从高脂血症大鼠模型大、小肠菌群改变探讨肠道菌群与高脂血症的关系
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摘要
目的：观察饮食性高脂血症大鼠大、小肠菌群变化，比较抗生素干预组与益生菌干预组血脂升高情况，探讨肠道菌群潜在的调脂作用。
方法：50只SD大鼠随机均分为5组，A组喂养普通饲料，B、C、D、E组喂养高脂饲料，B组(抗生素干预组)于实验第1天起予甲硝唑、诺氟沙星灌胃建立肠道菌群缺陷模型，C组为阳性对照组，D(菌株1干预组)、E(菌株2干预组)于第15天起分别予菌株1、2灌胃，第30天观察结果。第1天、第15天、第30天取大鼠粪便行菌群分析；第1天、第30天测量血脂指标。第30天处死大鼠，取小肠内容物行菌群分析。
结果：高脂饲料组(B、C、E)血胆固醇、LDL较其初始值明显增高，ΔTC明显高于A组(P＜0.05)。但菌株1干预组(D组)TC、TG增高较初始值无统计学意义，且ΔTC较A组无统计学差异。B、C、E组体重较A、D组明显增高(P＜0.05)，D组较A组无显著增高(P＞0.05)。高脂饮食组大便菌群发生明显改变，嗜酸乳杆菌、双歧杆菌、肠球菌计数明显降低(P＜0.05)，拟杆菌呈现“先增后降”趋势(P＜0.05)。小肠菌群相对稳定，C组拟杆菌较A组明显降低(P＜0.05)，D组小肠拟杆菌、肠球菌、大肠杆菌、金葡菌较A组明显降低(P＜0.05)。
结论：1.1％胆固醇、5％鲜猪油、10％蛋黄粉、0.2％胆酸钠、84％基础饲料混合制成的高脂饲料连续喂养SD大鼠30天可建立高胆固醇、LDL—胆固醇血症模型。2．高脂饮食(30天)可导致肠道菌群结构的改变，以大肠菌群为主，这种改变可能反过来进一步促进高脂血症的发展。3．菌株1可能具有降血脂、抑制脂肪蓄积的潜在益生菌功效，作用点可能位于小肠。
Objective:To observe the changes of both large intestinal and smallintestinal flora of hyperlipidemia SD rats, compare the elevation of serumlipid of antibiotics intervention group and bacteria strain interventiongroup in order to approach the latent capability in accommodating serumlipid of intestinal flora.
Method:50 SD rats were randomly divided into 5 groups. Group Awere normally fed,while Group B、C、D、E were fed by forage rich in oiland fat. Group B received antibiotics intervention by arilin andnorfloxacin intragastric administration from the 1st day on. Group D andE had been receiving intragastric administration of bacteriaⅠandⅡrespectively since the 15th day. We analyse the fecal microbial populationat the 1st day, the 15th day, and the 30th day, survey the serum lipid at the 1stand the 30th day. On the 30th day, we executed the rats and analyse thesmall intestinal flora.
Results:The level of TC、LDL was elevated significantly inGroupB、C、E compared to its primary concentration,the increment ofTC(ΔTC) in these groups was higher than GroupA (P＜0.05) .InGroupD,the elevation of TC、TG was not significant as well asΔTC(P＞0.05).The increase of bodyweight in GroupB、C、E was significantlyhigher than GroupA, while GroupD was not apparently higher thanGroupA (P＞0.05) .The fecal microbial population changed a lot in GroupB、C、D、E,the counts of Lactobacillus acidophilus、Bifidobacteria、Enterococci was significantly decreased,the counts of Bacteroides wasalso decreased after a increasing period (P＜0.05) .The small intestinalflora was relatively stable,with just Bacteroides decreased in GroupC. Butin groupD,the counts of Bacteroides、Enterococci、Escherichia coli andStaphylococcus aureus was significantly decreased compared to GroupA.
Conclusion:
1.Feeding the SD rats with mixed forage made of 1% cholesterol、5% animal oil、10%egg yolk powder、0.2% Sodium Cholate and 84% basicforages for 30 days can establish hyperlipidemia rats model.
2.High lipid diet intake for 30 days can result in the changes ofintestinal flora which mainly occurred in large intestine and wasconsidered to possibly accelerate the development of hyperlipidemia.
3.Bacteria strain I may have the latent ability to affect lipid and fatmetabolism in small intestine,and was considered to be a candidateprobiotic.
方法：50只SD大鼠随机均分为5组，A组喂养普通饲料，B、C、D、E组喂养高脂饲料，B组(抗生素干预组)于实验第1天起予甲硝唑、诺氟沙星灌胃建立肠道菌群缺陷模型，C组为阳性对照组，D(菌株1干预组)、E(菌株2干预组)于第15天起分别予菌株1、2灌胃，第30天观察结果。第1天、第15天、第30天取大鼠粪便行菌群分析；第1天、第30天测量血脂指标。第30天处死大鼠，取小肠内容物行菌群分析。
结果：高脂饲料组(B、C、E)血胆固醇、LDL较其初始值明显增高，ΔTC明显高于A组(P＜0.05)。但菌株1干预组(D组)TC、TG增高较初始值无统计学意义，且ΔTC较A组无统计学差异。B、C、E组体重较A、D组明显增高(P＜0.05)，D组较A组无显著增高(P＞0.05)。高脂饮食组大便菌群发生明显改变，嗜酸乳杆菌、双歧杆菌、肠球菌计数明显降低(P＜0.05)，拟杆菌呈现“先增后降”趋势(P＜0.05)。小肠菌群相对稳定，C组拟杆菌较A组明显降低(P＜0.05)，D组小肠拟杆菌、肠球菌、大肠杆菌、金葡菌较A组明显降低(P＜0.05)。
结论：1.1％胆固醇、5％鲜猪油、10％蛋黄粉、0.2％胆酸钠、84％基础饲料混合制成的高脂饲料连续喂养SD大鼠30天可建立高胆固醇、LDL—胆固醇血症模型。2．高脂饮食(30天)可导致肠道菌群结构的改变，以大肠菌群为主，这种改变可能反过来进一步促进高脂血症的发展。3．菌株1可能具有降血脂、抑制脂肪蓄积的潜在益生菌功效，作用点可能位于小肠。
Objective:To observe the changes of both large intestinal and smallintestinal flora of hyperlipidemia SD rats, compare the elevation of serumlipid of antibiotics intervention group and bacteria strain interventiongroup in order to approach the latent capability in accommodating serumlipid of intestinal flora.
Method:50 SD rats were randomly divided into 5 groups. Group Awere normally fed,while Group B、C、D、E were fed by forage rich in oiland fat. Group B received antibiotics intervention by arilin andnorfloxacin intragastric administration from the 1st day on. Group D andE had been receiving intragastric administration of bacteriaⅠandⅡrespectively since the 15th day. We analyse the fecal microbial populationat the 1st day, the 15th day, and the 30th day, survey the serum lipid at the 1stand the 30th day. On the 30th day, we executed the rats and analyse thesmall intestinal flora.
Results:The level of TC、LDL was elevated significantly inGroupB、C、E compared to its primary concentration,the increment ofTC(ΔTC) in these groups was higher than GroupA (P＜0.05) .InGroupD,the elevation of TC、TG was not significant as well asΔTC(P＞0.05).The increase of bodyweight in GroupB、C、E was significantlyhigher than GroupA, while GroupD was not apparently higher thanGroupA (P＞0.05) .The fecal microbial population changed a lot in GroupB、C、D、E,the counts of Lactobacillus acidophilus、Bifidobacteria、Enterococci was significantly decreased,the counts of Bacteroides wasalso decreased after a increasing period (P＜0.05) .The small intestinalflora was relatively stable,with just Bacteroides decreased in GroupC. Butin groupD,the counts of Bacteroides、Enterococci、Escherichia coli andStaphylococcus aureus was significantly decreased compared to GroupA.
