Skip to main content
SpringerLink
Log in

Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers

Phytochemistry Reviews Aims and scope Submit manuscript

Abstract

The bioavailability of soy isoflavones depends on the composition of the microflora for each subject. Bacteria act on different isoflavones with increased or reduced absorption and cause biotransformation of these compounds into metabolites with higher biological activity. S-equol is the most important metabolite and only 25–65 % of the population have the microflora that produces this compound. The presence of equol-producing bacteria in soy product consumers means that the consumption of such products for prolonged periods leads to lower cardiovascular risk, reduced incidence of prostate and breast cancer, and greater relief from symptoms related to the menopause such as hot flushes and osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Akaza H (2012) Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the “second human genome”. Cancer Sci 103:969–975

    PubMed  CAS  Google Scholar 

  • Arora A, Nair MG, Strasburg GM (1998) Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys 356:133–141

    PubMed  CAS  Google Scholar 

  • Arora A, Byrem TM, Nair MG, Strasburg GM (2000) Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys 373:102–109

    PubMed  CAS  Google Scholar 

  • Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Fernandes GR, Tap J, Bruls T, Batto JM, Bertalan M, Borruel N, Casellas F, Fernandez L, Gautier L, Hansen T, Hattori M, Hayashi T, Kleerebezem M, Kurokawa K, Leclerc M, Levenez F, Manichanh C, Nielsen HB, Nielsen T, Pons N, Poulain J, Qin J, Sicheritz-Ponten T, Tims S, Torrents D, Ugarte E, Zoetendal EG, Wang J, Guarner F, Pedersen O, de Vos WM, Brunak S, Dore J, Meta HITC, Antolin M, Artiguenave F, Blottiere HM, Almeida M, Brechot C, Cara C, Chervaux C, Cultrone A, Delorme C, Denariaz G, Dervyn R, Foerstner KU, Friss C, van de Guchte M, Guedon E, Haimet F, Huber W, van Hylckama-Vlieg J, Jamet A, Juste C, Kaci G, Knol J, Lakhdari O, Layec S, Le Roux K, Maguin E, Merieux A, Melo Minardi R, M’Rini C, Muller J, Oozeer R, Parkhill J, Renault P, Rescigno M, Sanchez N, Sunagawa S, Torrejon A, Turner K, Vandemeulebrouck G, Varela E, Winogradsky Y, Zeller G, Weissenbach J, Ehrlich SD, Bork P (2011) Enterotypes of the human gut microbiome. Nature 473:174–180

    PubMed  CAS  Google Scholar 

  • Aso T, Uchiyama S, Matsumura Y, Taguchi M, Nozaki M, Takamatsu K, Ishizuka B, Kubota T, Mizunuma H, Ohta H (2012) A natural S-equol supplement alleviates hot flushes and other menopausal symptoms in equol nonproducing postmenopausal Japanese women. J Womens Health (Larchmt) 21:92–100

    Google Scholar 

  • Atkinson C, Berman S, Humbert O, Lampe JW (2004) In vitro incubation of human feces with daidzein and antibiotics suggests interindividual differences in the bacteria responsible for equol production. J Nutr 134:596–599

    PubMed  CAS  Google Scholar 

  • Atkinson C, Newton KM, Aiello Bowles EJ, Lehman CD, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2009) Daidzein-metabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. Breast Cancer Res Treat 116:587–594

    PubMed  CAS  Google Scholar 

  • Atkinson C, Newton KM, Yong M, Stanczyk FZ, Westerlind KC, Li L, Lampe JW (2012) Daidzein-metabolizing phenotypes in relation to bone density and body composition among premenopausal women in the United States. Metabolism 61:1678–1682

    PubMed  CAS  Google Scholar 

  • Bandara M, Arun SJ, Allanson M, Widyarini S, Chai Z, Reeve VE (2010) Topical isoflavonoids reduce experimental cutaneous inflammation in mice. Immunol Cell Biol 88:727–733

    PubMed  CAS  Google Scholar 

  • Barnes S, Sfakianos J, Coward L, Kirk M (1996) Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues. Adv Exp Med Biol 401:87–100

    PubMed  CAS  Google Scholar 

  • Barnes S, Prasain J, D’Alessandro T, Arabshahi A, Botting N, Lila MA, Jackson G, Janle EM, Weaver CM (2011) The metabolism and analysis of isoflavones and other dietary polyphenols in foods and biological systems. Food Funct 2:235–244

