Full Text:   <3912>

Summary:  <1984>

CLC number: S82

On-line Access: 2015-06-08

Received: 2014-12-02

Revision Accepted: 2015-03-26

Crosschecked: 2015-05-13

Cited: 15

Clicked: 10099

Citations:  Bibtex RefMan EndNote GB/T7714


Xiang-hua Yan


Yang-fan Nie


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.6 P.436-446


Cross-talk between bile acids and intestinal microbiota in host metabolism and health

Author(s):  Yang-fan Nie, Jun Hu, Xiang-hua Yan

Affiliation(s):  College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan 430070, China; more

Corresponding email(s):   xhyan@mail.hzau.edu.cn

Key Words:  Bile acid (BA), Farnesoid X receptor (FXR), Intestinal microbiota, Host metabolism, Autophagy

Yang-fan Nie, Jun Hu, Xiang-hua Yan. Cross-talk between bile acids and intestinal microbiota in host metabolism and health[J]. Journal of Zhejiang University Science B, 2015, 16(6): 436-446.

@article{title="Cross-talk between bile acids and intestinal microbiota in host metabolism and health",
author="Yang-fan Nie, Jun Hu, Xiang-hua Yan",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Cross-talk between bile acids and intestinal microbiota in host metabolism and health
%A Yang-fan Nie
%A Jun Hu
%A Xiang-hua Yan
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 6
%P 436-446
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400327

T1 - Cross-talk between bile acids and intestinal microbiota in host metabolism and health
A1 - Yang-fan Nie
A1 - Jun Hu
A1 - Xiang-hua Yan
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 6
SP - 436
EP - 446
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400327

bile acid (BA) is de novo synthesized exclusively in the liver and has direct or indirect antimicrobial effects. On the other hand, the composition and size of the BA pool can be altered by intestinal microbiota via the biotransformation of primary BAs to secondary BAs, and subsequently regulate the nuclear farnesoid X receptor (FXR; NR1H4). The BA-activated FXR plays important roles in BA synthesis and metabolism, glucose and lipid metabolism, and even hepatic autophagy. BAs can also play a role in the interplays among intestinal microbes. In this review, we mainly discuss the interactions between BAs and intestinal microbiota and their roles in regulating host metabolism, and probably the autophagic signaling pathway.



Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Allaoui, A., Mounier, J., Prevost, M.C., et al., 1992. icsB: a Shigella flexneri virulence gene necessary for the lysis of protrusions during intercellular spread. Mol. Microbiol., 6(12):1605-1616.

[2]Ananthanarayanan, M., Balasubramanian, N., Makishima, M., et al., 2001. Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. J. Biol. Chem., 276(31):28857-28865.

[3]Baxt, L.A., Garza-Mayers, A.C., Goldberg, M.B., 2013. Bacterial subversion of host innate immune pathways. Science, 340(6133):697-701.

[4]Begley, M., Gahan, C.G., Hill, C., 2005. The interaction between bacteria and bile. FEMS Microbiol. Rev., 29(4):625-651.

[5]Bernstein, H., Payne, C.M., Bernstein, C., et al., 1999. Activation of the promoters of genes associated with DNA damage, oxidative stress, ER stress and protein malfolding by the bile salt, deoxycholate. Toxicol. Lett., 108(1):37-46.

[6]Bjorkhem, I., 1992. Mechanism of degradation of the steroid side chain in the formation of bile acids. J. Lipid. Res., 33(4):455-471.

[7]Borody, T.J., Khoruts, A., 2012. Fecal microbiota transplantation and emerging applications. Nat. Rev. Gastroenterol. Hepatol., 9(2):88-96.

[8]Brumell, J.H., Steele-Mortimer, O., Finlay, B.B., 1999. Bacterial invasion: force feeding by salmonella. Curr. Biol., 9(8):R277-R280.

[9]Buffie, C.G., Bucci, V., Stein, R.R., et al., 2015. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature, 517(7533):205-208.

[10]Chiang, J.Y., 2004. Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms. J. Hepatol., 40(3):539-551.

[11]Cremers, C.M., Knoefler, D., Vitvitsky, V., et al., 2014. Bile salts act as effective protein-unfolding agents and instigators of disulfide stress in vivo. PNAS, 111(16):E1610-E1619.

