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Bile acids in regulation of intestinal physiology

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Abstract

In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

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References and Recommended Reading

  1. Hofmann AF: The enterohepatic circulation of bile acids in mammals: form and functions. Front Biosci 2009, 14:2584–2598.

    Article  PubMed  CAS  Google Scholar 

  2. Alrefai W, Gill R: Bile acid transporters: Structure, function, regulation and pathophysiological implications. Pharm Res 2007, 24:1803–1823.

    Article  PubMed  CAS  Google Scholar 

  3. Rao A, Haywood J, Craddock A, et al.: The organic solute transporter alpha-beta, Ost α-Ostβ, is essential for intestinal bile acid transport and homeostasis. Proc Natl Acad Sci 2008, 105:3891–3896.

    Article  PubMed  CAS  Google Scholar 

  4. Schmidt D, Mangelsdorf D: Nuclear receptors of the enteric tract: guarding the frontier. Nutr Rev 2008, 66:S88–S97.

    Article  PubMed  Google Scholar 

  5. Scotti E, Gilardi F, Godio C, et al.: Bile acids and their signaling pathways: eclectic regulators of diverse cellular functions. Cell Mol Life Sci 2007, 64:2477–2491.

    Article  PubMed  CAS  Google Scholar 

  6. Inagaki T, Moschetta A, Lee Y, et al.: Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Proc Natl Acad Sci 2006, 103:3920–3925.

    Article  PubMed  CAS  Google Scholar 

  7. Maran RRM, Thomas A, Roth M, et al.: Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development. J Pharmacol Exp Ther 2009, 328:469–477.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Thomas C, Auwerx J, Schoonjans K: Bile acids and the membrane bile acid receptor TGR5: Connecting nutrition and metabolism. Thyroid 2008, 18:167–174.

    Article  PubMed  CAS  Google Scholar 

  10. Watanabe M, Houten SM, Mataki C, et al.: Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006, 439:484–489.

    Article  PubMed  CAS  Google Scholar 

  11. Yasuda H, Hirata S, Inoue K, et al.: Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochem Biophys Res Commun 2007, 354:154–159.

    Article  PubMed  CAS  Google Scholar 

  12. Merchant NB, Rogers CM, Trivedi B, et al.: Ligand-dependent activation of the epidermal growth factor receptor by secondary bile acids in polarizing colon cancer cells. Surgery 2005, 138:415–421.

    Article  PubMed  Google Scholar 

  13. Cheng K, Raufman J: Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors. Biochem Pharmacol 2005, 70:1035–1047.

    Article  PubMed  CAS  Google Scholar 

  14. Jean-Louis S, Akare S, Ali M, et al.: Deoxycholic acid induces intracellular signaling through membrane perturbations. J Biol Chem 2006, 281:14948–14960.

    Article  PubMed  CAS  Google Scholar 

  15. Akare S, Martinez J: Bile acid induces hydrophobicitydependent membrane alterations. Biochim Biophys Acta 2005, 1735:59–67.

    PubMed  CAS  Google Scholar 

  16. Yui S, Kanamoto R, Saeki T: Biphasic regulation of cell death and survival by hydrophobic bile acids in HCT116 cells. Nutr Cancer 2009, 61:374–380.

    Article  PubMed  CAS  Google Scholar 

  17. Katona B, Anant S, Covey D, et al.: Characterization of enantiomeric bile acid-induced apoptosis in colon cancer cell lines. J Biol Chem 2009, 284:3354–3364.

    Article  PubMed  CAS  Google Scholar 

  18. Shah SA, Looby E, Volkov Y, et al.: Ursodeoxycholic acid inhibits translocation of protein kinase C in human colonic cancer cell lines. Eur J Cancer 2005, 41:2160–2169.

    Article  PubMed  CAS  Google Scholar 

  19. Solá S, Aranha M, Steer C, et al.: Game and players: mitochondrial apoptosis and the therapeutic potential of ursodeoxycholic acid. Curr Issues Mol Biol 2007, 9:123–138.

    PubMed  Google Scholar 

  20. Wachs F-P, Krieg RC, Rodrigues CMP, et al.: Bile salt-induced apoptosis in human colon cancer cell lines involves the mitochondrial transmembrane potential but not the CD95 (Fas/Apo-1) receptor. Int J Colorectal Dis 2005, 20:103–113.