    PubMed  CAS  Google Scholar 

  • Bolca S, Verstraete W (2010) Microbial equol production attenuates colonic methanogenesis and sulphidogenesis in vitro. Anaerobe 16:247–252

    PubMed  CAS  Google Scholar 

  • Bonacasa B, Siow RC, Mann GE (2011) Impact of dietary soy isoflavones in pregnancy on fetal programming of endothelial function in offspring. Microcirculation 18:270–285

    PubMed  CAS  Google Scholar 

  • Bonorden MJ, Greany KA, Wangen KE, Phipps WR, Feirtag J, Adlercreutz H, Kurzer MS (2004) Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women. Eur J Clin Nutr 58:1635–1642

    PubMed  CAS  Google Scholar 

  • Buus NH, Hansson NC, Rodriguez-Rodriguez R, Stankevicius E, Andersen MR, Simonsen U (2011) Antiatherogenic effects of oleanolic acid in apolipoprotein E knockout mice. Eur J Pharmacol 670:519–526

    PubMed  CAS  Google Scholar 

  • Cai Y, Guo K, Chen C, Wang P, Zhang B, Zhou Q, Mei F, Su Y (2012) Soya isoflavone consumption in relation to carotid intima-media thickness in Chinese equol excretors aged 40–65 years. Br J Nutr 108:1698–1704

    PubMed  CAS  Google Scholar 

  • Chassard C, Dapoigny M, Scott KP, Crouzet L, Del’homme C, Marquet P, Martin JC, Pickering G, Ardid D, Eschalier A, Dubray C, Flint HJ, Bernalier-Donadille A (2012) Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther 35:828–838

    PubMed  CAS  Google Scholar 

  • Chen KI, Erh MH, Su NW, Liu WH, Chou CC, Cheng KC (2012) Soyfoods and soybean products: from traditional use to modern applications. Appl Microbiol Biotechnol 96:9–22

    PubMed  CAS  Google Scholar 

  • Cheng K-C, Lin J-T, Wu J-Y, Liu W-H (2010) Isoflavone conversion of black soybean by immobilized Rhizopus spp. Food Biotechnol 24:312–331

    CAS  Google Scholar 

  • Chien HL, Huang HY, Chou CC (2006) Transformation of isoflavone phytoestrogens during the fermentation of soymilk with lactic acid bacteria and bifidobacteria. Food Microbiol 23:772–778

    PubMed  CAS  Google Scholar 

  • Chiou RY, Cheng SL (2001) Isoflavone transformation during soybean koji preparation and subsequent miso fermentation supplemented with ethanol and NaCl. J Agric Food Chem 49:3656–3660

    PubMed  CAS  Google Scholar 

  • Choi EJ (2009a) Chronic equol administration attenuates the antioxidant defense system and causes apoptosis in the mouse brain. Food Chem Toxicol 47:1779–1784

    PubMed  CAS  Google Scholar 

  • Choi EJ (2009b) Evaluation of equol function on anti- or prooxidant status in vivo. J Food Sci 74:H65–H71

    PubMed  CAS  Google Scholar 

  • Chung JE, Kim SY, Jo HH, Hwang SJ, Chae B, Kwon DJ, Lew YO, Lim YT, Kim JH, Kim EJ, Kim JH, Kim MR (2008) Antioxidant effects of equol on bovine aortic endothelial cells. Biochem Biophys Res Commun 375:420–424

    PubMed  CAS  Google Scholar 

  • Clerici C, Setchell KD, Battezzati PM, Pirro M, Giuliano V, Asciutti S, Castellani D, Nardi E, Sabatino G, Orlandi S, Baldoni M, Morelli O, Mannarino E, Morelli A (2007) Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J Nutr 137:2270–2278

    PubMed  CAS  Google Scholar 

  • Crawford SL, Jackson EA, Churchill L, Lampe JW, Leung K, Ockene JK (2013) Impact of dose, frequency of administration, and equol production on efficacy of isoflavones for menopausal hot flashes: a pilot randomized trial. Menopause

  • Crozier A, Jaganath IB, Clifford MN (2009) Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 26:1001–1043

    PubMed  CAS  Google Scholar 

  • Curtis PJ, Potter J, Kroon PA, Wilson P, Dhatariya K, Sampson M, Cassidy A (2013) Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial. Am J Clin Nutr 97:936–942

