Roles of Bile Acid as an Active Biological Substance

담즙산의 생체 활성 물질로서의 역할

  • Received : 2011.03.08
  • Accepted : 2011.06.15
  • Published : 2011.06.30

Abstract

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

Keywords

References

  1. Attili AF, Angelico M, Cantafora A, et al., Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids. Med Hypotheses. 1986; 19(1): 57-69. https://doi.org/10.1016/0306-9877(86)90137-4
  2. Paumgartner G, Beuers U: Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology 2002; 36(3): 525-31. https://doi.org/10.1053/jhep.2002.36088
  3. Thomas C, Pellicciari R, Pruzanski M, et al., Targeting bileacid signalling for metabolic diseases. Nat Rev Drug Discov 2008; 7(8): 678-93. https://doi.org/10.1038/nrd2619
  4. Huang L, Sun Y, Zhu H, et al., Synthesis and antimicrobial evaluation of bile acid tridentate conjugates. Steroids. 2009; 74(8): 701-6. https://doi.org/10.1016/j.steroids.2009.03.005
  5. Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004; 126(1): 322-42. https://doi.org/10.1053/j.gastro.2003.06.005
  6. Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004; 126(1): 322-42. https://doi.org/10.1053/j.gastro.2003.06.005
  7. Krishnamurthy GT, Brown PH. Comparison of fatty meal and intravenous cholecystokinin infusion for gallbladder ejection fraction. J Nucl Med 2002; 43(12): 1603-10.
  8. Javitt NB. Cholesterol, hydroxycholesterols, and bile acids. Biochem Biophys Res Commun. 2002; 292(5): 1147-53. https://doi.org/10.1006/bbrc.2001.2013
  9. Redinger RN. The coming of age of our understanding of the enterohepatic circulation of bile salts. Am J Surg 2003; 185(2): 168-72. https://doi.org/10.1016/S0002-9610(02)01212-6
  10. Hofmann AF. The continuing importance of bile acids in liver and intestinal disease. Arch Intern Med 1999; 159(22): 2647-58. https://doi.org/10.1001/archinte.159.22.2647
  11. Ayaki Y, Tsuma-Date T, Endo S, et al., Role of endogenous and exogenous cholesterol in liver as the precursor for bile acids in rats. Steroids 1981; 38(5): 495-509. https://doi.org/10.1016/0039-128X(81)90050-7
  12. Gustafsson BE, Angelin B, Einarsson K, et al., Effects of cholesterol feeding on synthesis and metabolism of cholesterol and bile acids in germfree rats. J Lipid Res 1977; 18(6): 717-21.
  13. Martinez-Augustin O, Sanchez de Medina F. Intestinal bile acid physiology and pathophysiology. World J Gastroenterol 2008; 14(37): 5630-40. https://doi.org/10.3748/wjg.14.5630
  14. Shneider BL. Intestinal bile acid transport: biology, physiology, and pathophysiology. J Pediatr Gastroenterol Nutr 2001; 32(4): 407-17. https://doi.org/10.1097/00005176-200104000-00002
  15. Craddock AL, Love MW, Daniel RW, et al., Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol 1998; 274(1 Pt 1): G157-69.
  16. Trauner M, Boyer JL. Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev 2003; 83(2): 633-71. https://doi.org/10.1152/physrev.00027.2002
  17. Hylemon PBHarder J. Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems. FEMS Microbiol Rev 1998; 22(5): 475-88. https://doi.org/10.1111/j.1574-6976.1998.tb00382.x
  18. Playoust MR, Isselbacher KJ. Studies on the Transport and Metabolism of Conjugated Bile Salts by Intestinal Mucosa. J Clin Invest 1964; 43(4): 67-76.
  19. Hardison W, GRosenberg IH. Bile-salt deficiency in the steatorrhea following resection of the ileum and proximal colon. N Engl J Med 1967; 277(7): 337-42. https://doi.org/10.1056/NEJM196708172770704
  20. Hofmann AF, Poley JR. Cholestyramine treatment of diarrhea associated with ileal resection. N Engl J Med 1969; 281(8): 397-402. https://doi.org/10.1056/NEJM196908212810801
  21. Danielsson A, Nyhlin H, Persson H, et al., Chronic diarrhoea after radiotherapy for gynaecological cancer: occurrence and aetiology. Gut 1991; 32(10): 1180-7. https://doi.org/10.1136/gut.32.10.1180
  22. Rutgeerts P, Ghoos Y, Vantrappen G. Kinetics of primary bile acids in patients with non-operated Crohn's disease. Eur J Clin Invest 1982; 12(2): 135-43. https://doi.org/10.1111/j.1365-2362.1982.tb00950.x
  23. Fernandez-Banares F, Esteve M, Salas A, et al., Systematic evaluation of the causes of chronic watery diarrhea with functional characteristics. Am J Gastroenterol 2007; 102(11): 2520-8. https://doi.org/10.1111/j.1572-0241.2007.01438.x
  24. Wedlake L, A'Hern R, Russell D, et al., Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoeapredominant irritable bowel syndrome. Aliment Pharmacol Ther 2009; 30(7): 707-17. https://doi.org/10.1111/j.1365-2036.2009.04081.x
  25. Suhr O, Danielsson A, Nyhlin H, et al., Bile acid malabsorption demonstrated by SeHCAT in chronic diarrhoea, with special reference to the impact of cholecystectomy. Scand J Gastroenterol 1988; 23(10): 1187-94. https://doi.org/10.3109/00365528809090189
  26. Walters MP, Littlewood JM. Faecal bile acid and dietary residue excretion in cystic fibrosis: age group variations. J Pediatr Gastroenterol Nutr 1998; 27(3): 296-300. https://doi.org/10.1097/00005176-199809000-00005