[12]D'Aldebert, E., Biyeyeme Bi Mve, M.J., Mergey, M., et al., 2009. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology, 136(4):1435-1443.

[13]David, L.A., Maurice, C.F., Carmody, R.N., et al., 2014. Diet rapidly and reproducibly alters the human gut microbiome. Nature, 505(7484):559-563.

[14]Dawson, P.A., Hubbert, M., Haywood, J., et al., 2005. The heteromeric organic solute transporter α-β, Ostα-Ostβ, is an ileal basolateral bile acid transporter. J. Biol. Chem., 280(8):6960-6968.

[15]de Aguiar Vallim, T.Q., Tarling, E.J., Edwards, P.A., 2013. Pleiotropic roles of bile acids in metabolism. Cell Metab., 17(5):657-669.

[16]Degirolamo, C., Rainaldi, S., Bovenga, F., et al., 2014. Microbiota modification with probiotics induces hepatic bile acid synthesis via downregulation of the Fxr-Fgf15 axis in mice. Cell Rep., 7(1):12-18.

[17]Denson, L.A., Sturm, E., Echevarria, W., et al., 2001. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp. Gastroenterology, 121(1):140-147.

[18]Deretic, V., Levine, B., 2009. Autophagy, immunity, and microbial adaptations. Cell Host Microbe, 5(6):527-549.

[19]de Valdez, G.F., Martos, G., Taranto, M.P., et al., 1997. Influence of bile on β-galactosidase activity and cell viability of Lactobacillus reuteri when subjected to freeze-drying. J. Dairy Sci., 80(9):1955-1958.

[20]Devkota, S., Wang, Y., Musch, M.W., et al., 2012. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice. Nature, 487(7405):104-108.

[21]Ding, J.W., Andersson, R., Soltesz, V., et al., 1993. The role of bile and bile acids in bacterial translocation in obstructive jaundice in rats. Eur. Surg. Res., 25(1):11-19.

[22]Doerner, K.C., Takamine, F., Lavoie, C.P., et al., 1997. Assessment of fecal bacteria with bile acid 7α-dehydroxylating activity for the presence of bai-like genes. Appl. Environ. Microbiol., 63(3):1185-1188.

[23]Dortet, L., Mostowy, S., Samba-Louaka, A., et al., 2011. Recruitment of the major vault protein by InlK: a Listeria monocytogenes strategy to avoid autophagy. PLoS Pathog., 7(8):e1002168.

[24]Eloranta, J.J., Kullak-Ublick, G.A., 2008. The role of FXR in disorders of bile acid homeostasis. Physiology, 23(5):286-295.

[25]Francis, M.B., Allen, C.A., Shrestha, R., et al., 2013. Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection. PLoS Pathog., 9(5):e1003356.

[26]Frankenberg, T., Rao, A., Chen, F., et al., 2006. Regulation of the mouse organic solute transporter α-β, Ostα-Ostβ, by bile acids. Am. J. Physiol. Gastrointest. Liver Physiol., 290(5):G912-G922.

[27]Giel, J.L., Sorg, J.A., Sonenshein, A.L., et al., 2010. Metabolism of bile salts in mice influences spore germination in Clostridium difficile. PLoS ONE, 5(1):e8740.

[28]Goodwin, B., Jones, S.A., Price, R.R., et al., 2000. A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol. Cell, 6(3):517-526.

[29]Hardison, W.G., 1978. Hepatic taurine concentration and dietary taurine as regulators of bile acid conjugation with taurine. Gastroenterology, 75(1):71-75.

[30]Hayakawa, S., 1982. Microbial transformation of bile acids. A unified scheme for bile acid degradation, and hydroxylation of bile acids. Z. Allg. Mikrobiol., 22(5):309-326.

[31]Heeg, D., Burns, D.A., Cartman, S.T., et al., 2012. Spores of Clostridium difficile clinical isolates display a diverse germination response to bile salts. PLoS ONE, 7(2):e32381.

[32]Heuman, D.M., Bajaj, R.S., Lin, Q., 1996. Adsorption of mixtures of bile salt taurine conjugates to lecithin-cholesterol membranes: implications for bile salt toxicity and cytoprotection. J. Lipid Res., 37(3):562-573.

[33]Hill, D.A., Artis, D., 2010. Intestinal bacteria and the regulation of immune cell homeostasis. Annu. Rev. Immunol., 28:623-667.

