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Increasing ursodeoxycholic acid in the enterohepatic circulation of pigs through the administration of living bacteria

  • Pascale Lepercq (a1), Dominique Hermier (a2), Olivier David (a3), Rachel Michelin (a1), Clotilde Gibard (a1), Fabienne Beguet (a1), Purification Relano (a4), Chantal Cayuela (a4) and Catherine Juste (a1)...


We investigated the feasibility of increasing ursodeoxycholic acid (UDCA) in the enterohepatic circulation of pigs by administering living bacteria capable of epimerising endogenous amidated chenodeoxycholic acid (CDCA) to UDCA. We first demonstrated that combining Bifidobacterium animalis DN-173 010, as a bile salt-hydrolysing bacterium, and Clostridium absonum ATCC 27555, as a CDCA to UDCA epimerising bacterium, led to the efficient epimerisation of glyco- and tauro-CDCA in vitro, with respective UDCA yields of 55·8 (se 2·8) and 36·6 (se 1·5)%. This strain combination was then administered to hypercholesterolaemic pigs over a 3-week period, as two daily preprandial doses of either viable (six experimental pigs) or heat-inactivated bacteria (six controls). The main effects of treatment were on unconjugated bile acids (P=0·035) and UDCA (P<0·0001) absorbed into the portal vein, which increased 1·6–1·7- and 3·5–7·5-fold, respectively, under administration of living compared with inactivated bacteria. In bile, UDCA did not increase significantly, but the increase in biliary lithocholic acid with time in the controls was not observed in the experimental pigs (P=0·007), and the same trend was observed in faeces. All other variables (biliary lipid equilibrium, plasma lipid levels and partition of cholesterol between the different lipoprotein classes) remained unaffected by treatment throughout the duration of the experiment. In conclusion, it is feasible to increase the bioavailability of UDCA to the intestine and the liver by administering active bacteria. This may represent an interesting new probiotic activity, provided that in future it could be expressed by a safe food micro-organism.