    PubMed  CAS  Google Scholar 

  • Decroos K, Vanhemmens S, Cattoir S, Boon N, Verstraete W (2005) Isolation and characterisation of an equol-producing mixed microbial culture from a human faecal sample and its activity under gastrointestinal conditions. Arch Microbiol 183:45–55

    PubMed  CAS  Google Scholar 

  • Doerge D, Chang H, Churchwell M, Holder C (2000) Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry. Drug Metab Dispos 3:298–307

    Google Scholar 

  • Dong JY, Qin LQ (2011) Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat 125:315–323

    PubMed  CAS  Google Scholar 

  • Franke AA, Halm BM, Ashburn LA (2008) Isoflavones in children and adults consuming soy. Arch Biochem Biophys 476:161–170

    PubMed  CAS  Google Scholar 

  • Frankenfeld CL (2011) O-desmethylangolensin: the importance of equol’s lesser known cousin to human health. Adv Nutr 2:317–324

    PubMed  CAS  Google Scholar 

  • Frankenfeld CL, McTiernan A, Aiello EJ, Thomas WK, LaCroix K, Schramm J, Schwartz SM, Holt VL, Lampe JW (2004) Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women. Cancer Epidemiol Biomarkers Prev 13:1156–1162

    PubMed  CAS  Google Scholar 

  • Fujimoto K, Tanaka M, Hirao Y, Nagata Y, Mori M, Miyanaga N, Akaza H, Kim WJ (2008) Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men. Prostate Cancer Prostatic Dis 11:252–257

    PubMed  CAS  Google Scholar 

  • Gardana C, Canzi E, Simonetti P (2009) The role of diet in the metabolism of daidzein by human faecal microbiota sampled from Italian volunteers. J Nutr Biochem 20:940–947

    PubMed  CAS  Google Scholar 

  • Gardner CD, Oelrich B, Liu JP, Feldman D, Franke AA, Brooks JD (2009) Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation. Prostate 69:719–726

    PubMed  CAS  Google Scholar 

  • Gold EB, Sternfeld B, Kelsey JL, Brown C, Mouton C, Reame N, Salamone L, Stellato R (2000) Relation of demographic and lifestyle factors to symptoms in a multi-racial/ethnic population of women 40–55 years of age. Am J Epidemiol 152:463–473

    PubMed  CAS  Google Scholar 

  • Guo K, Zhang B, Chen C, Uchiyama S, Ueno T, Chen Y, Su Y (2010) Daidzein-metabolising phenotypes in relation to serum lipids and uric acid in adults in Guangzhou, China. Br J Nutr 104:118–124

    PubMed  CAS  Google Scholar 

  • Hall WL, Vafeiadou K, Hallund J, Bugel S, Reimann M, Koebnick C, Zunft HJ, Ferrari M, Branca F, Dadd T, Talbot D, Powell J, Minihane AM, Cassidy A, Nilsson M, Dahlman-Wright K, Gustafsson JA, Williams CM (2006) Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production. Am J Clin Nutr 83:592–600

    PubMed  CAS  Google Scholar 

  • Hedlund TE, Johannes WU, Miller GJ (2003) Soy isoflavonoid equol modulates the growth of benign and malignant prostatic epithelial cells in vitro. Prostate 54:68–78

    PubMed  Google Scholar 

  • Hirvonen J, Rajalin AM, Wohlfahrt G, Adlercreutz H, Wahala K, Aarnisalo P (2011) Transcriptional activity of estrogen-related receptor gamma (ERRgamma) is stimulated by the phytoestrogen equol. J Steroid Biochem Mol Biol 123:46–57

    PubMed  CAS  Google Scholar 

  • Horii K, Adachi T, Matsuda T, Tanaka T, Sahara H, Shibasaki S, Ogino C, Hata Y, Ueda M, Kondo A (2009) Improvement of isoflavone aglycones production using β-glucosidase secretory produced in recombinant Aspergillus oryzae. J Mol Catal B Enzym 59:297–301

    CAS  Google Scholar 

  • Hozawa A, Sugawara Y, Tomata Y, Kakizaki M, Tsuboya T, Ohmori-Matsuda K, Nakaya N, Kuriyama S, Fukao A, Tsuji I (2013) Relationship Between Serum Isoflavone Levels and Disability-Free Survival Among Community-Dwelling Elderly Individuals: nested Case-Control Study of the Tsurugaya Project. J Gerontol Ser A Biol Sci Med Sci 68:465–472