[34]Holt, J.A., Luo, G., Billin, A.N., et al., 2003. Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev., 17(13):1581-1591.

[35]Houten, S.M., Watanabe, M., Auwerx, J., 2006. Endocrine functions of bile acids. EMBO J., 25(7):1419-1425.

[36]Hu, X., Bonde, Y., Eggertsen, G., et al., 2014. Muricholic bile acids are potent regulators of bile acid synthesis via a positive feedback mechanism. J. Intern. Med., 275(1):27-38.

[37]Hwang, S.T., Urizar, N.L., Moore, D.D., et al., 2002. Bile acids regulate the ontogenic expression of ileal bile acid binding protein in the rat via the farnesoid X receptor. Gastroenterology, 122(5):1483-1492.

[38]Inagaki, T., Moschetta, A., Lee, Y.K., et al., 2006. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. PNAS, 103(10):3920-3925.

[39]Islam, K.B., Fukiya, S., Hagio, M., et al., 2011. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology, 141(5):1773-1781.

[40]Joubert, P.E., Meiffren, G., Gregoire, I.P., et al., 2009. Autophagy induction by the pathogen receptor CD46. Cell Host Microbe, 6(4):354-366.

[41]Joyce, S.A., Macsharry, J., Casey, P.G., et al., 2014. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. PNAS, 111(20):7421-7426.

[42]Kandell, R.L., Bernstein, C., 1991. Bile salt/acid induction of DNA damage in bacterial and mammalian cells: implications for colon cancer. Nutr. Cancer, 16(3-4):227-238.

[43]Kau, A.L., Ahern, P.P., Griffin, N.W., et al., 2011. Human nutrition, the gut microbiome and the immune system. Nature, 474(7351):327-336.

[44]Kim, I., Ahn, S.H., Inagaki, T., et al., 2007. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J. Lipid Res., 48(12):2664-2672.

[45]Kurdi, P., Kawanishi, K., Mizutani, K., et al., 2006. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria. J. Bacteriol., 188(5):1979-1986.

[46]Laue, H., Denger, K., Cook, A.M., 1997. Taurine reduction in anaerobic respiration of Bilophila wadsworthia RZATAU. Appl. Environ. Microbiol., 63(5):2016-2021.

[47]Lee, J.M., Wagner, M., Xiao, R., et al., 2014. Nutrient-sensing nuclear receptors coordinate autophagy. Nature, 516(7529):112-115.

[48]Lefebvre, P., Cariou, B., Lien, F., et al., 2009. Role of bile acids and bile acid receptors in metabolic regulation. Physiol. Rev., 89(1):147-191.

[49]Levine, B., Mizushima, N., Virgin, H.W., 2011. Autophagy in immunity and inflammation. Nature, 469(7330):323-335.

[50]Li, F., Jiang, C., Krausz, K.W., et al., 2013. Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity. Nat. Commun., 4:2384.

[51]Li, H., Chen, F., Shang, Q., et al., 2005. FXR-activating ligands inhibit rabbit ASBT expression via FXR-SHP-FTF cascade. Am. J. Physiol. Gastrointest. Liver Physiol., 288(1):G60-G66.

[52]Li, T., Chiang, J.Y.L., 2013. Nuclear receptors in bile acid metabolism. Drug Metab. Rev., 45(1):145-155.

[53]Lorenzo-Zúñiga, V., Bartoli, R., Planas, R., et al., 2003. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology, 37(3):551-557.

[54]Makishima, M., Okamoto, A.Y., Repa, J.J., et al., 1999. Identification of a nuclear receptor for bile acids. Science, 284(5418):1362-1365.

[55]Mcgarr, S.E., Ridlon, J.M., Hylemon, P.B., 2005. Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J. Clin. Gastroenterol., 39(2):98-109.

[56]Midtvedt, T., 1974. Microbial bile acid transformation. Am. J. Clin. Nutr., 27(11):1341-1347.

[57]Miyata, M., Takamatsu, Y., Kuribayashi, H., et al., 2009. Administration of ampicillin elevates hepatic primary bile acid synthesis through suppression of ileal fibroblast growth factor 15 expression. J. Pharmacol. Exp. Ther., 331(3):1079-1085.