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Corresponding author

*Corresponding author: Dr Catherine Juste, fax +33 1 34 65 24 92, email


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Agerholm-Larsen, L, Raben, A, Haulrik, N, Hansen, AS, Manders, M & Astrup, A (2000) Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur J Clin Nutr 54, 288297.
Aldini, R, Roda, A, Montagnani, M, Cerrè, C, Pellicciari, R & Roda, E (1996) Relationship between structure and intestinal absorption of bile acids with a steroid or side-chain modification. Steroids 61, 590597.
Bachrach, WH & Hofmann, AF (1982) Ursodeoxycholic acid treatment of cholesterol cholelithiasis Part II. Dig Dis Sci 27, 833856.
Baijal, PK, Fitzpatrick, DW & Bird, RP (1998) Comparative effects of secondary bile acids, deoxycholic and lithocholic acids, on aberrant crypt foci growth in the postinitiation phases of colon carcinogenesis. Nutr Cancer 31, 8189.
Baron, SF, Franklund, CV & Hylemon, PB (1991) Cloning, sequencing, and expression of the gene coding for bile acid 7α-hydroxysteroid dehydrogenase from Eubacterium sp. strain VPI 12708. J Bacteriol 173, 45584569.
Batta, AK, Salen, G, Holubec, H, Brasitus, TA, Alberts, D & Earnest, DL (1998) Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps. Cancer Res 58, 16841687.
Bennett, MJ, McKnight, SL & Coleman, JP (2003) Cloning and characterization of the NAD-dependent 7α-hydroxysteroid dehydrogenase from Bacteroides fragilis. Curr Microbiol 47, 475484.
Brown, I, Warhurst, M, Arcot, J, Playne, M, Illman, RJ & Topping, DL (1997) Fecal numbers of bifidobacteria are higher in pigs fed Bifidobacterium longum with a high amylose cornstarch than with a low amylose cornstarch. J Nutr 127, 18221827.
Chen, RM, Wu, JJ, Lee, SC, Huang, AH & Wu, HM (1999) Increase of intestinal Bifidobacterium and suppression of coliform bacteria with short-term yogurt ingestion. J Dairy Sci 82, 23082314.
Coleman, JP, Hudson, LL & Adams, MJ (1994) Characterization and regulation of the NADP-linked 7α-hydroxysteroid dehydrogenase gene from Clostridium sordellii. J Bacteriol 176, 48654874.
Colombo, C, Setchell, KD, Podda, M, Crosignani, A, Roda, A, Curcio, L, Ronchi, M & Giunta, A (1990) Effects of ursodeoxycholic acid therapy for liver disease associated with cystic fibrosis. J Pediatr 117, 482489.
Combes, B, Carithers, RL Jr, Maddrey, WC, Lin, D, McDonald, MF, Wheeler, DE, Eigenbrodt, EH, Munoz, SJ, Rubin, R & Garcia-Tsao, G (1995) A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology 22, 759766.
Crosignani, A, Setchell, KD, Invernizzi, P, Larghi, A, Rodrigues, CM & Podda, M (1996) Clinical pharmacokinetics of therapeutic bile acids. Clin Pharmacokinet 30, 333358.
De Rodas, BZ, Gilliland, SE & Maxwell, CV (1996) Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in swine with hypercholesterolemia induced by diet. J Dairy Sci 79, 21212128.
De Smet, I, De Boever, P & Verstraete, W (1998) Cholesterol lowering in pigs through enhanced bacterial bile salt hydrolase activity. Br J Nutr 79, 185194.
Drouault, S & Corthier, G (2001) Health effects of lactic acid bacteria ingested in fermented milk. Vet Res 32, 101117.
Drouault, S, Anba, J & Corthier, G (2002) Streptococcus thermophilus is able to produce a β-galactosidase active during its transit in the digestive tract of germ-free mice. Appl Environ Microbiol 68, 938941.
Earnest, DL, Holubec, H, Wali, RK, Jolley, CS, Bissonette, M, Bhattacharyya, AK, Roy, H, Khare, S & Brasitus, TA (1994) Chemoprevention of azoxymethane-induced colonic carcinogenesis by supplemented dietary ursodeoxycholic acid. Cancer Res 54, 50715074.
Ellis, E, Axelson, M, Abrahamsson, A, Eggertsen, G, Thorne, A, Nowak, G, Ericzon, BG, Bjorkhem, I & Einarsson, C (2003) Feedback regulation of bile acid synthesis in primary human hepatocytes: evidence that CDCA is the strongest inhibitor. Hepatology 38, 930938.
Fedorowski, T, Salen, G, Tint, GS & Mosbach, E (1979) Transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal bacteria. Gastroenterology 77, 10681073.
Ferezou, J, Riottot, M & Serougne, C, et al. (1997) Hypocholesterolemic action of β-cyclodextrin and its effects on cholesterol metabolism in pigs fed a cholesterol-enriched diet. J Lipid Res 38, 86100.
Fischer, S, Neubrand, M & Paumgartner, G (1993) Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine. Eur J Clin Invest 23, 2836.
Fossati, P & Prencipe, L (1982) Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28, 20772080.
Fujiwara, S, Seto, Y, Kimura, A & Hashiba, H (2001) Intestinal transit of an orally administered streptomycin-rifampicin-resistant variant of Bifidobacterium longum SBT2928: its long-term survival and effect on the intestinal microflora and metabolism. J Appl Microbiol 90, 4352.
