Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism

Cell Metabolism

Volumn 24, Issue 1, 2016, Pages 41-50

  Wahlström, Annika ^a   Sayin, Sama I ^a   Marschall, Hanns Ulrich ^a   Bäckhed, Fredrik ^a,b  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b Capital Region   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

BILE ACID; FARNESOID X RECEPTOR; G PROTEIN COUPLED MEMBRANE RECEPTOR 5; UNCLASSIFIED DRUG; CELL RECEPTOR; FARNESOID X-ACTIVATED RECEPTOR;

BARIATRIC SURGERY; BILE ACID METABOLISM; BILE ACID SYNTHESIS; HUMAN; INTESTINE FLORA; INTESTINE FUNCTION; METABOLIC DISORDER; MICROBIAL METABOLISM; MULTICENTER STUDY (TOPIC); NONALCOHOLIC FATTY LIVER; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANIMAL; DIET; INTESTINE; METABOLISM; MICROBIOLOGY; MICROFLORA;

ANIMALS; BARIATRIC SURGERY; BILE ACIDS AND SALTS; DIET; HUMANS; INTESTINES; MICROBIOTA; RECEPTORS, CYTOPLASMIC AND NUCLEAR;

EID: 84991053856     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2016.05.005     Document Type: Review

References (120)

1. Archer, R.H., Chong, R., Maddox, I.S., Hydrolysis of bile acid conjugates by clostridium bifermentans. Eur. J. Appl. Microbiol. 14 (1982), 41–45.
2. Aron-Wisnewsky, J., Clément, K., The gut microbiome, diet, and links to cardiometabolic and chronic disorders. Nat. Rev. Nephrol. 12 (2016), 169–181.
3. Arora, T., Bäckhed, F., The gut microbiota and metabolic disease: current understanding and future perspectives. J. Intern Med., 2016, 10.1111/joim.12508 Published online April 12, 2016.
4. Bäckhed, F., Ding, H., Wang, T., Hooper, L.V., Koh, G.Y., Nagy, A., Semenkovich, C.F., Gordon, J.I., The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. U S A 101 (2004), 15718–15723.
5. Baron, E.J., Summanen, P., Downes, J., Roberts, M.C., Wexler, H., Finegold, S.M., Bilophila wadsworthia, gen. nov. and sp. nov., a unique gram-negative anaerobic rod recovered from appendicitis specimens and human faeces. J. Gen. Microbiol. 135 (1989), 3405–3411.
6. Bennett, B.J., de Aguiar Vallim, T.Q., Wang, Z., Shih, D.M., Meng, Y., Gregory, J., Allayee, H., Lee, R., Graham, M., Crooke, R., et al. Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metab. 17 (2013), 49–60.
7. Beuers, U., Fischer, S., Spengler, U., Paumgartner, G., Formation of iso-ursodeoxycholic acid during administration of ursodeoxycholic acid in man. J. Hepatol. 13 (1991), 97–103.
8. Broeders, E.P., Nascimento, E.B., Havekes, B., Brans, B., Roumans, K.H., Tailleux, A., Schaart, G., Kouach, M., Charton, J., Deprez, B., et al. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity. Cell Metab. 22 (2015), 418–426.
9. Caesar, R., Tremaroli, V., Kovatcheva-Datchary, P., Cani, P.D., Bäckhed, F., Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab. 22 (2015), 658–668.
10. Carr, R.M., Reid, A.E., FXR agonists as therapeutic agents for non-alcoholic fatty liver disease. Curr. Atheroscler. Rep., 17, 2015, 500.
11. Chen, X., Lou, G., Meng, Z., Huang, W., TGR5: a novel target for weight maintenance and glucose metabolism. Exp. Diabetes Res., 2011, 2011, 853501.
12. Clements, W.D., Parks, R., Erwin, P., Halliday, M.I., Barr, J., Rowlands, B.J., Role of the gut in the pathophysiology of extrahepatic biliary obstruction. Gut 39 (1996), 587–593.