  27. Ronnblom A, Andersson S, Danielsson A. Mechanisms of diarrhoea in myotonic dystrophy. Eur J Gastroenterol Hepatol 1998; 10(7): 607-10. https://doi.org/10.1097/00042737-199807000-00015
  28. van Faassen A, Hazen MJ, van den Brandt PA, et al., Bile acids and pH values in total feces and in fecal water from habitually omnivorous and vegetarian subjects. Am J Clin Nutr 1993; 58(6): 917-22. https://doi.org/10.1093/ajcn/58.6.917
  29. de Kok TM, van Faassen A, Glinghammar B, et al., Bile acid concentrations, cytotoxicity, and pH of fecal water from patients with colorectal adenomas. Dig Dis Sci 1999; 44(11): 2218-25. https://doi.org/10.1023/A:1026644418142
  30. Stadler J, Yeung KS, Furrer R, et al., Proliferative activity of rectal mucosa and soluble fecal bile acids in patients with normal colons and in patients with colonic polyps or cancer. Cancer Lett 1988; 38(3): 315-20. https://doi.org/10.1016/0304-3835(88)90023-7
  31. Norman A. Faecal Excretion Products of Cholic Acid in Man. Br J Nutr 1964; 18(1): 73-86.
  32. Hofmann AF. Bile acids, diarrhea, and antibiotics: data, speculation, and a unifying hypothesis. J Infect Dis 1977; 135(S1): 26-32.
  33. Eastwood MA, Hamilton D. Studies on the adsorption of bile salts to non-absorbed components of diet. Biochim Biophys Acta 1968; 152(1): 165-73. https://doi.org/10.1016/0005-2760(68)90018-0
  34. Duane WC. The intermicellar bile salt concentration in equilibrium with the mixed-micelles of human bile. Biochim Biophys Acta 1975; 398(2): 275-86. https://doi.org/10.1016/0005-2760(75)90143-5
  35. Thomas LA, Veysey MJ, French G, et al., Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples. Gut 2001; 49(6): 835-42. https://doi.org/10.1136/gut.49.6.835
  36. Bernstein H, Bernstein C, Payne CM, et al: Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 2005; 589(1): 47-65. https://doi.org/10.1016/j.mrrev.2004.08.001
  37. Morvay K, Szentleleki K, Torok G, et al., Effect of change of fecal bile acid excretion achieved by operative procedures on 1,2-dimethylhydrazine-induced colon cancer in rats. Dis Colon Rectum 1989; 32(10): 860-3. https://doi.org/10.1007/BF02554556
  38. Ochsenkuhn T, Bayerdorffer E, Meining A, et al., Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer 1999; 85(8): 1664-9. https://doi.org/10.1002/(SICI)1097-0142(19990415)85:8<1664::AID-CNCR4>3.0.CO;2-O
  39. Kasbo J, Saleem M, Perwaiz S, et al., Biliary, fecal and plasma deoxycholic acid in rabbit, hamster, guinea pig, and rat: comparative study and implication in colon cancer. Biol Pharm Bull 2002; 25(10): 1381-4. https://doi.org/10.1248/bpb.25.1381
  40. van Faassen A, Ochsenkuhn T, Houterman S, et al., Plasma deoxycholic acid is related to deoxycholic acid in faecal water. Cancer Lett 1997; 114(1-2): 293-4. https://doi.org/10.1016/S0304-3835(97)04683-1
  41. Bayerdorffer E, Mannes GA, Richter WO, et al., Increased serum deoxycholic acid levels in men with colorectal adenomas. Gastroenterology 1993; 104(1): 145-51. https://doi.org/10.1016/0016-5085(93)90846-5
  42. Martinez JD, Stratagoules ED, LaRue JM, et al., Different bile acids exhibit distinct biological effects: the tumor promoter deoxycholic acid induces apoptosis and the chemopreventive agent ursodeoxycholic acid inhibits cell proliferation. Nutr Cancer 1998; 31(2): 111-8. https://doi.org/10.1080/01635589809514689
  43. Wachs FP, Krieg RC, Rodrigues CM, et al., Bile saltinduced 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(2): 103-13. https://doi.org/10.1007/s00384-004-0616-2
  44. Payne CM, Waltmire CN, Crowley C, et al., Caspase-6 mediated cleavage of guanylate cyclase alpha 1 during deoxycholate-induced apoptosis: protective role of the nitric oxide signaling module. Cell Biol Toxicol 2003; 19(6): 373-92. https://doi.org/10.1023/B:CBTO.0000013331.70391.0e
  45. Nobuoka A, Takayama T, Miyanishi K, et al., Glutathione-S-transferase P1-1 protects aberrant crypt foci from apoptosis induced by deoxycholic acid. Gastroenterology 2004; 127(2): 428-43. https://doi.org/10.1053/j.gastro.2004.05.021
  46. Tong JL, Ran ZH, Shen J, et al., Association between fecal bile acids and colorectal cancer: a meta-analysis of observational studies. Yonsei Med J 2008; 49(5): 792-803. https://doi.org/10.3349/ymj.2008.49.5.792
  47. Buchwald H, Varco RL, Boen JR, et al., Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias. Arch Intern Med 1998; 158(11): 1253-61. https://doi.org/10.1001/archinte.158.11.1253
  48. Buchwald H, Varco RL, Matts JP, et al., Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990; 323(14): 946-55. https://doi.org/10.1056/NEJM199010043231404
  49. Jess T, Winther KV, Munkholm P, et al., Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Aliment Pharmacol Ther 2004; 19(3): 287-93. https://doi.org/10.1111/j.1365-2036.2004.01858.x