Hayase, M, Mitsui, N, Tamai, K, Nakamura, S & Nishida, S (1974) Isolation of Clostridium absonum and its cultural and biochemical properties. Infect Immun 9, 1519.
Hirano, S, Nakama, R, Tamaki, M, Masuda, N & Oda, H (1981) Isolation and characterization of thirteen intestinal microorganisms capable of 7α-dehydroxylating bile acids. Appl Environ Microbiol 41, 737745.
Hungate, RE (1969) A roll tube method for cultivation of strict anaerobes. Methods Microbiol 3, 117132.
Invernizzi, P, Setchell, KD, Crosignani, A, Battezzati, PM, Larghi, A, O'Connell, NC & Podda, M (1999) Differences in the metabolism and disposition of ursodeoxycholic acid and its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology 29, 320327.
Juste, C, Corring, T & Le Coz, Y (1983) Bile restitution procedures for studying bile secretion in fistulated pigs. Lab Anim Sci 33, 199202.
Kenward, MG & Roger, JH (1997) Small sample inference for fixed effects from restricted maximum likelihood. Biometrics 53, 983997.
Kozoni, V, Tsioulias, G, Shiff, S & Rigas, B (2000) The effect of lithocholic acid on proliferation and apoptosis during the early stages of colon carcinogenesis: differential effect on apoptosis in the presence of a colon carcinogen. Carcinogenesis 21, 9991005.
Latta, RK, Fiander, H, Ross, NW, Simpson, C & Schneider, H (1993) Toxicity of bile acids to colon cancer cell lines. Cancer Lett 16, 167173.
Legrand-Defretin, V, Juste, C, Corring, T & Rerat, A (1986) Enterohepatic circulation of bile acids in pigs: diurnal pattern and effect of a reentrant biliary fistula. Am J Physiol 250, G295G301.
Lepercq, P, Gérard, P, Béguet, F, Raibaud, P, Grill, JP, Relano, P, Cayuela, C & Juste, C (2004a) Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces. FEMS Microbiol Lett 235, 6572.
Lepercq, P, Gérard, P, Béguet, F, Grill, JP, Relano, P, Cayuela, C & Juste, C (2004b) Isolates from normal human intestinal flora but not lactic acid bacteria exhibit 7α- and 7β-hydroxysteroid dehydrogenase activities. Microbial Ecol Health Dis 16, 195201.
Lepercq, P, Relano, P, Cayuela, C & Juste, C (2004c) Bifidobacterium animalis strain DN-173 010 hydrolyses bile salts in the gastrointestinal tract of pigs. Scand J Gastroenterol 39, 12661271.
Lindor, KD, Lacerda, MA, Jorgensen, RA, DeSotel, CK, Batta, AK, Salen, G, Dickson, ER, Rossi, SS & Hofmann, AF (1998) Relationship between biliary and serum bile acids and response to ursodeoxycholic acid in patients with primary biliary cirrhosis. Am J Gastroenterol 93, 14981504.
Macdonald, IA & Roach, PD (1981) Bile salt induction of 7α- and 7β-hydroxysteroid dehydrogenases in Clostridium absonum. Biochim Biophys Acta 665, 262269.
Macdonald, IA, Hutchison, DM & Forrest, TP (1981) Formation of urso- and ursodeoxy-cholic acids from primary bile acids by Clostridium absonum. J Lipid Res 22, 458466.
Marsh, A, Kim, DN, Lee, KT, Reiner, JM & Thomas, WA (1972) Cholesterol turnover, synthesis, and retention in hypercholesterolemic growing swine. J Lipid Res 13, 600615.
Nowak, G, Ungerstedt, J, Marschall, H-U, Einarsson, C & Ericzon, B-G (2001) Pre-treatment with ursodeoxycholic acid diminishes nonoxidative glycolysis in a pig liver transplantation model. Hepatology 34 294A
Oyama, K, Shiota, G, Ito, H, Murawaki, Y & Kawasaki, H (2002) Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats. Carcinogenesis 23, 885892.
Pereira, DI & Gibson, GR (2002) Effects of consumption of probiotics and prebiotics on serum lipid levels in humans. Crit Rev Biochem Mol Biol 37, 259281.
Pochart, P, Marteau, P, Bouhnik, Y, Goderel, I, Bourlioux, P & Rambaud, J-C (1992) Survival of bifidobacteria ingested via fermented milk during their passage through the human small intestine: an in vivo study using intestinal perfusion. Am J Clin Nutr 55, 7880.
Podda, M, Ghezzi, C, Battezzati, PM, Crosignani, A, Zuin, M & Roda, A (1990) Effects of ursodeoxycholic acid and taurine on serum liver enzymes and bile acids in chronic hepatitis. Gastroenterology 98, 10441050.
Ponz de Leon, M, Carulli, N, Loria, P, Iori, R & Zironi, F (1980) Cholesterol absorption during bile acid feeding: effect of ursodeoxycholic acid (UDCA) administration. Gastroenterology 78, 214219.
Poupon, RE, Ouguerram, K, Chrétien, Y, Verneau, C, Eschwège, E, Magot, T & Poupon, R (1993) Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. Hepatology 17, 577582.
Raicht, RF, Cohen, BI, Sarwal, A & Takahashi, M (1978) Ursodeoxycholic acid. Effects on sterol metabolism in rats. Biochim Biophys Acta 531, 18.
Reynier, MO, Montet, JC, Gerolami, A, Marteau, C, Crotte, C, Montet, AM & Mathieu, S (1981) Comparative effects of cholic, chenodeoxycholic, and ursodeoxycholic acids on micellar solubilization and intestinal absorption of cholesterol. J Lipid Res 22, 467473.
Richelsen, B, Kristensen, K & Pedersen, SB (1996) Long-term (6 months) effect of a new fermented milk product on the level of plasma lipoproteins – a placebo-controlled and double blind study. Eur J Clin Nutr 50, 811815.
Richmond, W (1973) Preparation and properties of a cholesterol oxidase from Nocardia sp. and its application to the enzymatic assay of total cholesterol in serum. Clin Chem 19, 13501356.
Riottot, M, Olivier, P, Huet, A, Caboche, J-J, Parquet, M, Khallou, J & Lutton, C (1993) Hypolipidemic effects of β-cyclodextrin in the hamster and in the genetically hypercholesterolemic Rico rat. Lipids 28, 181188.
Roberfroid, MB (2000) Prebiotics and probiotics: are they functional foods? Am J Clin Nutr 71, 1682S – 1687S discussion 1688S1690S.
Sarva, RP, Fromm, H, Carlson, GL, Mendelow, L & Ceryak, S (1980) Intracolonic conversion in man of chenodeoxycholic acid (CDC) to ursodeoxycholic acid (UDC) with and without formation of 7-keto lithocholic acid (KLC) as an intermediate. Gastroenterology 78, 1252 Abstr
Seraj, MJ, Umemoto, A, Kajikawa, A, Mimura, S, Kinouchi, T, Ohnishi, Y & Monden, Y (1997) Effects of dietary bile acids on formation of azoxymethane-induced aberrant crypt foci in F344 rats. Cancer Lett 115, 97103.
Shimizu, H, Yoshii, M, Seki, A, Une, M & Hoshita, T (1992) Hypocholesterolemic effect of ursodeoxycholylcysteic acid in hamsters fed a high cholesterol diet. J Pharmacobiodyn 15, 573580.
Simoni, P, Cerrè, C, Cipolla, A, Polimeni, C, Pistillo, A, Ceschel, G, Roda, E & Roda, A (1995) Bioavailability study of a new, sinking, enteric-coated ursodeoxycholic acid formulation. Pharmacol Res 31, 115119.
Sutherland, JD & Williams, CN (1985) Bile acid induction of 7α- and 7β-hydroxysteroid dehydrogenases in Clostridium limosum. J Lipid Res 26, 344350.
Takayama, M, Itoh, S, Nagasaki, T & Tanimizu, I (1977) A new enzymatic method for determination of serum choline-containing phospholipids. Clin Chim Acta 79, 9398.
Taranto, MP, Medici, M, Perdigon, G, Ruiz, Holgado AP & Valdez, GF (1998) Evidence for hypocholesterolemic effect of Lactobacillus reuteri in hypercholesterolemic mice. J Dairy Sci 81, 23362340.
Turley, SD & Dietschy, JM (1978) Re-evaluation of the 3α-hydroxysteroid dehydrogenase assay for total bile acids in bile. J Lipid Res 19, 924928.
Usman, HA (2001) Hypocholesterolemic effect of Lactobacillus gasseri SBT0270 in rats fed a cholesterol-enriched diet. J Dairy Res 68, 617624.
van Gorkom, BA, van der Meer, R, Boersma-van Ek, W, Termont, DS, de Vries, EG & Kleibeuker, JH (2002) Changes in bile acid composition and effect on cytolytic activity of fecal water by ursodeoxycholic acid administration: a placebo-controlled cross-over intervention trial in healthy volunteers. Scand J Gastroenterol 37, 965971.
Varnam, AH & Sutherland, JP (1994) Milk and Milk Products: Technology, Chemistry and Microbiology, 347380. London: Chapman & Hall.
Wali, RK, Stoiber, D, Nguyen, L, Hart, J, Sitrin, MD, Brasitus, T & Bissonnette, M (2002) Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumor development. Cancer Epidemiol Biomarkers Prev 11, 13161321.
Wang, X, Brown, IL, Evans, AJ & Conway, PL (1999) The protective effects of high amylose maize (amylomaize) starch granules on the survival of Bifidobacterium spp. in the mouse intestinal tract. J Appl Microbiol 87, 631639.
Woollett, LA, Buckley, DD, Yao, L, Jones, PJ, Granholm, NA, Tolley, EA & Heubi, JE (2003) Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans. J Lipid Res 44, 935942.
Xiao, JZ, Kondo, S, Takahashi, N, Miyaji, K, Oshida, K, Hiramatsu, A, Iwatsuki, K, Kokubo, S & Hosono, A (2003) Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers. J Dairy Sci 86, 24522461.
Yoshimoto, T, Higashi, H, Kanatani, A, Lin, XS, Nagai, H, Oyama, H, Kurazono, K & Tsuru, D (1991) Cloning and sequencing of the 7α-hydroxysteroid dehydrogenase gene from Escherichia coli HB 101 and characterization of the expressed enzyme. J Bacteriol 173, 21732179.


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Increasing ursodeoxycholic acid in the enterohepatic circulation of pigs through the administration of living bacteria

  • Pascale Lepercq (a1), Dominique Hermier (a2), Olivier David (a3), Rachel Michelin (a1), Clotilde Gibard (a1), Fabienne Beguet (a1), Purification Relano (a4), Chantal Cayuela (a4) and Catherine Juste (a1)...


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