13. Danielsson, H., Eneroth, P., Hellstrom, K., Sjovall, J., Synthesis of some 3beta-hydroxylated bile acids and the isolation of 3beta, 12alpha-dihydroxy-5beta-cholanic acid from feces. J. Biol. Chem. 237 (1962), 3657–3659.
14. David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., Ling, A.V., Devlin, A.S., Varma, Y., Fischbach, M.A., et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505 (2014), 559–563.
15. de Aguiar Vallim, T.Q., Tarling, E.J., Edwards, P.A., Pleiotropic roles of bile acids in metabolism. Cell Metab. 17 (2013), 657–669.
16. 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 (2014), 12–18.
17. Devkota, S., Chang, E.B., Interactions between diet, bile acid metabolism, gut microbiota, and inflammatory bowel diseases. Dig. Dis. 33 (2015), 351–356.
18. Devkota, S., Wang, Y., Musch, M.W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D.A., Jabri, B., Chang, E.B., Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature 487 (2012), 104–108.
19. Devlin, A.S., Fischbach, M.A., A biosynthetic pathway for a prominent class of microbiota-derived bile acids. Nat. Chem. Biol. 11 (2015), 685–690.
20. Doerner, K.C., Takamine, F., LaVoie, C.P., Mallonee, D.H., Hylemon, P.B., Assessment of fecal bacteria with bile acid 7 alpha-dehydroxylating activity for the presence of bai-like genes. Appl. Environ. Microbiol. 63 (1997), 1185–1188.
21. Downes, M., Verdecia, M.A., Roecker, A.J., Hughes, R., Hogenesch, J.B., Kast-Woelbern, H.R., Bowman, M.E., Ferrer, J.L., Anisfeld, A.M., Edwards, P.A., et al. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol. Cell 11 (2003), 1079–1092.
22. El-Mir, M.Y., Badia, M.D., Luengo, N., Monte, M.J., Marin, J.J., Increased levels of typically fetal bile acid species in patients with hepatocellular carcinoma. Clin. Sci. 100 (2001), 499–508.
23. Eyssen, H., De Pauw, G., Stragier, J., Verhulst, A., Cooperative formation of omega-muricholic acid by intestinal microorganisms. Appl. Environ. Microbiol. 45 (1983), 141–147.
24. Falany, C.N., Johnson, M.R., Barnes, S., Diasio, R.B., Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA:amino acid N-acyltransferase. J. Biol. Chem. 269 (1994), 19375–19379.
25. Falany, C.N., Fortinberry, H., Leiter, E.H., Barnes, S., Cloning, expression, and chromosomal localization of mouse liver bile acid CoA:amino acid N-acyltransferase. J. Lipid Res. 38 (1997), 1139–1148.
26. Fang, S., Suh, J.M., Reilly, S.M., Yu, E., Osborn, O., Lackey, D., Yoshihara, E., Perino, A., Jacinto, S., Lukasheva, Y., et al. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat. Med. 21 (2015), 159–165.
27. Flynn, C.R., Albaugh, V.L., Cai, S., Cheung-Flynn, J., Williams, P.E., Brucker, R.M., Bordenstein, S.R., Guo, Y., Wasserman, D.H., Abumrad, N.N., Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat. Commun., 6, 2015, 7715.
28. Fukiya, S., Arata, M., Kawashima, H., Yoshida, D., Kaneko, M., Minamida, K., Watanabe, J., Ogura, Y., Uchida, K., Itoh, K., et al. Conversion of cholic acid and chenodeoxycholic acid into their 7-oxo derivatives by Bacteroides intestinalis AM-1 isolated from human feces. FEMS Microbiol. Lett. 293 (2009), 263–270.
29. Gilliland, S.E., Speck, M.L., Deconjugation of bile acids by intestinal lactobacilli. Appl. Environ. Microbiol. 33 (1977), 15–18.
30. Gonzalez, F.J., Jiang, C., Bisson, W.H., Patterson, A.D., Inhibition of farnesoid X receptor signaling shows beneficial effects in human obesity. J. Hepatol. 62 (2015), 1234–1236.
31. Goodwin, B., Jones, S.A., Price, R.R., Watson, M.A., McKee, D.D., Moore, L.B., Galardi, C., Wilson, J.G., Lewis, M.C., Roth, M.E., et al. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell 6 (2000), 517–526.
32. Gustafsson, B.E., Bergstrom, S., Lindstedt, S., Norman, A., Turnover and nature of fecal bile acids in germfree and infected rats fed cholic acid-24-14C; bile acids and steroids 41. Proc. Soc. Exp. Biol. Med. 94 (1957), 467–471.
33. Gustafsson, B.E., Angelin, B., Björkhem, I., Einarsson, K., Gustafsson, J.A., Effects of feeding chenodeoxycholic acid on metabolism of cholesterol and bile acids in germ-free rats. Lipids 16 (1981), 228–233.
34. Hamilton, J.P., Xie, G., Raufman, J.P., Hogan, S., Griffin, T.L., Packard, C.A., Chatfield, D.A., Hagey, L.R., Steinbach, J.H., Hofmann, A.F., Human cecal bile acids: concentration and spectrum. Am. J. Physiol. Gastrointest. Liver Physiol. 293 (2007), G256–G263.
35. Hanniman, E.A., Lambert, G., McCarthy, T.C., Sinal, C.J., Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice. J. Lipid Res. 46 (2005), 2595–2604.
36. Hirano, S., Masuda, N., Epimerization of the 7-hydroxy group of bile acids by the combination of two kinds of microorganisms with 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activity, respectively. J. Lipid Res. 22 (1981), 1060–1068.
37. Hirano, S., Masuda, N., Transformation of bile acids by Eubacterium lentum. Appl. Environ. Microbiol. 42 (1981), 912–915.
38. Hirano, S., Masuda, N., Oda, H., Mukai, H., Transformation of bile acids by Clostridium perfringens. Appl. Environ. Microbiol. 42 (1981), 394–399.
39. Hofmann, A.F., Hagey, L.R., Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell. Mol. Life Sci. 65 (2008), 2461–2483.
40. Holmes, E., Li, J.V., Marchesi, J.R., Nicholson, J.K., Gut microbiota composition and activity in relation to host metabolic phenotype and disease risk. Cell Metab. 16 (2012), 559–564.
41. Hylemon, P.B., Melone, P.D., Franklund, C.V., Lund, E., Björkhem, I., Mechanism of intestinal 7 alpha-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product. J. Lipid Res. 32 (1991), 89–96.
42. Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C.L., McDonald, J.G., Luo, G., Jones, S.A., Goodwin, B., Richardson, J.A., et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2 (2005), 217–225.
43. Inagaki, T., Moschetta, A., Lee, Y.K., Peng, L., Zhao, G., Downes, M., Yu, R.T., Shelton, J.M., Richardson, J.A., Repa, J.J., et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc. Natl. Acad. Sci. U S A 103 (2006), 3920–3925.
44. Jansen, P.L., van Werven, J., Aarts, E., Berends, F., Janssen, I., Stoker, J., Schaap, F.G., Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery. Dig. Dis. 29 (2011), 48–51.
45. Jiang, C., Xie, C., Li, F., Zhang, L., Nichols, R.G., Krausz, K.W., Cai, J., Qi, Y., Fang, Z.Z., Takahashi, S., et al. Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease. J. Clin. Invest. 125 (2015), 386–402.
46. Jiang, C., Xie, C., Lv, Y., Li, J., Krausz, K.W., Shi, J., Brocker, C.N., Desai, D., Amin, S.G., Bisson, W.H., et al. Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction. Nat. Commun., 6, 2015, 10166.
47. Jones, B.V., Begley, M., Hill, C., Gahan, C.G., Marchesi, J.R., Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc. Natl. Acad. Sci. U S A 105 (2008), 13580–13585.
48. Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., et al. A G protein-coupled receptor responsive to bile acids. J. Biol. Chem. 278 (2003), 9435–9440.
49. Kellogg, T.F., Wostmann, B.S., Fecal neutral steroids and bile acids from germfree rats. J. Lipid Res. 10 (1969), 495–503.