    Article  PubMed  Google Scholar 

  21. Payne CM, Weber C, Crowley-Skillicorn C, et al.: Deoxycholate induces mitochondrial oxidative stress and activates NF-{kappa}B through multiple mechanisms in HCT-116 colon epithelial cells. Carcinogenesis 2007, 28:215–222.

    Article  PubMed  CAS  Google Scholar 

  22. Shant J, Cheng K, Marasa BS, et al.: Akt-dependent NF-[kappa]B activation is required for bile acids to rescue colon cancer cells from stress-induced apoptosis. Exp Cell Res 2009, 315:432–450.

    Article  PubMed  CAS  Google Scholar 

  23. Toledo A, Yamaguchi J, Wang J-Y, et al.: Taurodeoxycholate stimulates intestinal cell proliferation and protects against apoptotic cell death through activation of NF-{kappa}B. Dig Dis Sci 2004, 49:1664–1671.

    Article  PubMed  CAS  Google Scholar 

  24. Raimondi F, Santoro P, Barone MV, et al.: Bile acids modulate tight junction structure and barrier function of Caco-2 monolayers via EGFR activation. Am J Physiol Gastrointest Liver Physiol 2008, 294:G906–G913.

    Article  PubMed  CAS  Google Scholar 

  25. Freel RW, Hatch M, Earnest DL, et al.: Role of tight-junctional pathways in bile salt-induced increases in colonic permeability. Am J Physiol Gastrointest Liver Physiol 1983, 245:G816–G823.

    CAS  Google Scholar 

  26. Henrikson C, Argenzio R, Liacos J, et al.: Morphologic and functional effects of bile salt on the porcine colon during injury and repair. Lab Invest 1989, 60:72–87.

    PubMed  CAS  Google Scholar 

  27. Münch A, Strom M, Soderholm J: Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies. Scand J Gastroenterol 2007, 42:1167–1174.

    Article  PubMed  CAS  Google Scholar 

  28. Tsutsumi K, Li S, Hymas R, et al.: Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer. J Pharm Sci 2008, 97:350–367.

    Article  PubMed  CAS  Google Scholar 

  29. Barcelo A, Claustre J, Toumi F, et al.: Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon. Dig Dis Sci 2001, 46:1223–1231.

    Article  PubMed  CAS  Google Scholar 

  30. Strauch ED, Yamaguchi J, Bass BL, et al.: Bile salts regulate intestinal epithelial cell migration by nuclear factor-[kappa]B-induced expression of transforming growth factor-[beta]. J Am Coll Surg 2003, 197:974–984.

    Article  PubMed  Google Scholar 

  31. Mühlbauer M, Allard B, Bosserhoff AK, et al.: Differential effects of deoxycholic acid and taurodeoxycholic acid on NF-{kappa}B signal transduction and IL-8 gene expression in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2004, 286:G1000–G1008.

    Article  PubMed  Google Scholar 

  32. Barrett K, Keely S: Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. Ann Rev Physiol 2000, 62:535–572.

    Article  CAS  Google Scholar 

  33. Smith MJ, Cherian P, Raju GS, et al.: Bile acid malabsorption in persistent diarrhoea. J R Coll Physicians Lond 2000, 34:448–451.

    PubMed  CAS  Google Scholar 

  34. Fan X, Sellin JH: Small intestinal bacterial overgrowth, bile acid malabsorption and gluten intolerance as possible causes of chronic watery diarrhea. Aliment Pharmacol Ther 2009, 29:1069–1077.

    Article  PubMed  CAS  Google Scholar 

  35. Balesaria S, Pell RJ, Abbott LJ, et al.: Exploring possible mechanisms for primary bile acid malabsorption: evidence for different regulation of ileal bile acid transporter transcripts in chronic diarrhoea. Eur J Gastroenterol Hepatol 2008, 20:413–422.

    Article  PubMed  CAS  Google Scholar 

  36. Walters JR, Tasleem AM, Omer OS, et al.: A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol 2009 (Epub ahead of print).

  37. Mekjian HS, Phillips SF, Hofmann AF: Colonic secretion of water and electrolytes induced by bile acids: perfusion studies in man. J Clin Invest 1971, 50:1569–1577.