Conclusion:
1.Feeding the SD rats with mixed forage made of 1% cholesterol、5% animal oil、10%egg yolk powder、0.2% Sodium Cholate and 84% basicforages for 30 days can establish hyperlipidemia rats model.
2.High lipid diet intake for 30 days can result in the changes ofintestinal flora which mainly occurred in large intestine and wasconsidered to possibly accelerate the development of hyperlipidemia.
3.Bacteria strain I may have the latent ability to affect lipid and fatmetabolism in small intestine,and was considered to be a candidateprobiotic.
引文
1. Hjermann, I., K. Byre, and I. Holme. 1981. Effect of diet and smoking intervention on the incidence of coronary heart disease. Lancet ii: 1303.
2. Guarner, F., and G. Schaafsma. 1998. Probiotics. Int. J. Food Microbiol. 39:237-238.
3. Mercenier, A., S. Pavan, and B. Pot. 2003. Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr. Pharm. Des. 8:99-110.
4. Reid, G., J. Jass, M. T. Sebulsky, and J. K. McCormick. 2003. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 16:658-672.
5. Shanahan, F. 2003. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv. Drug Deliv. Rev. 56:809-818.
6. Shaper, A.G., Jones, K.W., Jones, M., and Kyobe, J. 1963. Serum lipids in three nomadic tribes of northern Kenya. American J. Clin. Nutrit. 13: 135-146.
7. Mann, G.V. 1974. Studies of a surfactant and cholesterolemia in the Maasai. Am. J. Clin. Nutrit. 27: 464-469.
8. Pereira D I A, Gibson G R. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut. Appl Environ Microbiol, 2002,68:4689-46931
9. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85: 3182-31881.
10. Dambekodi P C, Gilliland S E. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J Dairy Sci, 1998,81: 1818-18241
11. Klaver F A M, R van der Meer. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt2deconjugating activity. Appl Environ Microbiol, 1993,59: 1120-11241.
12. Gilliland S E , Nelson C R , Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol, 1985, 49:377-3811.
13. Tahri K, Grill J P, Schneider F. Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria. Current Microbiology, 1997, 34: 79-841
14. Pcreira D I A , McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521.
15. Mc Auliffe, O., R. J. Cano, and T. R. Klaenhammer. 2005. Genetic analysis of two bile salt hydrolase activities in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 71:4925-4929.
16. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
17. Kim, G. B., M. Brochet, and B. H. Lee. 2005. Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium adolescentis. Biotechnol. Lett. 27: 817-822.
18. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
19. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881.
20. Pereira D I A , McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521.
21. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
22. Tahri, K., Grill, J. P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
23. De Rodas, B.Z., Gilliland, S.E., and Maxweell,C.V. 1996. Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in swine with hypocholesterolemia induced by diet. J. Dairy Sci. 79:2121-2128.
24. Gilliland, S.E., Nelson, C.R., and Maxwell, C. 1985. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 49: 377-381.
25. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881.
26. E. I. Psomas*, D. J. Fletourist, E. Litopoulou-Tzanetaki* and N. Tzanetakis. 2003.Assimilation of Cholesterol by Yeast Strains Isolated from Infant Feces and Feta Cheese. J. Dairy Sci. 86:3416-3422
27. M. T. Liong and N. P. Shah.2005. Acid and Bile Tolerance and Cholesterol Removal Ability of Lactobacilli Strains. J. Dairy Sci. 88:55-66
28. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
29. Tahri, K., Grill, J.P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
30. Fuller, R. and Gibson, G. 1998. Probiotics and prebiotics. In: Encyclopaedia of Food Microbiology. pp. 1633-1639, Academic Press.
31. 84. St-Onge, M. P., Farnworth, E.R., and Jones,P.J.H. 2000. Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism.Am. J. Clin. Nutrit. 71: 674-681.
32. Dora I. A. Pereira,* Anne L. McCartney, and Glenn R. Gibson.2003. An In Vitro Study of the Probiotic Potential of a Bile-Salt-Hydrolyzing Lactobacillus fermentum Strain, and Determination of Its Cholesterol-Lowering Properties. Applied and Environmental Microbiology, August 2003, Vol. 69, No.8,p:4743-4752.
33. FernandezM L, Wilson T A,Conde K, et al. Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein,soluble fiber or cholesterol content. J Nutr,1999,129(7):1323.
34. Kris-Etherton PM and D iteschy J.Design criteria fostudies examing individual fatty acid effects on cardio vascular disease risk factors:human and animal studies.Am J Clin Nutr, 1997,65(supp 1):1549.
35. Laue, H., M. Friedrich, J. Ruff, and A. M. Cook. 2001. Dissimilatory sulfite reductase (desulfoviridin) of the taurine-degrading, non-sulfate-reducing bacterium Bilophila wadsworthia RZATAU contains a fused DsrB-DsrD subunit. J. Bacteriol. 183: 1727-1733.
36. Deplancke, B., and H. R. Gaskins. 2003. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 17: 1310-1312.
37. Maire Begley, 1,2 Colin Hill,1,2 and Cormac G. M. Gahanl.2006. Bile Salt Hydrolase Activity in Probiotics. Applied and Environmental Microbiology. Vol. 72, No．3，p：1729-1738．
38．刘祥．张朝武．潘素华．裴晓方．余倩．2005．不同体脂人群肠道主要菌群的定量分析．卫生研究．Vol．34，No．6，P：724-725．
39．王芳．房建伟．2005．高脂血症大鼠肠道菌群变化的试验研究．黑龙江医药科学．Aug．Vol．28．No4．P：52-53．
40. Fredrik B, Hao D, Ting W, et al. The gut microbiota as an environmental factor that regulates fat storage. PNAS, 2004, 101(44): 15718215723.
1. Lipid Research Clinics Program 1984. The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. J. Am. Med. Assoc. 251: 351-363.
2. Journal of the American Medical Association. 1984. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 251:351-363.
3. Levine, G. N., J. F. Keaney, and J. A. Vita. 1995. Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N. Engl. J. Med. 332:512-521.
4. Hjermann, I., K. Byre, and I. Holme. 1981. Effect of diet and smoking intervention on the incidence of coronary heart disease. Lancet ii:1303.
5. Guarner, F., and G. Schaafsma. 1998. Probiotics. Int. J. Food Microbiol. 39:237-238.
6. Mercenier, A., S. Pavan, and B. Pot. 2003. Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr. Pharm. Des. 8:99-110.
7. Reid, G., J. Jass, M. T. Sebulsky, and J. K. McCormick. 2003. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 16:658-672.
8. Shanahan, F. 2003. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv. Drug Deliv. Rev. 56:809-818.
9. Shaper, A.G., Jones, K.W., Jones, M., and Kyobe, J. 1963. Serum lipids in three nomadic tribes of northern Kenya. American J. Clin. Nutrit. 13: 135-146.
10. Mann, G.V. 1974. Studies of a surfactant and cholesterolemia in the Maasai. Am. J. Clin. Nutrit. 27: 464-469.
11. Harrison, V.C. and Peat, G. 1975. Serum cholesterol and bowel flora in the newborn. Am. J. Clin. Nutrit. 28: 1351-1355.
12. Howard, A.N. and Marks, J. 1977. Hypocholesterolemic effect of milk. Lancet 2: 957.
13. Hepner, G., Fried, R., Jeor, S. St., Fusetti, L.and Morin, R. 1979. Hypocholesterolemic effect of yoghurt and milk. Am. J. Clin. Nutrit. 32: 19-24.