50. Kellogg, T.F., Knight, P.L., Wostmann, B.S., Effect of bile acid deconjugation on the fecal excretion of steroids. J. Lipid Res. 11 (1970), 362–366.
51. Kim, I., Ahn, S.H., Inagaki, T., Choi, M., Ito, S., Guo, G.L., Kliewer, S.A., Gonzalez, F.J., Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J. Lipid Res. 48 (2007), 2664–2672.
52. Kisiela, M., Skarka, A., Ebert, B., Maser, E., Hydroxysteroid dehydrogenases (HSDs) in bacteria: a bioinformatic perspective. J. Steroid Biochem. Mol. Biol. 129 (2012), 31–46.
53. Kitahara, M., Takamine, F., Imamura, T., Benno, Y., Assignment of Eubacterium sp. VPI 12708 and related strains with high bile acid 7alpha-dehydroxylating activity to Clostridium scindens and proposal of Clostridium hylemonae sp. nov., isolated from human faeces. Int. J. Syst. Evol. Microbiol. 50 (2000), 971–978.
54. Kitahara, M., Takamine, F., Imamura, T., Benno, Y., Clostridium hiranonis sp. nov., a human intestinal bacterium with bile acid 7alpha-dehydroxylating activity. Int. J. Syst. Evol. Microbiol. 51 (2001), 39–44.
55. Koeth, R.A., Wang, Z., Levison, B.S., Buffa, J.A., Org, E., Sheehy, B.T., Britt, E.B., Fu, X., Wu, Y., Li, L., et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19 (2013), 576–585.
56. Kong, B., Wang, L., Chiang, J.Y., Zhang, Y., Klaassen, C.D., Guo, G.L., Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology 56 (2012), 1034–1043.
57. Koopman, J.P., Kennis, H.M., Lankhorst, A., Welling, G.W., Hectors, M.P., Nagengast, F., ‘Normalization’ of germfree mice after direct and indirect contact with mice having a ‘normal’ intestinal microflora. Lab. Anim. 20 (1986), 286–290.
58. Kuipers, F., Bloks, V.W., Groen, A.K., Beyond intestinal soap–bile acids in metabolic control. Nat. Rev. Endocrinol. 10 (2014), 488–498.
59. Lambert, G., Amar, M.J., Guo, G., Brewer, H.B. Jr., Gonzalez, F.J., Sinal, C.J., The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J. Biol. Chem. 278 (2003), 2563–2570.
60. Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., Staels, B., Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev. 89 (2009), 147–191.
61. Li, F., Jiang, C., Krausz, K.W., Li, Y., Albert, I., Hao, H., Fabre, K.M., Mitchell, J.B., Patterson, A.D., Gonzalez, F.J., Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat. Commun., 4, 2013, 2384.
62. Li-Hawkins, J., Gåfvels, M., Olin, M., Lund, E.G., Andersson, U., Schuster, G., Björkhem, I., Russell, D.W., Eggertsen, G., Cholic acid mediates negative feedback regulation of bile acid synthesis in mice. J. Clin. Invest. 110 (2002), 1191–1200.
63. Lorenzo-Zúñiga, V., Bartolí, R., Planas, R., Hofmann, A.F., Viñado, B., Hagey, L.R., Hernández, J.M., Mañé, J., Alvarez, M.A., Ausina, V., Gassull, M.A., Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 37 (2003), 551–557.
64. Lu, T.T., Makishima, M., Repa, J.J., Schoonjans, K., Kerr, T.A., Auwerx, J., Mangelsdorf, D.J., Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol. Cell 6 (2000), 507–515.
65. Ma, K., Saha, P.K., Chan, L., Moore, D.D., Farnesoid X receptor is essential for normal glucose homeostasis. J. Clin. Invest. 116 (2006), 1102–1109.
66. MacDonald, I.A., Rochon, Y.P., Hutchison, D.M., Holdeman, L.V., Formation of ursodeoxycholic acid from chenodeoxycholic acid by a 7 beta-hydroxysteroid dehydrogenase-elaborating Eubacterium aerofaciens strain cocultured with 7 alpha-hydroxysteroid dehydrogenase-elaborating organisms. Appl. Environ. Microbiol. 44 (1982), 1187–1195.
67. Macdonald, I.A., White, B.A., Hylemon, P.B., Separation of 7 alpha- and 7 beta-hydroxysteroid dehydrogenase activities from clostridium absonum ATCC# 27555 and cellular response of this organism to bile acid inducers. J. Lipid Res. 24 (1983), 1119–1126.
68. Madsen, D., Beaver, M., Chang, L., Bruckner-Kardoss, E., Wostmann, B., Analysis of bile acids in conventional and germfree rats. J. Lipid Res. 17 (1976), 107–111.
69. Makishima, M., Okamoto, A.Y., Repa, J.J., Tu, H., Learned, R.M., Luk, A., Hull, M.V., Lustig, K.D., Mangelsdorf, D.J., Shan, B., Identification of a nuclear receptor for bile acids. Science 284 (1999), 1362–1365.
70. Marschall, H.U., Beuers, U., When bile acids don't get amidated. Gastroenterology 144 (2013), 870–873.
71. Marschall, H.U., Roeb, E., Yildiz, Y., Busch, N., Nguyen, H., Purucker, E., Thomas, H.G., Matern, S., Study of human isoursodeoxycholic acid metabolism. J. Hepatol. 26 (1997), 863–870.
72. Marschall, H.U., Oppermann, U.C., Svensson, S., Nordling, E., Persson, B., Höög, J.O., Jörnvall, H., Human liver class I alcohol dehydrogenase gammagamma isozyme: the sole cytosolic 3beta-hydroxysteroid dehydrogenase of iso bile acids. Hepatology 31 (2000), 990–996.
73. Martin, F.P., Dumas, M.E., Wang, Y., Legido-Quigley, C., Yap, I.K., Tang, H., Zirah, S., Murphy, G.M., Cloarec, O., Lindon, J.C., et al. A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model. Mol. Syst. Biol., 3, 2007, 112.
74. Martin, F.P., Wang, Y., Sprenger, N., Yap, I.K., Rezzi, S., Ramadan, Z., Peré-Trepat, E., Rochat, F., Cherbut, C., van Bladeren, P., et al. Top-down systems biology integration of conditional prebiotic modulated transgenomic interactions in a humanized microbiome mouse model. Mol. Syst. Biol., 4, 2008, 205.
75. Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Nakamura, T., Itadani, H., Tanaka, K., Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun. 298 (2002), 714–719.
76. Maruyama, T., Tanaka, K., Suzuki, J., Miyoshi, H., Harada, N., Nakamura, T., Miyamoto, Y., Kanatani, A., Tamai, Y., Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice. J. Endocrinol. 191 (2006), 197–205.
77. McGavigan, A.K., Garibay, D., Henseler, Z.M., Chen, J., Bettaieb, A., Haj, F.G., Ley, R.E., Chouinard, M.L., Cummings, B.P., TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut., 2015, 10.1136/gutjnl-2015-309871 Published online October 28, 2015.
78. Midtvedt, T., Microbial bile acid transformation. Am. J. Clin. Nutr. 27 (1974), 1341–1347.
79. Moschen, A.R., Kaser, S., Tilg, H., Non-alcoholic steatohepatitis: a microbiota-driven disease. Trends Endocrinol. Metab. 24 (2013), 537–545.
80. Mudaliar, S., Henry, R.R., Sanyal, A.J., Morrow, L., Marschall, H.U., Kipnes, M., Adorini, L., Sciacca, C.I., Clopton, P., Castelloe, E., 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 (2013), 574–582.e1.
81. Mueller, M., Thorell, A., Claudel, T., Jha, P., Koefeler, H., Lackner, C., Hoesel, B., Fauler, G., Stojakovic, T., Einarsson, C., et al. Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity. J. Hepatol. 62 (2015), 1398–1404.
