor. Science 284, 1365–1368 (1999).

    Article  CAS  PubMed  Google Scholar 

  160. Inagaki, T. et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2, 217–225 (2005).

    Article  CAS  PubMed  Google Scholar 

  161. Holt, J. A. et al. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 17, 1581–1591 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Goodwin, B. et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6, 517–526 (2000).

    Article  CAS  PubMed  Google Scholar 

  163. Lu, T. T. et al. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6, 507–515 (2000).

    Article  CAS  PubMed  Google Scholar 

  164. Sinal, C. J. et al. Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102, 731–744 (2000).

    Article  CAS  PubMed  Google Scholar 

  165. Sanyal, S. et al. Involvement of corepressor complex subunit GPS2 in transcriptional pathways governing human bile acid biosynthesis. Proc. Natl Acad. Sci. USA 104, 15665–15670 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Pircher, P. C. et al. Farnesoid X receptor regulates bile acid-amino acid conjugation. J. Biol. Chem. 278, 27703–27711 (2003).

    Article  CAS  PubMed  Google Scholar 

  167. Stedman, C. A. M. et al. Nuclear receptors constitutive androstane receptor and pregnane X receptor ameliorate cholestatic liver injury. Proc. Natl Acad. Sci. USA 102, 2063–2068 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Saini, S. P. S. et al. A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol. Pharmacol. 65, 292–300 (2004).

    Article  CAS  PubMed  Google Scholar 

  169. Makishima, M. et al. Vitamin D receptor as an intestinal bile acid sensor. Science 296, 1313–1316 (2002).

    Article  CAS  PubMed  Google Scholar 

  170. Sonoda, J. et al. Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR). Proc. Natl Acad. Sci. USA 99, 13801–13806 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Staudinger, J. L. et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl Acad. Sci. USA 98, 3369–3374 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. McCarthy, T. C., Li, X. & Sinal, C. J. Vitamin D receptor-dependent regulation of colon multidrug resistance-associated protein 3 gene expression by bile acids. J. Biol. Chem. 280, 23232–23242 (2005).

    Article  CAS  PubMed  Google Scholar 

  173. Schmidt, D. R. et al. Regulation of bile acid synthesis by fat-soluble vitamins A and D. J. Biol. Chem. 285, 14486–14494 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Bhalla, S., Ozalp, C., Fang, S., Xiang, L. & Kemper, J. K. Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1α: functional implications in hepatic cholesterol and glucose metabolism. J. Biol. Chem. 279, 45139–45147 (2004).

    Article  CAS  PubMed  Google Scholar 

  175. Miao, J., Fang, S., Bae, Y. & Kemper, J. K. Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. J. Biol. Chem. 281, 14537–14546 (2006).

    Article  CAS  PubMed  Google Scholar 

  176. Maruyama, T. et al. Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 298, 714–719 (2002).

    Article  CAS  PubMed  Google Scholar 

  177. Kawamata, Y. et al. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278, 9435–9440 (2003).

    Article  CAS  PubMed  Google Scholar 

  178. Wang, Y.-D., Chen, W.-D., Yu, D., Forman, B. M. & Huang, W. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor κ light-chain enhancer of activated B cells (NF-κB) in mice. Hepatol. Baltim. Md. 54, 1421–1432 (2011).

    Article  CAS  Google Scholar 

  179. Alemi, F. et al. The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice. Gastroenterology 144, 145–154 (2013).

    Article  CAS  PubMed  Google Scholar 

  180. Thomas, C. et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10, 167–177 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Watanabe, M. et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439, 484–489 (2006).

    Article  CAS  PubMed  Google Scholar 

  182. Meixiong, J., Vasavda, C., Snyder, S. H. & Dong, X. MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus. Proc. Natl Acad. Sci. USA 116, 10525–10530 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Yu, H. et al. MRGPRX4 is a bile acid receptor for human cholestatic itch. eLife 8, e48431 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  184. Cao, C. et al. Structure, function and pharmacology of human itch GPCRs. Nature 600, 170–175 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA

    Stephanie L. Collins, Jordan E. Bisanz, C. Denise Okafor & Andrew D. Patterson

  2. Division of Gastroenterology and Hepatology, Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Jonathan G. Stine

  3. Department of Public Health Sciences, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Jonathan G. Stine

  4. Penn State Health Liver Center, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Jonathan G. Stine

  5. Penn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA

    Jonathan G. Stine

  6. Department of Chemistry, The Pennsylvania State University, University Park, PA, USA

    C. Denise Okafor

  7. Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA, USA

    Andrew D. Patterson

  8. Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, USA

    Andrew D. Patterson

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S.L.C. researched data for the article. All authors contributed to discussion of the content, and reviewed and edited the manuscript before submission. S.L.C., C.D.O., A.D.P. and J.G.S. wrote the article.

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Glossary

Amphipathic

Containing both hydrophilic (polar) and hydrophobic (nonpolar) regions.

Micelles

A collection or aggregate of amphipathic molecules that self-assemble in aqueous solution so that the hydrophobic portions are shielded from water.

Cholestasis

A liver disease characterized by blockage of or reduced bile flow.

Brown fat

Adipose tissue containing high numbers of mitochondria, involved in metabolizing energy sources to produce heat.

Pouchitis

Inflammation of the J-pouch in surgery for ulcerative colitis.

J-pouch

A J-shaped surgical reformation of the ileum, connected directly to the anus after the removal of diseased colon in patients with ulcerative colitis.

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Collins, S.L., Stine, J.G., Bisanz, J.E. et al. Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat Rev Microbiol 21, 236–247 (2023). https://doi.org/10.1038/s41579-022-00805-x

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