Bile, Bacteria and Bears

Enterohepatic circulation is the process of secretion and reabsorption of bile (1;2). When you eat a fatty meal, your gallbladder secretes bile to convert large fat globules to small droplets called micelles to be absorbed (1;2). Ninety percent of the bile is then reabsorbed via active transport or passive transport in the small intestine (1). In the colon, bacteria increase the recycled amount by deconjugating some non-absorbable primary bile acids to secondary acids, which are then absorbed passively (1). Along with bile and its component of cholesterol, other molecules may be circulated.

For this reason, it is important to understand how fiber and bacteria affects enterohepatic circulation. Guar gum, for example, is a soluble fiber that may prevent postprandial increase of conjugated bile acids (3). Other fibers are found to have the same effect (4;5). By absorbing cholesterol and keeping it from re-entering enterohepatic circulation, guar gum and pectin (just as phytostanols and phytosterols) both can be helpful in reducing blood cholesterol (1;6;7). Fiber’s impact also appears to affect enterohepatic circulation of estrogens (8;9).

Prebiotic fiber and probiotics may be useful for drug therapy. One such drug is the secondary bile acid ursodeoxycholic acid (USDA). USDA lowers cholesterol and treats cholestatic liver disease (10-14). But because of how expensive it is to synthesize, the ancient and now illegal practice of “milking” black bears for their bile (which contains USDA) continues in China (15). If prebiotic fiber and probiotics can help recirculate the drug through enterohepatic circulation, it may result in becoming cheaper to use.

On the other hand, the intestinal flora can be detrimental when taken with other drugs. Because of enterohepatic circulation, active promotion of bacteria in recycling drugs can overload the liver and cause damage to the body (16). In such a case, antibiotics may be necessary. Doctors must take this potential toxicity into consideration when helping patients (16).
Lastly, other exogenous or endogenous xenobiotics (toxins) might be recycled by probiotic or pathogenic bacteria through enterohepatic circulation (17). In effect, the liver is performing double duty in such cases by detoxifying and detoxifying again (17). Depending on the situation, antibiotic and probiotic therapy may be needed.

References
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Roberts MS, Magnusson BM, Burczynski FJ, Weiss M. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet 2002;41:751-90.
3. Hansen WE, Maurer H, Vollmar J, Brauning C. Guar gum and bile: effects on postprandial gallbladder contraction and on serum bile acids in man. Hepatogastroenterology 1983;30:131-3.
4. Kern F, Jr., Birkner HJ, Ostrower VS. Binding of bile acids by dietary fiber. Am J Clin Nutr 1978;31:S175-S179.
5. Eastwood MA. Fibre and enterohepatic circulation. Nutr Rev 1977;35:42-4.
6. Fernandez ML, Trejo A, McNamara DJ. Pectin isolated from prickly pear (Opuntia sp.) modifies low density lipoprotein metabolism in cholesterol-fed guinea pigs. J Nutr 1990;120:1283-90.
7. Ebihara K, Schneeman BO. Interaction of bile acids, phospholipids, cholesterol and triglyceride with dietary fibers in the small intestine of rats. J Nutr 1989;119:1100-6.
8. Gorbach SL, Goldin BR. Diet and the excretion and enterohepatic cycling of estrogens. Prev Med 1987;16:525-31.
9. Adlercreutz H, Fotsis T, Bannwart C, Hamalainen E, Bloigu S, Ollus A. Urinary estrogen profile determination in young Finnish vegetarian and omnivorous women. J Steroid Biochem 1986;24:289-96.
10. Maeda K, Kambara M, Tian Y, Hofmann AF, Sugiyama Y. Uptake of ursodeoxycholate and its conjugates by human hepatocytes: role of Na(+)-taurocholate cotransporting polypeptide (NTCP), organic anion transporting polypeptide (OATP) 1B1 (OATP-C), and oatp1B3 (OATP8). Mol Pharm 2006;3:70-7.
11. Angelin B, Eusufzai S. Effects of ursodeoxycholic acid on plasma lipids. Scand J Gastroenterol Suppl 1994;204:24-6.
12. Hofmann AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scand J Gastroenterol Suppl 1994;204:1-15.
13. Rudolph G, Endele R, Senn M, Stiehl A. Effect of ursodeoxycholic acid on the kinetics of cholic acid and chenodeoxycholic acid in patients with primary sclerosing cholangitis. Hepatology 1993;17:1028-32.
14. Mazzella G, Parini P, Bazzoli F et al. Ursodeoxycholic acid administration on bile acid metabolism in patients with early stages of primary biliary cirrhosis. Dig Dis Sci 1993;38:896-902.
15. Feng Y, Siu K, Wang N et al. Bear bile: dilemma of traditional medicinal use and animal protection. J Ethnobiol Ethnomed 2009;5:2.
16. Mikov M. The metabolism of drugs by the gut flora. Eur J Drug Metab Pharmacokinet 1994;19:201-7.
17. Liska DJ. The detoxification enzyme systems. Altern Med Rev 1998;3:187-98.

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