82. Neuschwander-Tetri, B.A., Loomba, R., Sanyal, A.J., Lavine, J.E., Van Natta, M.L., Abdelmalek, M.F., Chalasani, N., Dasarathy, S., Diehl, A.M., Hameed, B., et al., NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385 (2015), 956–965.
83. Parks, D.J., Blanchard, S.G., Bledsoe, R.K., Chandra, G., Consler, T.G., Kliewer, S.A., Stimmel, J.B., Willson, T.M., Zavacki, A.M., Moore, D.D., Lehmann, J.M., Bile acids: natural ligands for an orphan nuclear receptor. Science 284 (1999), 1365–1368.
84. Parseus, A., Sommer, N., Sommer, F., Caesar, R., Molinaro, A., Stahlman, M., Greiner, T.U., Perkins, R., Backhed, F., Microbiota-induced obesity requires farnesoid X receptor. Gut., 2016, 10.1136/gutjnl-2015-310283 Published online January 6, 2016.
85. Potthoff, M.J., Kliewer, S.A., Mangelsdorf, D.J., Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev. 26 (2012), 312–324.
86. Prawitt, J., Abdelkarim, M., Stroeve, J.H., Popescu, I., Duez, H., Velagapudi, V.R., Dumont, J., Bouchaert, E., van Dijk, T.H., Lucas, A., et al. Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes 60 (2011), 1861–1871.
87. Ridlon, J.M., Bajaj, J.S., The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics. Acta Pharm. Sin. B 5 (2015), 99–105.
88. Ridlon, J.M., Kang, D.J., Hylemon, P.B., Bile salt biotransformations by human intestinal bacteria. J. Lipid Res. 47 (2006), 241–259.
89. Ridlon, J.M., Kang, D.J., Hylemon, P.B., Bajaj, J.S., Bile acids and the gut microbiome. Curr. Opin. Gastroenterol. 30 (2014), 332–338.
90. Riottot, M., Sacquet, E., Increase in the ileal absorption rate of sodium taurocholate in germ-free or conventional rats given an amylomaize-starch diet. Br. J. Nutr. 53 (1985), 307–310.
91. Russell, D.W., The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem. 72 (2003), 137–174.
92. Ryan, K.K., Tremaroli, V., Clemmensen, C., Kovatcheva-Datchary, P., Myronovych, A., Karns, R., Wilson-Pérez, H.E., Sandoval, D.A., Kohli, R., Bäckhed, F., Seeley, R.J., FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 509 (2014), 183–188.
93. Sacquet, E.C., Gadelle, D.P., Riottot, M.J., Raibaud, P.M., Absence of transformation of beta-muricholic acid by human microflora implanted in the digestive tracts of germfree male rats. Appl. Environ. Microbiol. 47 (1984), 1167–1168.
94. Sacquet, E., Parquet, M., Riottot, M., Raizman, A., Nordlinger, B., Infante, R., Metabolism of beta-muricholic acid in man. Steroids 45 (1985), 411–426.
95. Sayin, S.I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H.U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., Bäckhed, F., Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17 (2013), 225–235.
96. Schaap, F.G., Trauner, M., Jansen, P.L., Bile acid receptors as targets for drug development. Nat. Rev. Gastroenterol. Hepatol. 11 (2014), 55–67.
97. Schmitt, J., Kong, B., Stieger, B., Tschopp, O., Schultze, S.M., Rau, M., Weber, A., Müllhaupt, B., Guo, G.L., Geier, A., Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal. Liver Int. 35 (2015), 1133–1144.
98. Schnabl, B., Brenner, D.A., Interactions between the intestinal microbiome and liver diseases. Gastroenterology 146 (2014), 1513–1524.
99. Selwyn, F.P., Csanaky, I.L., Zhang, Y., Klaassen, C.D., Importance of large intestine in regulating bile acids and glucagon-like peptide-1 in germ-free mice. Drug Metab. Dispos. 43 (2015), 1544–1556.
100. Sinal, C.J., Tohkin, M., Miyata, M., Ward, J.M., Lambert, G., Gonzalez, F.J., Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell 102 (2000), 731–744.
101. Sutherland, J.D., Macdonald, I.A., The metabolism of primary, 7-oxo, and 7 beta-hydroxy bile acids by Clostridium absonum. J. Lipid Res. 23 (1982), 726–732.
102. Teodoro, J.S., Rolo, A.P., Palmeira, C.M., Hepatic FXR: key regulator of whole-body energy metabolism. Trends Endocrinol. Metab. 22 (2011), 458–466.
103. Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., Schoonjans, K., Targeting bile-acid signalling for metabolic diseases. Nat. Rev. Drug Discov. 7 (2008), 678–693.
104. Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 10 (2009), 167–177.
105. Trabelsi, M.S., Daoudi, M., Prawitt, J., Ducastel, S., Touche, V., Sayin, S.I., Perino, A., Brighton, C.A., Sebti, Y., Kluza, J., et al. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat. Commun., 6, 2015, 7629.
106. Tremaroli, V., Karlsson, F., Werling, M., Ståhlman, M., Kovatcheva-Datchary, P., Olbers, T., Fändriks, L., le Roux, C.W., Nielsen, J., Bäckhed, F., Roux-en-Y gastric bypass and vertical banded gastroplasty induce long-term changes on the human gut microbiome contributing to fat mass regulation. Cell Metab. 22 (2015), 228–238.
107. Turnbaugh, P.J., Ridaura, V.K., Faith, J.J., Rey, F.E., Knight, R., Gordon, J.I., The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci. Transl. Med., 1, 2009, 6ra14.
108. Ussar, S., Griffin, N.W., Bezy, O., Fujisaka, S., Vienberg, S., Softic, S., Deng, L., Bry, L., Gordon, J.I., Kahn, C.R., Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome. Cell Metab. 22 (2015), 516–530.
109. Vassileva, G., Golovko, A., Markowitz, L., Abbondanzo, S.J., Zeng, M., Yang, S., Hoos, L., Tetzloff, G., Levitan, D., Murgolo, N.J., et al. Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation. Biochem. J. 398 (2006), 423–430.
110. Vessey, D.A., The biochemical basis for the conjugation of bile acids with either glycine or taurine. Biochem. J. 174 (1978), 621–626.
111. Wang, H., Chen, J., Hollister, K., Sowers, L.C., Forman, B.M., Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol. Cell 3 (1999), 543–553.
112. Wang, Z., Klipfell, E., Bennett, B.J., Koeth, R., Levison, B.S., Dugar, B., Feldstein, A.E., Britt, E.B., Fu, X., Chung, Y.M., et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472 (2011), 57–63.
113. Watanabe, M., Houten, S.M., Mataki, C., Christoffolete, M.A., Kim, B.W., Sato, H., Messaddeq, N., Harney, J.W., Ezaki, O., Kodama, T., et al. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 439 (2006), 484–489.
114. Wostmann, B.S., Intestinal bile acids and cholesterol absorption in the germfree rat. J. Nutr. 103 (1973), 982–990.
115. Wu, G.D., Chen, J., Hoffmann, C., Bittinger, K., Chen, Y.Y., Keilbaugh, S.A., Bewtra, M., Knights, D., Walters, W.A., Knight, R., et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 334 (2011), 105–108.
116. Yang, Z.X., Shen, W., Sun, H., Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease. Hepatol. Int. 4 (2010), 741–748.
117. Yoshimoto, S., Loo, T.M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499 (2013), 97–101.
118. Zhang, Y., Wang, X., Vales, C., Lee, F.Y., Lee, H., Lusis, A.J., Edwards, P.A., FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice. Arterioscler. Thromb. Vasc. Biol. 26 (2006), 2316–2321.
119. Zhang, Y., Ge, X., Heemstra, L.A., Chen, W.D., Xu, J., Smith, J.L., Ma, H., Kasim, N., Edwards, P.A., Novak, C.M., Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice. Mol. Endocrinol. 26 (2012), 272–280.
120. Zhu, Y., Li, F., Guo, G.L., Tissue-specific function of farnesoid X receptor in liver and intestine. Pharmacol. Res. 63 (2011), 259–265.