14. Rossouw, J.E., Burger, E.M., Van der Vyer, P.and Ferreira, J.J. 1981. The effect of skim milk, yoghurt and full cream milk on human serum lipids. Am. J. Clin. Nutrit. 34: 351-356.
15. Agerbaek, M., Gerdes, L.U., and Richelsen, B.1995. Hypocholesterolemic effect of a new fermented milk product in healthy middleaged men. Eur. J. Clin. Nutrit. 49: 346-352.
16. Schaafsma, G., Meuling, W.J.A., van Dokkum, W., and Bouley, C. 1998. Effects of a milk product, fermented by Lactobacillus acidophilus and withfructo-oligosaccharides added, on blood lipids in male volunteers. Eur. J. Clin. Nutrit. 52: 436-440.
17. Bertolami, M.C., Faludi, A.A., and Batlouni, M.1999. Evaluation of the effects of a new fermented milk product (Gaio) on primary hypercholesterolemia. Eur. J. Clin. Nutrit. 53: 97-101.
18. Larsen, L.A., Raben, A., Haulrik, N., Hansen, A.S., Manders, M., and Astrop, A. 2000. Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur. J. Clin. Nutrit. 54: 288-297.
19. Schaarmann, G., Schneider, J., Zorn, A., Vilser,C., and Jahreis, G. 2001. Influence of probiotic yoghurt on serum lipids in women. Am. J. Clin. Nutrit. 73(Suppl.): 496S.
20. Gilliland, S. E., Nelson, C.R., and Maxwell, C. 1985. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 49: 377-381.
21. Gilliland, S.E. and Walker, D.K. 1990. Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. J. Dairy Sci. 73: 905-911.
22. Walker, D.K. and Gilliland, S.E. 1993. Relationships among bile tolerance, bile salt deconjugation and assimilation of cholesterol by Lactobacillus acidophilus. J. Dairy Sci. 76: 956-961.
23. Rasic, J. L., Vujcic, I. F., Skrinjar, M., and Vulic, M. 1992. Assimilation of cholesterol by some cultures of lactic acid bacteria and bifidobacteria. Biotechnol Lett 14: 39-44.
24. Buck L M, Gilliland S E. Comparisons of freshly isolated strains of Lactobacillus acidophilus of human intestinal origin for ability to assimilate cholesterol during growth. J Dairy Sci, 1994,77: 2925-29331
25. Tahri K, Grill J P, Schneider F. Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria. Current Microbiology, 1997, 34: 79-841
26. Pereira D I A, McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521
27. Pereira D I A, Gibson G R. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut . Appl Environ Microbiol, 2002, 68: 4689-46931
28. Dambekodi P C, Gilliland S E. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J Dairy Sci, 1998,81:1818-1824
29. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
30. Tahri, K., Grill, J.P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
31. Carey, M. C., and W. C. Duane. 1994. Enterohepatic circulation, p. 719-738. In I. M. Arias, N. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter, and D. A. Shafritz (ed.), The liver: biology and pathobiology. Raven Press, Ltd., New York, N.Y.
32. De Rodas, B.Z., Gilliland, S.E., and Maxweell,C. V. 1996. Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in swine with hypocholesterolemia induced by diet. J. Dairy Sci. 79: 2121-2128.
33. Christiaens, H., R. J. Leer, P. H. Pouwels, and W. Verstraete. 1992. Cloning and expression of a conjugated bile acid hydrolase gene from Lactobacillus plantarum by using a direct plate assay. Appl. Environ. Microbiol. 58:3792-3798.
34. Corzo, G., and S. E. Gilliland. 1999. Measurement of bile salt hydrolase activity from Lactobacillus acidophilus based on disappearance of conjugated bile salts. J. Dairy Sci. 82:466-471.
35. Gilliland, S. E., and M. J. Speck. 1977. Deconjugation of bile acids by intestinal lactobacilli. Appl. Environ. Microbiol. 33:15-18.
36. De Smet, I., L. Van Hoorde, M. Vande Woestyne, H. Christiaens, and W. Verstraete. 1995. Significance of bile salt hydrolytic activities of lactobacilli. J. Appl. Bacteriol. 79: 292-301.
37. Grill, J. P., S. Perrin, and F. Schneider. 2000. Bile toxicity to some bifidobacteria strains: role of conjugated bile salt hydrolase and pH. Can. J. Microbiol. 46:878-884.
38. Grill, J. P., F. Schneider, J. Crociani, and J. Ballongue. 1995. Purification and characterization of conjugated bile salt hydrolase from Bifidobacterium longum BB536. Appl. Environ. Microbiol. 61:2577-2582.
39. Tanaka, H., H. Hashiba, J. Kok, and I. Mierau. 2000. Bile salt hydrolase of Bifidobacterium longum: biochemical and genetic characterization. Appl. Environ. Microbiol. 66:2502-2512.
40. Taranto, M. P., and G. Font de Valdez. 1999. Localization and primary characterization of bile salt hydrolase from Lactobacillus reuteri. Biotechnol. Lett. 21:935-938.
41. Bateup, J. M., M. A. McConnell, H. F. Jenkinson, and G. W. Tannock. 1995. Comparison of Lactobacillus strains with respect to bile salt hydrolase activity, colonization of the gastrointestinal tract, and growth rate of the murine host. Appl. Environ. Microbiol. 61:1147-1149.
42. Dashkevicz, M. P., and S. D. Feighner. 1989. Development of a differential medium for bile salt hydrolase-active Lactobacillus spp. Appl. Environ. Microbiol. 55:11-16.
43. De Boever, P., and W. Verstraete. 1999. Bile salt deconjugation by Lactobacillus plantarum 80 and its implication for bacterial toxicity. J. Appl. Microbiol. 87:345-352.
44. Elkins, C. A., S. A. Moser, and D. C. Savage. 2001. Genes encoding bile salt hydrolases and conjugated bile salt transporters in Lactobacillus johnsonii 100-100 and other Lactobacillus species. Microbiology 147:3403-3412.
45. Grill, J. P., C. Cayuela, J. M. Antoine, and F. Schneider. 2000. Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistance. J. Appl. Microbiol. 89:553-563.
46. Mc Auliffe, O., R. J. Cano, and T. R. Klaenhammer. 2005. Genetic analysis of two bile salt hydrolase activities in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 71:4925-4929.
47. Tanaka, H., K. Doesburg, T. Iwasaki, and I. Mierau. 1999. Screening of lactic acid bacteria for bile salt hydrolase activity. J. Dairy Sci. 82:2530-2535.
48. Kim, G. B., and B. H. Lee. 2005. Biochemical and molecular insights into bile salt hydrolase in the gastrointestinal microflora: a review. Asian-Aust. J. Anim. Sci. 18: 1505-1512.
49. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
50. Kim, G. B., M. Brochet, and B. H. Lee. 2005. Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium adolescentis. Biotechnol. Lett. 27:817-822.
51. Franz, C. M. A. P., I. Specht, P. Haberer, and W. H. Holzapfel. 2001. Bile salt hydrolase activity of enterococci isolated from food: screening and quantitative determination. J. Food Prot. 64:725-729.
52. Knarreborg, A., R. M. Engberg, S. K. Jensen, and B. B. Jensen. 2002. Quantitative determination of bile salt hydrolase activity in bacteria isolated from the small intestine of chickens. Appl. Environ. Microbiol. 68:6425-6428.
53. Wijaya, A., A. Hermann, H. Abriouel, I. Specht, N. M. Yousif, W. H. Holzapfel, and C. M. Franz. 2004. Cloning of the bile salt hydrolase (bsh) gene from Enterococcus faecium FAIR-E-345 and chromosomal location of bsh genes in food enterococci. J. Food Prot. 67:2772-2778.
54. Coleman, J. P., and L. L. Hudson. 1995. Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens. Appl. Environ. Microbiol. 61:2514-2520.