[58]Miyata, M., Yamakawa, H., Hamatsu, M., et al., 2011. Enterobacteria modulate intestinal bile acid transport and homeostasis through apical sodium-dependent bile acid transporter (SLC10A2) expression. J. Pharmacol. Exp. Ther., 336(1):188-196.

[59]Murphy, E.F., Cotter, P.D., Healy, S., et al., 2010. Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models. Gut, 59(12):1635-1642.

[60]Myant, N.B., Mitropoulos, K.A., 1977. Cholesterol 7α-hydroxylase. J. Lipid Res., 18(2):135-153.

[61]Nguyen, A., Bouscarel, B., 2008. Bile acids and signal transduction: role in glucose homeostasis. Cell. Signal., 20(12):2180-2197.

[62]Noh, D.O., Gilliland, S.E., 1993. Influence of bile on cellular integrity and β-galactosidase activity of Lactobacillus acidophilus. J. Dairy Sci., 76(5):1253-1259.

[63]Ridlon, J.M., Kang, D.J., Hylemon, P.B., 2006. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res., 47(2):241-259.

[64]Ridlon, J.M., Kang, D.J., Hylemon, P.B., et al., 2014. Bile acids and the gut microbiome. Curr. Opin. Gastroenterol., 30(3):332-338.

[65]Rupnik, M., Wilcox, M.H., Gerding, D.N., 2009. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol., 7(7):526-536.

[66]Russell, D.W., 2003. The enzymes, regulation, and genetics of bile acid synthesis. Annu. Rev. Biochem., 72:137-174.

[67]Sayin, S.I., Wahlstrom, A., Felin, J., et al., 2013. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab., 17(2):225-235.

[68]Schnaith, A., Kashkar, H., Leggio, S.A., et al., 2007. Staphylococcus aureus subvert autophagy for induction of caspase-independent host cell death. J. Biol. Chem., 282(4):2695-2706.

[69]Sekirov, I., Finlay, B.B., 2009. The role of the intestinal microbiota in enteric infection. J. Physiol., 587(17):4159-4167.

[70]Seok, S., Fu, T., Choi, S.E., et al., 2014. Transcriptional regulation of autophagy by an FXR-CREB axis. Nature, 516(7529):108-111.

[71]Sinha, J., Chen, F., Miloh, T., et al., 2008. β-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes. Am. J. Physiol. Gastrointest. Liver Physiol., 295(5):G996-G1003.

[72]Sorg, J.A., Sonenshein, A.L., 2008. Bile salts and glycine as cogerminants for Clostridium difficile spores. J. Bacteriol., 190(7):2505-2512.

[73]Sorg, J.A., Sonenshein, A.L., 2010. Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid. J. Bacteriol., 192(19):4983-4990.

[74]Starr, T., Child, R., Wehrly, T.D., et al., 2012. Selective subversion of autophagy complexes facilitates completion of the Brucella intracellular cycle. Cell Host Microbe, 11(1):33-45.

[75]Swann, J.R., Want, E.J., Geier, F.M., et al., 2011. Systemic gut microbial modulation of bile acid metabolism in host tissue compartments. PNAS, 108(Suppl. 1):4523-4530.

[76]Tremaroli, V., Backhed, F., 2012. Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415):242-249.

[77]Vrieze, A., Out, C., Fuentes, S., et al., 2014. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. J. Hepatol., 60(4):824-831.

[78]Wang, D.Q., Cohen, D.E., Carey, M.C., 2009. Biliary lipids and cholesterol gallstone disease. J. Lipid Res., 50(Suppl.):S406-S411.

[79]Weingarden, A.R., Chen, C., Bobr, A., et al., 2014. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol., 306(4):G310-G319.

[80]Wostmann, B.S., 1973. Intestinal bile acids and cholesterol absorption in the germfree rat. J. Nutr., 103(7):982-990.

[81]Yoshimoto, S., Loo, T.M., Atarashi, K., et al., 2013. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature, 499(7456):97-101.

[82]Zhang, Y., Limaye, P.B., Renaud, H.J., et al., 2014. Effect of various antibiotics on modulation of intestinal microbiota and bile acid profile in mice. Toxicol. Appl. Pharmacol., 277(2):138-145.

[83]Zollner, G., Marschall, H.U., Wagner, M., et al., 2006. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations. Mol. Pharm., 3(3):231-251.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE