FNS  Vol.3 No.2 , February 2012
Relationship of Dietary Soy Protein to Daidzein Metabolism by Cultures of Intestinal Microfloras from Monkeys
Abstract: Soybeans have been shown to contain larger concentrations of isoflavones than other plant foods. The colonic micro-floras of some individuals metabolize isoflavones, including the soy phytoestrogen daidzein, to compounds with altered estrogenic activity that may affect health. Monkeys have been used as models to predict the effect of colonic microorganisms on the metabolism of phytoestrogens. We studied the effect of consumption of a diet rich in soy protein on the metabolism of added daidzein by the intestinal microfloras of monkeys. The metabolism of daidzein by cultures of the colonic microfloras from eight males and eight females of Macaca fascicularis, 6 - 12 years old, consuming diets containing either soy or casein, and two males and three females of Macaca nemestrina, 3 - 5 months old, consuming infant formula, was investigated using high-performance liquid chromatographic analyses. Cultures from ten of the 16 adult monkeys and all five infant monkeys metabolized the added daidzein within 24 h. Daidzein was metabolized within 48 h by cultures from five other monkeys, but it remained even after 72 h in a culture from one female monkey on a casein diet. Equol and dihydrodaidzein were the only metabolites found. Individual variation among monkeys in the efficiency of daidzein metabolism was observed, but there appeared to be no correlation between diet and daidzein metabolism by the intestinal microflora. The intestinal microfloras of most monkeys tested were efficient in the biotransformation of daidzein to equol, regardless of the animals’ consumption of soy protein. Differences in the metabolism of isoflavones by the colonic microfloras of humans and experimental animals should be considered when extrapolating results from animals to humans.
Cite this paper: F. Rafii, J. Sutherland, B. Bridges, M. Park and M. Adams, "Relationship of Dietary Soy Protein to Daidzein Metabolism by Cultures of Intestinal Microfloras from Monkeys," Food and Nutrition Sciences, Vol. 3 No. 2, 2012, pp. 267-273. doi: 10.4236/fns.2012.32039.

[1]   S. E. Appt, “Usefulness of the Monkey Model to Investigate the Role of Soy in Postmenopausal Women’s Health,” Institute of Animal Research Journal, Vol. 45, No. 2, 2004, pp. 200-211.

[2]   S. E. Appt, R. T?rm?l?, A. A. Franke, T. S. Mikkola, M. J. Tikkanen, O. Ylikorkala and T. B. Clarkson, “Soy-Tibolone Combination—Effect on Lipids in Postmenopausal Monkeys and Women,” Maturitas, Vol. 60, No. 3-4, 2008, pp. 216-222. doi:10.1016/j.maturitas.2008.06.003

[3]   C. R. Cederroth and S. Nef, “Soy, Phytoestrogens and Metabolism: A Review,” Molecular and Cellular Endocrinology, Vol. 304, No. 1-2, 2009, pp. 30-42. doi:10.1016/j.mce.2009.02.027

[4]   R. T?rm?l?, S. Appt, T. B. Clarkson, P.-H. Groop, M. R?nnback, O. Ylikorkala and T. S. Mikkola, “Equol Production Capability Is Associated with Favorable Vascular Function in Postmenopausal Women Using Tibolone; No Effect with Soy Supplementation,” Atherosclerosis, Vol. 198, No. 1, 2008, pp. 174-178. doi:10.1016/j.atherosclerosis.2007.09.010

[5]   S. E. Walker, T. C. Register, S. E. Appt, M. R. Adams, T. B. Clarkson, H. Y. Chen, S. Isom, A. A. Franke and J. R. Kaplan, “Plasma Lipid-Dependent and -Independent Effects of Dietary Soy Protein and Social Status on Atherogenesis in Premenopausal Monkeys: Implications for Postmenopausal Atherosclerosis Burden,” Menopause, Vol. 15, No. 5, 2008, pp. 950-957. doi:10.1097/gme.0b013e3181612cef

[6]   L. Jian, “Soy Isoflavones and Prostate Cancer,” Molecular Nutrition and Food Research, Vol. 53, No. 2, 2009, pp. 217-226. doi:10.1002/mnfr.200800167

[7]   S. J. Kwack, K. B. Kim, H. S. Kim, K. S. Yoon and B. M. Lee, “Risk Assessment of Soybean-Based Phytoestrogens,” Journal of Toxicology and Environmental Health, Vol. 72, No. 21-22, 2009, pp. 1254-1261. doi:10.1080/15287390903212212

[8]   M.-S. Choi and K. C. Rhee, “Production and Processing of Soybeans and Nutrition and Safety of Isoflavone and Other Soy Products for Human Health,” Journal of Medicinal Food, Vol. 9, No. 1, 2006, pp. 1-10. doi:10.1089/jmf.2006.9.1

[9]   K. Morito, T. Hirose, J. Kinjo, T. Hirakawa, M. Okawa, T. Nohara, S. Ogawa, S. Inoue, S. M. Muramatsu and Y. Masamune, “Interaction of Phytoestrogens with Estrogen Receptors α and β,” Biological and Pharmaceutical Bulletin, Vol. 24, No. 4, 2001, pp. 351-356. doi:10.1248/bpb.24.351

[10]   J. Kinjo, R. Tsuchihashi, R. Morito, T. Hirose, T. Aomori, T. Nagao, H. Okabe, T. Nahora and Y. Masamune, “Interactions of Phytoestrogens with Estrogen Receptors α and β. III. Estrogenic Activities of Soy Isoflavone Aglycones and Their Metabolites Isolated from Human Urine,” Biological and Pharmaceutical Bulletin, Vol. 27, No. 2, 2004, pp. 185-188. doi:10.1248/bpb.27.185

[11]   H. G. Hur, J. O. Lay, R. D. Beger, J. P. Freeman and F. Rafii, “Isolation of Human Intestinal Bacteria Metabolizing the Natural Isoflavone Glycosides Daidzin and Genistin,” Archives of Microbiology, Vol. 174, No. 6, 2000, pp. 422-428. doi:10.1007/s002030000222

[12]   H. G. Hur and F. Rafii, “Biotransformation of the Isoflavonoids Biochanin A, Formononetin, and Glycitein by Eubacterium limosum,” FEMS Microbiology Letters, Vol. 192, No. 1, 2000, pp. 21-25. doi:10.1111/j.1574-6968.2000.tb09353.x

[13]   H. G. Hur, R. D. Beger, T. M. Heinze, J. O. Lay, J. P. Freeman, J. Dore and F. Rafii, “Isolation of an Anaerobic Intestinal Bacterium Capable of Cleaving the C-Ring of the Isoflavonoid Daidzein,” Archives of Microbiology, Vol. 178, No. 1, 2002, pp. 8-12. doi:10.1007/s00203-002-0414-6

[14]   F. Rafii, C. Davis, M. Park, T. M. Heinze and R. D. Beger, “Variations in Metabolism of the Soy Isoflavonoid Daidzein by Human Intestinal Microfloras from Different Individuals,” Archives of Microbiology, Vol. l80, No. 1, 2003, pp. 11-16.

[15]   F. Rafii, C. Hotchkiss, T. M. Heinze and M. Park, “Metabolism of Daidzein by Intestinal Bacteria from Rhesus Monkeys (Macaca mulatta),” Comparative Medicine, Vol. 54, No. 2, 2004, pp. 165-169.

[16]   H. J. Jou, S. C. Wu, F.-W. Chang, P. Y. Ling, K. S. Chu and W. H. Wu, “Effect of Intestinal Production of Equol on Menopausal Symptoms in Women Treated with Soy Isoflavones,” International Journal of Gynecology and Obstetrics, Vol. 102, No. 1, 2008, pp. 44-49. doi:10.1016/j.ijgo.2008.01.028

[17]   A. Matthies, M. Blaut and A. Braune, “Isolation of a Human Intestinal Bacterium Capable of Daidzein and Genistein Conversion,” Applied and Environmental Microbiology, Vol. 75, No. 6, 2009, pp. 1740-1744. doi:10.1128/AEM.01795-08

[18]   K. Hirayama, P. Baranczewski, J. E. Akerlund, T. Midtvedt, L. Moller and J. Rafter, “Effects of Human Intestinal Flora on Mutagenicity of and DNA Adduct Formation from Food and Environmental Mutagens,” Carcinogenesis, Vol. 21, No. 11, 2000, pp. 2105-2111. doi:10.1093/carcin/21.11.2105

[19]   L. Schoefer, R. Mohan, A. Braune, M. Birringer and M. Blaut, “Anaerobic C-Ring Cleavage of Genistein and Daidzein by Eubacterium ramulus,” FEMS Microbiology Letters, Vol. 208, No. 2, 2002, pp. 197-202. doi:10.1111/j.1574-6968.2002.tb11081.x

[20]   L. Schoefer, R. Mohan, A. Schwiertz, A. Braune and M. Blaut, “Anaerobic Degradation of Flavonoids by Clostridium orbiscindens,” Applied and Environmental Microbiology, Vol. 69, No. 10, 2003, pp. 5849-5854. doi:10.1128/AEM.69.10.5849-5854.2003

[21]   S. Yokoyama and T. Suzuki. “Isolation and Characterization of a Novel Equol-Producing Bacterium from Human Feces,” Bioscience Biotechnology and Biochemistry, Vol. 72, No. 10, 2008, pp. 2660-2666. doi:10.1271/bbb.80329

[22]   C. Gardana, E. Canzi and P.Simonetti, “The Role of Diet in the Metabolism of Daidzein by Human Faecal Microbiota Sampled from Italian Volunteers,” Journal of Nutritional Biochemistry, Vol. 20, No. 12, 2009, pp. 940-947. doi:10.1016/j.jnutbio.2008.08.006

[23]   Y. Mu?oz, A. Garrido and L. Valladares, “Equol Is More Active Than Soy Isoflavone Itself to Compete for Binding to Thromboxane A2 Receptor in Human Platelets,” Thrombosis Research, Vol. 123, No. 5, 2009, pp. 740744. doi:10.1016/j.thromres.2008.07.011

[24]   J. P. Yuan, J. H. Wang and X. Liu, “Metabolism of Dietary Soy Isoflavones to Equol by Human Intestinal Microflora—Implications for Health,” Molecular Nutrition and Food Research, Vol. 51, No. 7, 2007, pp. 765-781. doi:10.1002/mnfr.200600262

[25]   C. Atkinson, S. Berman, O. Humbert and J. W. Lampe, “In Vitro Incubation of Human Feces with Daidzein and Antibiotics Suggests Interindividual Differences in the Bacteria Responsible for Equol Production,” Journal of Nutrition, Vol. 134, No. 3, 2004, pp. 596-599.

[26]   K. A. Jackman, O. L. Woodman and C. G. Sobey, “Isoflavones, Equol and Cardiovascular Disease: Pharmacological and Therapeutic Insights,” Current Medicinal Chemistry, Vol. 14, No. 26, 2007, pp. 2824-2830. doi:10.2174/092986707782360178

[27]   M. S. Anthony, T. B. Clarkson, C. L. Hughes, T. M. Morgan and G. L. Burke, “Soybean Isoflavones Improve Cardiovascular Risk Factors without Affecting the Reproductive System of Peripubertal Rhesus Monkeys,” Journal of Nutrition, Vol. 26, No. 1, 1996, pp. 43-50.

[28]   M. Manjanatha, S. Shelton, M. Bishop, L. Lyn-Cook and A. Aidoo, “Dietary Effects of Soy Isoflavones Daidzein and Genistein on 7,12-Dimethylbenz [α]anthracene-Induced Mammary Mutagenesis and Carcinogenesis in Ovariectomized Big Blue Transgenic Rats,” Carcinogenesis, Vol. 27, No. 10, 2006, pp. 1970-1979. doi:10.1093/carcin/bgl028

[29]   L. Gu, S. E. House, R. L. Prior, N. Fang, M. J. J. Ronis, T. B. Clarkson, M. E. Wilson and T. M. Badger, ”Metabolic Phenotypes of Isoflavones Differ Among Female Rats, Pigs, Monkeys, and Women,” Journal of Nutrition, Vol. 136, No. 5, 2006, pp. 1215-1221.

[30]   F. Rafii, L. D. Jackson, I. Ross, T. M. Heinze, S. M. Lewis, A. Aidoo, L. Lyn-Cook and M. Manjanatha, “Metabolism of Daidzein by Fecal Bacteria in Rats,” Comparative Medicine, Vol. 57, No. 3, 2007, pp. 282-286.

[31]   K. W?h?l?, A. Salakka and H. Adlercreutz, “Synthesis of Novel Mammalian Metabolites of the Isoflavonoid Phytoestrogens Daidzein and Genistein,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 217, No. 3, 1998, pp. 293-299.

[32]   National Research Council, “Guide For the Care and Use of Laboratory Animals,” National Academies Press, Washington DC, 1996, p. 140.

[33]   National Research Council and Committee on Well-Being of Nonhuman Primates, “Psychological Well-Being of Nonhuman Primates,” National Academies Press, Washington DC, 1998, p. 168.

[34]   J. B. Sutherland, B. M. Bridges, T. M. Heinze, M. R. Adams, P. J. Delio, C. Hotchkiss and F. Rafii, “Comparison of the Effects of Antimicrobial Agents from Three Different Classes on Metabolism of Isoflavonoids by Colonic Microflora Using Etest Strips,” Current Microbiology, Vol. 64, No. 1, 2012, pp. 60-65. doi:10.1007/s00284-011-0020-4

[35]   I. R. Rowland, H. Wiseman, T. A. B. Sanders, H. Adlercreutz and E. A. Bowey, “Interindividual Variation in Metabolism of Soy Isoflavones and Lignans: Influence of Habitual Diet on Equol Production by the Gut Microflora,” Nutrition and Cancer, Vol. 36, No. 1, 2000, pp. 27-32. doi:10.1207/S15327914NC3601_5

[36]   S. Bolca, S. Possemiers, A. Herregat, I. Huybrechts, A. Heyerick, S. De Vriese, M. Verbruggen, M. H. Depypere, D. De Keukeleire, M. Bracke, S. De Henauw, W. Verstaete and T. Van de Wiele, “Microbial and Dietary Factors are Associated with the Equol Producer Phenotype in Healthy Postmenopausal Women,” Journal of Nutrition, Vol. 137, No. 10, 2007, pp. 2242-2246.

[37]   K. M. Heneman, H. C. Chang, R. L. Prior and F. M. Steinberg, “Soy Protein with and without Isoflavones Fails to Substantially Increase Postprandial Antioxidant Capacity,” Journal of Nutritional Biochemistry, Vol. 18, No. 1, 2007, pp. 46-53. doi:10.1016/j.jnutbio.2006.03.001

[38]   K. Fujimoto, M. Tanaka, Y. Hirao, Y. Nagata, M. Mori, N. Miyanaga, H. Akaza and W. J. Kim, “Age-Stratified Serum Levels of Isoflavones and Proportion of Equol Producers in Japanese and Korean Healthy Men,” Prostate Cancer and Prostatic Diseases, Vol. 11, No. 3, 2008, pp. 252-257. doi:10.1038/sj.pcan.4501030