55. Pereira, D. I., A. L. McCartney, and G. R. Gibson. 2003. An in vitro study of the probiotic potential of a bile-salt-hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol-lowering properties. Appl. Environ. Microbiol. 69:4743-4752.
56. Kawamoto, K., I. Horibe, and K. Uchida. 1989. Purification and characterization of a new hydrolase for conjugated bile acids, chenodeoxycholyltaurine hydrolase, from Bacteroides vulgatus. J. Biochem. 106:1049-1053.
57. Stellwag, E. J., and P. B. Hylemon. 1976. Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp, fragilis. Biochim. Biophys. Acta 452:165-176.
58. Ahn, Y. T., G. B. Kim, Y. S. Lim, Y. J. Baek, and Y. U. Kim. 2003. Deconjugation of bile salts by Lactobacillus acidophilus isolates. Int. Dairy J. 13:303-311.
59. Hylemon, P. B., and T. L. Glass. 1983. Bile acid and cholesterol metabolism. In Human Intestinal Microflora in Health and Disease. D. J. Henteges, editor. Academic Press, New York. 189-213.
60. Huijghebaert, S. M., J. A. Mertens, and H. J. Eyssen. 1982. Isolation of a bile salt sulfatase-producing Clostridium strain from rat intestinal microflora. Appl. Environ. Microbiol. 43:185-192.
61. Van Eldere, J., P. Celis, G. De Pauw, E. Lesaffre, and H. Eyssen. 1996. Tauroconjugation of cholic acid stimulates 7α-dehydroxylation by fecal bacteria. Appl. Environ. Microbiol. 62:656-661.
62. Gilliland, S. E., and M. J. Speck. 1977. Deconjugation of bile acids by intestinal lactobacilli. Appl. Environ. Microbiol. 33:15-18.
63. Tannock, G. W., M. P. Dashkevicz, and S. D. Feighner. 1989. Lactobacilli and bile salt hydrolase in the murine intestinal tract. Appl. Environ. Microbiol. 55:1848-1851.
64. Boggs, J. M. 1987. Lipid intermolecular hydrogen bonding: influence on structural organization and membrane function. Biochim. Biophys. Acta 906:353-404.
65. Dambekodi, P. C., and S. E. Gilliland. 1998. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J. Dairy Sci. 81:1818-1824.
66. Taranto, M. P., M. L. Fernandez Murga, G. Lorca, and G. Font de Valdez. 2003. Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteri. J. Appl. Microbiol. 95:86-91.
67. Hofmann, A. F. 1994. Bile acids, p. 677-718. In I. M. Arias, J. L. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter, and D. A. Shafritz (ed.), The liver: biology and pathobiology. Raven Press, Ltd., New York, N.Y.
68. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
69. Coleman, J. P., and L. L. Hudson. 1995. Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens. Appl. Environ. Microbiol. 61: 2514-2520
70. Gopal, A., N. P. Shah, and H. Roginski. 1996. Bile tolerance, taurocholate deconjugation, and cholesterol removal by Lactobacillus acidophilus and Bifidobacterium spp. Milchwissenschafl 51:619-623.
71. Moser, S. A., and D. C. Savage. 2001. Bile salt hydrolase activity and resistance to toxicity of conjugated bile salts are unrelated properties in lactobacilli. Appl. Environ. Microbiol. 67:3476-3480.
72. Taranto, M. P., F. Sesma, A. P. Ruiz Holgado, and G. Font de Valdez. 1997. Bile salt hydrolase plays a key role on cholesterol removal by Lactobacillus reuteri. Biotechnol. Lett. 19:845-847.
73. Usman (The United Graduate School of Agricultural Science), and A. Hosono. 1999. Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains. J. Dairy Sci. 82:243-248.
74. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881
75. Tahri, K., Crociani, J., Ballongue, J., and Schneider, F. 1995. Effects of three strains of bifidobacteria on cholesterol. Lett. Appl.Microbiol. 21: 149-151.
76. Noh, D.O., Kim, S.H., and Gilliland, S.E. 1997.Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121. J. Dairy Sci. 80:3107-3113.
77. Usman and Hosono, A. 1999. Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains. J. Dairy Sci. 82: 243-248.
78. E. I. Psomas*, D. J. Fletourist, E. Litopoulou-Tzanetaki* and N. Tzanetakis. 2003.Assimilation of Cholesterol by Yeast Strains Isolated from Infant Feces and Feta Cheese. J. Dairy Sci. 86:3416-3422
79. M. T. Liong and N. P. Shah.2005. Acid and Bile Tolerance and Cholesterol Removal Ability of Lactobacilli Strains. J. Dairy Sci. 88:55-66
80. Fuller, R. and Gibson, G. 1998. Probiotics and prebiotics. In: Encyclopaedia of Food Microbiology. pp. 1633-1639, Academic Press.
81. Gibson, G. 1999. Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin. J. Nutrit. 129:1438S-1441S.
82. Fiordaliso, M., Kok, N., Desaher, J.P., Goethals,F., Deboyser, D., Roberfroid, M., andDelzenne, N. 1995. Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 30: 163-167.
83. Kok, N., Roberfroid, M., Robert, A., and Delzenne, N. 1996. Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats. Br. J. Nutrit.76: 881-890.
84. St-Onge, M. P., Farnworth, E.R., and Jones,P.J.H. 2000. Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism.Am. J. Clin. Nutrit. 71: 674-681.
85. Wolever, T.M.S., Fernandes, J., and Veketeshwer Rao, A. 1996. Serum acetate: propionate ratio is related to serum cholesterol in men but not in women. J. Nutrit. 126: 2790-2797.
86. Dora I. A. Pereira,* Anne L. McCartney, and Glenn R. Gibson.2003. An In Vitro Study of the Probiotic Potential of a Bile-Salt-Hydrolyzing Lactobacillus fermentum Strain, and Determination of Its Cholesterol-Lowering Properties. Applied and Environmental Microbiology, August 2003, Vol. 69, No.8,p:4743-4752
87．张建忠．低脂肪和低胆固醇食品开发．食品科技．1997(6)：11—12
88. Bjorkhem,I.,Gustafsson,J-A.Mechanism of microbial transformation of cholesterol into coprostanol European Journal of Biochemistry, 1971(21): 428-432
89. Owen,R.W.,Tennesson,M.E.and Bilton,R.R.,et al. The degradation of cholesterol by Escherichia coli isolated from human faeces.Biochemistry Social Translation,1978(6):377-379
90. Owen,T.W.,Mason,A.N.and Bilton,R.F.The degradation of cholesterol by pseudomonas species NCIB 10590 under aerobic conditions.Journal of Lipid Research, 1983(24): 1500-1511
91. Peter Kurdi, Hendrik W. van Veen, Hiroshi Tanaka, Igor Mierau, Wil N. Konings, Gerald W. Tannock,Fusao Tomita, and Atsushi Yokota.2000. Cholic Acid Is Accumulated Spontaneously, Driven by Membrane ApH, in Many Lactobacilli. Journal of Bacteriology, Vol. 182, No. 22 p. 6525-6528.
92. Peter Kurdi, Hiroshi Tanaka, Hendrik W. van Veen , Kozo Asano, Fusao Tomita and Atsushi Yokota.2003. Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria.Microbiology 149 (2003),p:2031-2037
93. R. M. Pigeon2, E. P. Cuesta and S. E. Gilliland. Binding of Free Bile Acids by Cells of Yogurt Starter Culture Bacteria. J. Dairy Sci. 85:2705-2710
94. Vanhoof, K. and De Schrijver, R. 1995. Effect of unprocessed and baked inulin on lipid metabolism in normo- and hypercholesterolemic rats. Nutrit. Res. 15: 1637-1646.
95. Trautwein, E.A., Rieckhoff, D., and Erbersdobler,H.F. 1998. Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J. Nutrit.128: 1937-1943.
96. Laue, H., M. Friedrich, J. Ruff, and A. M. Cook. 2001. Dissimilatory sulfite reductase (desulfoviridin) of the taurine-degrading, non-sulfate-reducing bacterium Bilophila wadsworthia RZATAU contains a fused DsrB-DsrD subunit. J. Bacteriol. 183: 1727-1733.
97. Lie, T. J., M. L. Clawson, W. Godchaux, and E. R. Leadbetter. 1999. Sulfidogenesis from 2-aminoethanesulfonate (taurine) fermentation by a morphologically unusual sulfate-reducing bacterium, Desulforhopalus singaporensis sp. nov. Appl. Environ. Microbiol. 65: 3328-3334.
98. Christi, S. U., H. D. Eisner, G. Dusel, H. Kasper, and W. Scheppach. 1996. Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis. Dig. Dis. Sci. 41: 2477-2481.
99. Deplancke, B., and H. R. Gaskins. 2003. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 17: 1310-1312.
100. Jason M. Ridlon, Dae-Joong Kang and Phillip B. Hylemon.2006. Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research, Vol. 47, 241-259
101. Bernstein, C., H. Bernstein, C. M. Payne, K. Dvorakova, and H. Garewal. 2005. Bile acids as carcinogens in human gastrointestinal cancers. Mutat. Res. 589:47-65.
102. Kandell, R. L., and C. Bernstein. 1991. Bile salt/acid induction of DNA damage in bacterial and mammalian cells: implications for colon cancer, Nutr. Cancer 16:227-238.
103. Marteau, P., M. F. Gehard, A. Myara, E. Bouvier, F. Trivin, and J. C. Rambaud. 1995. Metabolism of bile salts by alimentary bacteria during transit in the human small intestine. Microb. Ecol. Health Dis. 8:151-157.
104. Nagengast, F. M., M. J. Grobben, and I. P. Van Munster. 1995. Role of bile acids in colorectal carcinogenesis. Eur. J. Cancer 31:1067-1070.
105. Pazzi, P., A. C. Puriani, M. Dalla Libera, G. Guerra, D. Rici, S. Gullini, and C. Ottolenghi. 1997. Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in vitro study in perfused rat hepatocytes. Eur. J. Gastroenterol. Hepatol. 9:703-709.
106. Jones, M. L., H. Chen, W. Ouyang, T. Metz, and S. Prakash. 2004. Microencapsulated genetically engineered Lactobacillus plantarum 80 (pCBH1) for bile acid deconjugation and its implication in lowering cholesterol. J. Biomed. Biotechnol. 1:61-69.
107. Kurdi, P., H. Tanaka, H. W. van Veen, K. Asano, F. Tomita, and A. Yokota. 2003. Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria. Microbiology 149:2031-2037.
108. Kurdi, P., H. W. van Veen, H. Tanaka, I. Mierau, W. N. Konings, G. W. Tannock, F. Tomita, and A. Yokota. 2000. Cholic acid is accumulated spontaneously, driven by membrane ApH, in many lactobacilli. J. Bacteriol. 182:6525-6528.
2. Guarner, F., and G. Schaafsma. 1998. Probiotics. Int. J. Food Microbiol. 39:237-238.
3. Mercenier, A., S. Pavan, and B. Pot. 2003. Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr. Pharm. Des. 8:99-110.
4. Reid, G., J. Jass, M. T. Sebulsky, and J. K. McCormick. 2003. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 16:658-672.
5. Shanahan, F. 2003. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv. Drug Deliv. Rev. 56:809-818.
6. Shaper, A.G., Jones, K.W., Jones, M., and Kyobe, J. 1963. Serum lipids in three nomadic tribes of northern Kenya. American J. Clin. Nutrit. 13: 135-146.
7. Mann, G.V. 1974. Studies of a surfactant and cholesterolemia in the Maasai. Am. J. Clin. Nutrit. 27: 464-469.
8. Pereira D I A, Gibson G R. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut. Appl Environ Microbiol, 2002,68:4689-46931
9. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85: 3182-31881.
10. Dambekodi P C, Gilliland S E. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J Dairy Sci, 1998,81: 1818-18241
11. Klaver F A M, R van der Meer. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt2deconjugating activity. Appl Environ Microbiol, 1993,59: 1120-11241.
12. Gilliland S E , Nelson C R , Maxwell C. Assimilation of cholesterol by Lactobacillus acidophilus. Appl Environ Microbiol, 1985, 49:377-3811.
13. Tahri K, Grill J P, Schneider F. Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria. Current Microbiology, 1997, 34: 79-841
14. Pcreira D I A , McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521.
15. Mc Auliffe, O., R. J. Cano, and T. R. Klaenhammer. 2005. Genetic analysis of two bile salt hydrolase activities in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 71:4925-4929.
16. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
17. Kim, G. B., M. Brochet, and B. H. Lee. 2005. Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium adolescentis. Biotechnol. Lett. 27: 817-822.
18. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
19. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881.
20. Pereira D I A , McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521.
21. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
22. Tahri, K., Grill, J. P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
23. De Rodas, B.Z., Gilliland, S.E., and Maxweell,C.V. 1996. Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in swine with hypocholesterolemia induced by diet. J. Dairy Sci. 79:2121-2128.
24. Gilliland, S.E., Nelson, C.R., and Maxwell, C. 1985. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 49: 377-381.
25. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881.
26. E. I. Psomas*, D. J. Fletourist, E. Litopoulou-Tzanetaki* and N. Tzanetakis. 2003.Assimilation of Cholesterol by Yeast Strains Isolated from Infant Feces and Feta Cheese. J. Dairy Sci. 86:3416-3422
27. M. T. Liong and N. P. Shah.2005. Acid and Bile Tolerance and Cholesterol Removal Ability of Lactobacilli Strains. J. Dairy Sci. 88:55-66
28. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
29. Tahri, K., Grill, J.P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
30. Fuller, R. and Gibson, G. 1998. Probiotics and prebiotics. In: Encyclopaedia of Food Microbiology. pp. 1633-1639, Academic Press.
31. 84. St-Onge, M. P., Farnworth, E.R., and Jones,P.J.H. 2000. Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism.Am. J. Clin. Nutrit. 71: 674-681.
32. Dora I. A. Pereira,* Anne L. McCartney, and Glenn R. Gibson.2003. An In Vitro Study of the Probiotic Potential of a Bile-Salt-Hydrolyzing Lactobacillus fermentum Strain, and Determination of Its Cholesterol-Lowering Properties. Applied and Environmental Microbiology, August 2003, Vol. 69, No.8,p:4743-4752.
33. FernandezM L, Wilson T A,Conde K, et al. Hamsters and guinea pigs differ in their plasma lipoprotein cholesterol distribution when fed diets varying in animal protein,soluble fiber or cholesterol content. J Nutr,1999,129(7):1323.
34. Kris-Etherton PM and D iteschy J.Design criteria fostudies examing individual fatty acid effects on cardio vascular disease risk factors:human and animal studies.Am J Clin Nutr, 1997,65(supp 1):1549.
35. Laue, H., M. Friedrich, J. Ruff, and A. M. Cook. 2001. Dissimilatory sulfite reductase (desulfoviridin) of the taurine-degrading, non-sulfate-reducing bacterium Bilophila wadsworthia RZATAU contains a fused DsrB-DsrD subunit. J. Bacteriol. 183: 1727-1733.
36. Deplancke, B., and H. R. Gaskins. 2003. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 17: 1310-1312.
37. Maire Begley, 1,2 Colin Hill,1,2 and Cormac G. M. Gahanl.2006. Bile Salt Hydrolase Activity in Probiotics. Applied and Environmental Microbiology. Vol. 72, No．3，p：1729-1738．
38．刘祥．张朝武．潘素华．裴晓方．余倩．2005．不同体脂人群肠道主要菌群的定量分析．卫生研究．Vol．34，No．6，P：724-725．
39．王芳．房建伟．2005．高脂血症大鼠肠道菌群变化的试验研究．黑龙江医药科学．Aug．Vol．28．No4．P：52-53．
40. Fredrik B, Hao D, Ting W, et al. The gut microbiota as an environmental factor that regulates fat storage. PNAS, 2004, 101(44): 15718215723.
1. Lipid Research Clinics Program 1984. The lipid research clinics coronary primary prevention trial results. I. Reduction in incidence of coronary heart disease. J. Am. Med. Assoc. 251: 351-363.
2. Journal of the American Medical Association. 1984. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA 251:351-363.
3. Levine, G. N., J. F. Keaney, and J. A. Vita. 1995. Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N. Engl. J. Med. 332:512-521.
4. Hjermann, I., K. Byre, and I. Holme. 1981. Effect of diet and smoking intervention on the incidence of coronary heart disease. Lancet ii:1303.
5. Guarner, F., and G. Schaafsma. 1998. Probiotics. Int. J. Food Microbiol. 39:237-238.
6. Mercenier, A., S. Pavan, and B. Pot. 2003. Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr. Pharm. Des. 8:99-110.
7. Reid, G., J. Jass, M. T. Sebulsky, and J. K. McCormick. 2003. Potential uses of probiotics in clinical practice. Clin. Microbiol. Rev. 16:658-672.
8. Shanahan, F. 2003. Probiotics in inflammatory bowel disease: therapeutic rationale and role. Adv. Drug Deliv. Rev. 56:809-818.
9. Shaper, A.G., Jones, K.W., Jones, M., and Kyobe, J. 1963. Serum lipids in three nomadic tribes of northern Kenya. American J. Clin. Nutrit. 13: 135-146.
10. Mann, G.V. 1974. Studies of a surfactant and cholesterolemia in the Maasai. Am. J. Clin. Nutrit. 27: 464-469.
11. Harrison, V.C. and Peat, G. 1975. Serum cholesterol and bowel flora in the newborn. Am. J. Clin. Nutrit. 28: 1351-1355.
12. Howard, A.N. and Marks, J. 1977. Hypocholesterolemic effect of milk. Lancet 2: 957.
13. Hepner, G., Fried, R., Jeor, S. St., Fusetti, L.and Morin, R. 1979. Hypocholesterolemic effect of yoghurt and milk. Am. J. Clin. Nutrit. 32: 19-24.
14. Rossouw, J.E., Burger, E.M., Van der Vyer, P.and Ferreira, J.J. 1981. The effect of skim milk, yoghurt and full cream milk on human serum lipids. Am. J. Clin. Nutrit. 34: 351-356.
15. Agerbaek, M., Gerdes, L.U., and Richelsen, B.1995. Hypocholesterolemic effect of a new fermented milk product in healthy middleaged men. Eur. J. Clin. Nutrit. 49: 346-352.
16. Schaafsma, G., Meuling, W.J.A., van Dokkum, W., and Bouley, C. 1998. Effects of a milk product, fermented by Lactobacillus acidophilus and withfructo-oligosaccharides added, on blood lipids in male volunteers. Eur. J. Clin. Nutrit. 52: 436-440.
17. Bertolami, M.C., Faludi, A.A., and Batlouni, M.1999. Evaluation of the effects of a new fermented milk product (Gaio) on primary hypercholesterolemia. Eur. J. Clin. Nutrit. 53: 97-101.
18. Larsen, L.A., Raben, A., Haulrik, N., Hansen, A.S., Manders, M., and Astrop, A. 2000. Effect of 8 week intake of probiotic milk products on risk factors for cardiovascular diseases. Eur. J. Clin. Nutrit. 54: 288-297.
19. Schaarmann, G., Schneider, J., Zorn, A., Vilser,C., and Jahreis, G. 2001. Influence of probiotic yoghurt on serum lipids in women. Am. J. Clin. Nutrit. 73(Suppl.): 496S.
20. Gilliland, S. E., Nelson, C.R., and Maxwell, C. 1985. Assimilation of cholesterol by Lactobacillus acidophilus. Appl. Environ. Microbiol. 49: 377-381.
21. Gilliland, S.E. and Walker, D.K. 1990. Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans. J. Dairy Sci. 73: 905-911.
22. Walker, D.K. and Gilliland, S.E. 1993. Relationships among bile tolerance, bile salt deconjugation and assimilation of cholesterol by Lactobacillus acidophilus. J. Dairy Sci. 76: 956-961.
23. Rasic, J. L., Vujcic, I. F., Skrinjar, M., and Vulic, M. 1992. Assimilation of cholesterol by some cultures of lactic acid bacteria and bifidobacteria. Biotechnol Lett 14: 39-44.
24. Buck L M, Gilliland S E. Comparisons of freshly isolated strains of Lactobacillus acidophilus of human intestinal origin for ability to assimilate cholesterol during growth. J Dairy Sci, 1994,77: 2925-29331
25. Tahri K, Grill J P, Schneider F. Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria. Current Microbiology, 1997, 34: 79-841
26. Pereira D I A, McCartney A L, Gibson G R. An in vitro study of the probiotic potential of a bile2salt2hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol21owering properties. Appl Environ Microbiol, 2003, 69:4743-47521
27. Pereira D I A, Gibson G R. Cholesterol assimilation by lactic acid bacteria and bifidobacteria isolated from the human gut . Appl Environ Microbiol, 2002, 68: 4689-46931
28. Dambekodi P C, Gilliland S E. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J Dairy Sci, 1998,81:1818-1824
29. Klaver, F.A.M., and van der Meer, R. 1993. The assumed assimilation of cholesterol by lactobacilli and Bifidobacterium bifidum is due to their bile salt-deconjugating activity. Appl. Environ. Microbiol. 59:1120-1124.
30. Tahri, K., Grill, J.P., and Schneider, F. 1996.Bifidobacteria strain behaviour toward cholesterol: coprecipitation with bile salts and assimilation. Curr. Microbiol. 33: 187-193.
31. Carey, M. C., and W. C. Duane. 1994. Enterohepatic circulation, p. 719-738. In I. M. Arias, N. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter, and D. A. Shafritz (ed.), The liver: biology and pathobiology. Raven Press, Ltd., New York, N.Y.
32. De Rodas, B.Z., Gilliland, S.E., and Maxweell,C. V. 1996. Hypocholesterolemic action of Lactobacillus acidophilus ATCC 43121 and calcium in swine with hypocholesterolemia induced by diet. J. Dairy Sci. 79: 2121-2128.
33. Christiaens, H., R. J. Leer, P. H. Pouwels, and W. Verstraete. 1992. Cloning and expression of a conjugated bile acid hydrolase gene from Lactobacillus plantarum by using a direct plate assay. Appl. Environ. Microbiol. 58:3792-3798.
34. Corzo, G., and S. E. Gilliland. 1999. Measurement of bile salt hydrolase activity from Lactobacillus acidophilus based on disappearance of conjugated bile salts. J. Dairy Sci. 82:466-471.
35. Gilliland, S. E., and M. J. Speck. 1977. Deconjugation of bile acids by intestinal lactobacilli. Appl. Environ. Microbiol. 33:15-18.
36. De Smet, I., L. Van Hoorde, M. Vande Woestyne, H. Christiaens, and W. Verstraete. 1995. Significance of bile salt hydrolytic activities of lactobacilli. J. Appl. Bacteriol. 79: 292-301.
37. Grill, J. P., S. Perrin, and F. Schneider. 2000. Bile toxicity to some bifidobacteria strains: role of conjugated bile salt hydrolase and pH. Can. J. Microbiol. 46:878-884.
38. Grill, J. P., F. Schneider, J. Crociani, and J. Ballongue. 1995. Purification and characterization of conjugated bile salt hydrolase from Bifidobacterium longum BB536. Appl. Environ. Microbiol. 61:2577-2582.
39. Tanaka, H., H. Hashiba, J. Kok, and I. Mierau. 2000. Bile salt hydrolase of Bifidobacterium longum: biochemical and genetic characterization. Appl. Environ. Microbiol. 66:2502-2512.
40. Taranto, M. P., and G. Font de Valdez. 1999. Localization and primary characterization of bile salt hydrolase from Lactobacillus reuteri. Biotechnol. Lett. 21:935-938.
41. Bateup, J. M., M. A. McConnell, H. F. Jenkinson, and G. W. Tannock. 1995. Comparison of Lactobacillus strains with respect to bile salt hydrolase activity, colonization of the gastrointestinal tract, and growth rate of the murine host. Appl. Environ. Microbiol. 61:1147-1149.
42. Dashkevicz, M. P., and S. D. Feighner. 1989. Development of a differential medium for bile salt hydrolase-active Lactobacillus spp. Appl. Environ. Microbiol. 55:11-16.
43. De Boever, P., and W. Verstraete. 1999. Bile salt deconjugation by Lactobacillus plantarum 80 and its implication for bacterial toxicity. J. Appl. Microbiol. 87:345-352.
44. Elkins, C. A., S. A. Moser, and D. C. Savage. 2001. Genes encoding bile salt hydrolases and conjugated bile salt transporters in Lactobacillus johnsonii 100-100 and other Lactobacillus species. Microbiology 147:3403-3412.
45. Grill, J. P., C. Cayuela, J. M. Antoine, and F. Schneider. 2000. Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistance. J. Appl. Microbiol. 89:553-563.
46. Mc Auliffe, O., R. J. Cano, and T. R. Klaenhammer. 2005. Genetic analysis of two bile salt hydrolase activities in Lactobacillus acidophilus NCFM. Appl. Environ. Microbiol. 71:4925-4929.
47. Tanaka, H., K. Doesburg, T. Iwasaki, and I. Mierau. 1999. Screening of lactic acid bacteria for bile salt hydrolase activity. J. Dairy Sci. 82:2530-2535.
48. Kim, G. B., and B. H. Lee. 2005. Biochemical and molecular insights into bile salt hydrolase in the gastrointestinal microflora: a review. Asian-Aust. J. Anim. Sci. 18: 1505-1512.
49. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
50. Kim, G. B., M. Brochet, and B. H. Lee. 2005. Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium adolescentis. Biotechnol. Lett. 27:817-822.
51. Franz, C. M. A. P., I. Specht, P. Haberer, and W. H. Holzapfel. 2001. Bile salt hydrolase activity of enterococci isolated from food: screening and quantitative determination. J. Food Prot. 64:725-729.
52. Knarreborg, A., R. M. Engberg, S. K. Jensen, and B. B. Jensen. 2002. Quantitative determination of bile salt hydrolase activity in bacteria isolated from the small intestine of chickens. Appl. Environ. Microbiol. 68:6425-6428.
53. Wijaya, A., A. Hermann, H. Abriouel, I. Specht, N. M. Yousif, W. H. Holzapfel, and C. M. Franz. 2004. Cloning of the bile salt hydrolase (bsh) gene from Enterococcus faecium FAIR-E-345 and chromosomal location of bsh genes in food enterococci. J. Food Prot. 67:2772-2778.
54. Coleman, J. P., and L. L. Hudson. 1995. Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens. Appl. Environ. Microbiol. 61:2514-2520.
55. Pereira, D. I., A. L. McCartney, and G. R. Gibson. 2003. An in vitro study of the probiotic potential of a bile-salt-hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol-lowering properties. Appl. Environ. Microbiol. 69:4743-4752.
56. Kawamoto, K., I. Horibe, and K. Uchida. 1989. Purification and characterization of a new hydrolase for conjugated bile acids, chenodeoxycholyltaurine hydrolase, from Bacteroides vulgatus. J. Biochem. 106:1049-1053.
57. Stellwag, E. J., and P. B. Hylemon. 1976. Purification and characterization of bile salt hydrolase from Bacteroides fragilis subsp, fragilis. Biochim. Biophys. Acta 452:165-176.
58. Ahn, Y. T., G. B. Kim, Y. S. Lim, Y. J. Baek, and Y. U. Kim. 2003. Deconjugation of bile salts by Lactobacillus acidophilus isolates. Int. Dairy J. 13:303-311.
59. Hylemon, P. B., and T. L. Glass. 1983. Bile acid and cholesterol metabolism. In Human Intestinal Microflora in Health and Disease. D. J. Henteges, editor. Academic Press, New York. 189-213.
60. Huijghebaert, S. M., J. A. Mertens, and H. J. Eyssen. 1982. Isolation of a bile salt sulfatase-producing Clostridium strain from rat intestinal microflora. Appl. Environ. Microbiol. 43:185-192.
61. Van Eldere, J., P. Celis, G. De Pauw, E. Lesaffre, and H. Eyssen. 1996. Tauroconjugation of cholic acid stimulates 7α-dehydroxylation by fecal bacteria. Appl. Environ. Microbiol. 62:656-661.
62. Gilliland, S. E., and M. J. Speck. 1977. Deconjugation of bile acids by intestinal lactobacilli. Appl. Environ. Microbiol. 33:15-18.
63. Tannock, G. W., M. P. Dashkevicz, and S. D. Feighner. 1989. Lactobacilli and bile salt hydrolase in the murine intestinal tract. Appl. Environ. Microbiol. 55:1848-1851.
64. Boggs, J. M. 1987. Lipid intermolecular hydrogen bonding: influence on structural organization and membrane function. Biochim. Biophys. Acta 906:353-404.
65. Dambekodi, P. C., and S. E. Gilliland. 1998. Incorporation of cholesterol into the cellular membrane of Bifidobacterium longum. J. Dairy Sci. 81:1818-1824.
66. Taranto, M. P., M. L. Fernandez Murga, G. Lorca, and G. Font de Valdez. 2003. Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteri. J. Appl. Microbiol. 95:86-91.
67. Hofmann, A. F. 1994. Bile acids, p. 677-718. In I. M. Arias, J. L. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter, and D. A. Shafritz (ed.), The liver: biology and pathobiology. Raven Press, Ltd., New York, N.Y.
68. Kim, G. B., C. M. Miyamoto, E. A. Meighen, and B. H. Lee. 2004. Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidium strains. Appl. Environ. Microbiol. 70:5603-5612.
69. Coleman, J. P., and L. L. Hudson. 1995. Cloning and characterization of a conjugated bile acid hydrolase gene from Clostridium perfringens. Appl. Environ. Microbiol. 61: 2514-2520
70. Gopal, A., N. P. Shah, and H. Roginski. 1996. Bile tolerance, taurocholate deconjugation, and cholesterol removal by Lactobacillus acidophilus and Bifidobacterium spp. Milchwissenschafl 51:619-623.
71. Moser, S. A., and D. C. Savage. 2001. Bile salt hydrolase activity and resistance to toxicity of conjugated bile salts are unrelated properties in lactobacilli. Appl. Environ. Microbiol. 67:3476-3480.
72. Taranto, M. P., F. Sesma, A. P. Ruiz Holgado, and G. Font de Valdez. 1997. Bile salt hydrolase plays a key role on cholesterol removal by Lactobacillus reuteri. Biotechnol. Lett. 19:845-847.
73. Usman (The United Graduate School of Agricultural Science), and A. Hosono. 1999. Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains. J. Dairy Sci. 82:243-248.