    Article  PubMed  CAS  Google Scholar 

  38. Chadwick VS, Gaginella TS, Carlson GL, et al.: Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon. J Lab Clin Med 1979, 94:661–674.

    PubMed  CAS  Google Scholar 

  39. Dharmsathaphorn K, Huott PA, Vongkovit P, et al.: Cl-secretion induced by bile salts. A study of the mechanism of action based on a cultured colonic epithelial cell line. J Clin Invest 1989, 84:945–953.

    Article  PubMed  CAS  Google Scholar 

  40. Gelbmann CM, Schteingart CD, Thompson SM, et al.: Mast cells and histamine contribute to bile acid-stimulated secretion in the mouse colon. J Clin Invest 1995, 95:2831–2839.

    Article  PubMed  CAS  Google Scholar 

  41. Mauricio AC, Slawik M, Heitzmann D, et al.: Deoxycholic acid (DOC) affects the transport properties of distal colon. Pflügers Arch 2000, 439:532–540.

    Article  PubMed  CAS  Google Scholar 

  42. Kanchanapoo J, Ao M, Prasad R et al.: Role of protein kinase C-delta in the age-dependent secretagogue action of bile acids in mammalian colon. Am J Physiol Cell Physiol 2007, 293:C1851–C1861.

    Article  PubMed  CAS  Google Scholar 

  43. Keely S, Scharl M, Bertelsen L, et al.: Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships. Am J Physiol Gastrointest Liver Physiol 2007, 292:G290–G297.

    Article  PubMed  CAS  Google Scholar 

  44. Sciarretta G, Furno A, Morrone B, et al.: Absence of histopathological changes of ileum and colon in functional chronic diarrhea associated with bile acid malabsorption, assessed by SeHCAT test: a prospective study. Am J Gastroenterol 1994, 89:1058–1061.

    PubMed  CAS  Google Scholar 

  45. Kidd M, Modlin IM, Gustafsson BI, et al.: Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 2008, 295:G260–G272.

    Article  PubMed  CAS  Google Scholar 

  46. Karlstrom L: Evidence of involvement of the enteric nervous system in the effects of sodium deoxycholate on small-intestinal transepithelial fluid transport and motility. Scand J Gastroenterol 1986, 21:321–330.

    Article  PubMed  CAS  Google Scholar 

  47. Matsumura M, Saito S: Effect of bile salts on the plasma concentration of immunoreactive vasoactive intestinal polypeptide in man. Endocrinol Jpn 1989, 36:15–21.

    PubMed  CAS  Google Scholar 

  48. Miyata R, Iwabuchi K, Watanabe S, et al.: Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion. Inflamm Res 1999, 48:265–273.

    Article  PubMed  CAS  Google Scholar 

  49. Correia L, Podevin P, Borderie D, et al.: Effects of bile acids on the humoral immune response: a mechanistic approach. Life Sci 2001, 69:2337–2348.

    Article  PubMed  CAS  Google Scholar 

  50. Souza RF, Krishnan K, Spechler SJ: Acid, bile, and CDX: the ABCs of making Barrett’s metaplasia. Am J Physiol Gastrointest Liver Physiol 2008, 295:G211–G218.

    Article  PubMed  CAS  Google Scholar 

  51. Pardi DS, Loftus EV, Kremers WK, et al.: Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis. Gastroenterology 2003, 124:889–893.

    Article  PubMed  CAS  Google Scholar 

  52. Kullmann F, Arndt H, Gross V, et al.: Beneficial effect of ursodeoxycholic acid on mucosal damage in trinitrobenzene sulphonic acid-induced colitis. Eur J Gastroenterol Hepatol 1997, 9:1205–1211.

    PubMed  CAS  Google Scholar 

  53. Lepercq P, Hermier D, David O, et al.: Increasing ursodeoxycholic acid in the enterohepatic circulation of pigs through the administration of living bacteria. Brit J Nutr 2005, 93:457–469.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Stephen J. Keely.

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Keating, N., Keely, S.J. Bile acids in regulation of intestinal physiology. Curr Gastroenterol Rep 11, 375–382 (2009). https://doi.org/10.1007/s11894-009-0057-8

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