74. Kimoto H, Ohmomo S, Okamoto T. Cholesterol removal from media by lactococci. J Dairy Sci, 2002,85:3182-31881
75. Tahri, K., Crociani, J., Ballongue, J., and Schneider, F. 1995. Effects of three strains of bifidobacteria on cholesterol. Lett. Appl.Microbiol. 21: 149-151.
76. Noh, D.O., Kim, S.H., and Gilliland, S.E. 1997.Incorporation of cholesterol into the cellular membrane of Lactobacillus acidophilus ATCC 43121. J. Dairy Sci. 80:3107-3113.
77. Usman and Hosono, A. 1999. Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains. J. Dairy Sci. 82: 243-248.
78. E. I. Psomas*, D. J. Fletourist, E. Litopoulou-Tzanetaki* and N. Tzanetakis. 2003.Assimilation of Cholesterol by Yeast Strains Isolated from Infant Feces and Feta Cheese. J. Dairy Sci. 86:3416-3422
79. M. T. Liong and N. P. Shah.2005. Acid and Bile Tolerance and Cholesterol Removal Ability of Lactobacilli Strains. J. Dairy Sci. 88:55-66
80. Fuller, R. and Gibson, G. 1998. Probiotics and prebiotics. In: Encyclopaedia of Food Microbiology. pp. 1633-1639, Academic Press.
81. Gibson, G. 1999. Dietary modulation of the human gut microflora using the prebiotics oligofructose and inulin. J. Nutrit. 129:1438S-1441S.
82. Fiordaliso, M., Kok, N., Desaher, J.P., Goethals,F., Deboyser, D., Roberfroid, M., andDelzenne, N. 1995. Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 30: 163-167.
83. Kok, N., Roberfroid, M., Robert, A., and Delzenne, N. 1996. Involvement of lipogenesis in the lower VLDL secretion induced by oligofructose in rats. Br. J. Nutrit.76: 881-890.
84. St-Onge, M. P., Farnworth, E.R., and Jones,P.J.H. 2000. Consumption of fermented and nonfermented dairy products: effects on cholesterol concentrations and metabolism.Am. J. Clin. Nutrit. 71: 674-681.
85. Wolever, T.M.S., Fernandes, J., and Veketeshwer Rao, A. 1996. Serum acetate: propionate ratio is related to serum cholesterol in men but not in women. J. Nutrit. 126: 2790-2797.
86. Dora I. A. Pereira,* Anne L. McCartney, and Glenn R. Gibson.2003. An In Vitro Study of the Probiotic Potential of a Bile-Salt-Hydrolyzing Lactobacillus fermentum Strain, and Determination of Its Cholesterol-Lowering Properties. Applied and Environmental Microbiology, August 2003, Vol. 69, No.8,p:4743-4752
87．张建忠．低脂肪和低胆固醇食品开发．食品科技．1997(6)：11—12
88. Bjorkhem,I.,Gustafsson,J-A.Mechanism of microbial transformation of cholesterol into coprostanol European Journal of Biochemistry, 1971(21): 428-432
89. Owen,R.W.,Tennesson,M.E.and Bilton,R.R.,et al. The degradation of cholesterol by Escherichia coli isolated from human faeces.Biochemistry Social Translation,1978(6):377-379
90. Owen,T.W.,Mason,A.N.and Bilton,R.F.The degradation of cholesterol by pseudomonas species NCIB 10590 under aerobic conditions.Journal of Lipid Research, 1983(24): 1500-1511
91. Peter Kurdi, Hendrik W. van Veen, Hiroshi Tanaka, Igor Mierau, Wil N. Konings, Gerald W. Tannock,Fusao Tomita, and Atsushi Yokota.2000. Cholic Acid Is Accumulated Spontaneously, Driven by Membrane ApH, in Many Lactobacilli. Journal of Bacteriology, Vol. 182, No. 22 p. 6525-6528.
92. Peter Kurdi, Hiroshi Tanaka, Hendrik W. van Veen , Kozo Asano, Fusao Tomita and Atsushi Yokota.2003. Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria.Microbiology 149 (2003),p:2031-2037
93. R. M. Pigeon2, E. P. Cuesta and S. E. Gilliland. Binding of Free Bile Acids by Cells of Yogurt Starter Culture Bacteria. J. Dairy Sci. 85:2705-2710
94. Vanhoof, K. and De Schrijver, R. 1995. Effect of unprocessed and baked inulin on lipid metabolism in normo- and hypercholesterolemic rats. Nutrit. Res. 15: 1637-1646.
95. Trautwein, E.A., Rieckhoff, D., and Erbersdobler,H.F. 1998. Dietary inulin lowers plasma cholesterol and triacylglycerol and alters biliary bile acid profile in hamsters. J. Nutrit.128: 1937-1943.
96. Laue, H., M. Friedrich, J. Ruff, and A. M. Cook. 2001. Dissimilatory sulfite reductase (desulfoviridin) of the taurine-degrading, non-sulfate-reducing bacterium Bilophila wadsworthia RZATAU contains a fused DsrB-DsrD subunit. J. Bacteriol. 183: 1727-1733.
97. Lie, T. J., M. L. Clawson, W. Godchaux, and E. R. Leadbetter. 1999. Sulfidogenesis from 2-aminoethanesulfonate (taurine) fermentation by a morphologically unusual sulfate-reducing bacterium, Desulforhopalus singaporensis sp. nov. Appl. Environ. Microbiol. 65: 3328-3334.
98. Christi, S. U., H. D. Eisner, G. Dusel, H. Kasper, and W. Scheppach. 1996. Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis. Dig. Dis. Sci. 41: 2477-2481.
99. Deplancke, B., and H. R. Gaskins. 2003. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 17: 1310-1312.
100. Jason M. Ridlon, Dae-Joong Kang and Phillip B. Hylemon.2006. Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research, Vol. 47, 241-259
101. Bernstein, C., H. Bernstein, C. M. Payne, K. Dvorakova, and H. Garewal. 2005. Bile acids as carcinogens in human gastrointestinal cancers. Mutat. Res. 589:47-65.
102. Kandell, R. L., and C. Bernstein. 1991. Bile salt/acid induction of DNA damage in bacterial and mammalian cells: implications for colon cancer, Nutr. Cancer 16:227-238.
103. Marteau, P., M. F. Gehard, A. Myara, E. Bouvier, F. Trivin, and J. C. Rambaud. 1995. Metabolism of bile salts by alimentary bacteria during transit in the human small intestine. Microb. Ecol. Health Dis. 8:151-157.
104. Nagengast, F. M., M. J. Grobben, and I. P. Van Munster. 1995. Role of bile acids in colorectal carcinogenesis. Eur. J. Cancer 31:1067-1070.
105. Pazzi, P., A. C. Puriani, M. Dalla Libera, G. Guerra, D. Rici, S. Gullini, and C. Ottolenghi. 1997. Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in vitro study in perfused rat hepatocytes. Eur. J. Gastroenterol. Hepatol. 9:703-709.
106. Jones, M. L., H. Chen, W. Ouyang, T. Metz, and S. Prakash. 2004. Microencapsulated genetically engineered Lactobacillus plantarum 80 (pCBH1) for bile acid deconjugation and its implication in lowering cholesterol. J. Biomed. Biotechnol. 1:61-69.
107. Kurdi, P., H. Tanaka, H. W. van Veen, K. Asano, F. Tomita, and A. Yokota. 2003. Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria. Microbiology 149:2031-2037.
108. Kurdi, P., H. W. van Veen, H. Tanaka, I. Mierau, W. N. Konings, G. W. Tannock, F. Tomita, and A. Yokota. 2000. Cholic acid is accumulated spontaneously, driven by membrane ApH, in many lactobacilli. J. Bacteriol. 182:6525-6528.