    CAS  Google Scholar 

  • Hur HG, Lay JO, Beger RD, Freeman JP, Rafii F (2000) Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. Arch Microbiol 174:422–428

    PubMed  CAS  Google Scholar 

  • Hur HG, Beger RD, Heinze TM, Lay JO Jr, Freeman JP, Dore J, Rafii F (2002) Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of the isoflavonoid daidzein. Arch Microbiol 178:8–12

    PubMed  CAS  Google Scholar 

  • Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A (2003) The phytoestrogen equol increases nitric oxide availability by inhibiting superoxide production: an antioxidant mechanism for cell-mediated LDL modification. Free Radic Biol Med 34:1271–1282

    PubMed  CAS  Google Scholar 

  • Ishimi Y (2010) Dietary equol and bone metabolism in postmenopausal Japanese women and osteoporotic mice. J Nutr 140:1373S–1376S

    PubMed  CAS  Google Scholar 

  • Ismail B, Hayes K (2005) Beta-glycosidase activity toward different glycosidic forms of isoflavones. J Agric Food Chem 53:4918–4924

    PubMed  CAS  Google Scholar 

  • Izumi T, Piskula MK, Osawa S, Obata A, Tobe K, Saito M, Kataoka S, Kubota Y, Kikuchi M (2000) Soy isoflavone aglycones are absorbed faster and in higher amounts than their glucosides in humans. J Nutr 130:1695–1699

    PubMed  CAS  Google Scholar 

  • Jackson MD, McFarlane-Anderson ND, Simon GA, Bennett FI, Walker SP (2010) Urinary phytoestrogens and risk of prostate cancer in Jamaican men. Cancer Causes Control 21:2249–2257

    PubMed  Google Scholar 

  • Jackson RL, Greiwe JS, Schwen RJ (2011) Ageing skin: oestrogen receptor beta agonists offer an approach to change the outcome. Exp Dermatol 20:879–882

    PubMed  CAS  Google Scholar 

  • Jenks BH, Iwashita S, Nakagawa Y, Ragland K, Lee J, Carson WH, Ueno T, Uchiyama S (2012) A pilot study on the effects of S-equol compared to soy isoflavones on menopausal hot flash frequency. J Womens Health (Larchmt) 21:674–682

    Google Scholar 

  • Jin JS, Nishihata T, Kakiuchi N, Hattori M (2008) Biotransformation of C-glucosylisoflavone puerarin to estrogenic (3S)-equol in co-culture of two human intestinal bacteria. Biol Pharm Bull 31:1621–1625

    PubMed  CAS  Google Scholar 

  • Jin JS, Kitahara M, Sakamoto M, Hattori M, Benno Y (2010) Slackia equolifaciens sp. nov., a human intestinal bacterium capable of producing equol. Int J Syst Evol Microbiol 60:1721–1724

    PubMed  CAS  Google Scholar 

  • Jou HJ, Wu SC, Chang FW, Ling PY, Chu KS, Wu WH (2008) Effect of intestinal production of equol on menopausal symptoms in women treated with soy isoflavones. Int J Gynaecol Obstet 102:44–49

    PubMed  CAS  Google Scholar 

  • Joy S, Siow RC, Rowlands DJ, Becker M, Wyatt AW, Aaronson PI, Coen CW, Kallo I, Jacob R, Mann GE (2006) The isoflavone Equol mediates rapid vascular relaxation: Ca2+-independent activation of endothelial nitric-oxide synthase/Hsp90 involving ERK1/2 and Akt phosphorylation in human endothelial cells. J Biol Chem 281:27335–27345

    PubMed  CAS  Google Scholar 

  • Kamiyama M, Kishimoto Y, Tani M, Utsunomiya K, Kondo K (2009) Effects of equol on oxidized low-density lipoprotein-induced apoptosis in endothelial cells. J Atheroscler Thromb 16:239–249

    PubMed  CAS  Google Scholar 

  • Kaya M, Ito J, Kotaka A, Matsumura K, Bando H, Sahara H, Ogino C, Shibasaki S, Kuroda K, Ueda M, Kondo A, Hata Y (2008) Isoflavone aglycones production from isoflavone glycosides by display of beta-glucosidase from Aspergillus oryzae on yeast cell surface. Appl Microbiol Biotechnol 79:51–60

    PubMed  CAS  Google Scholar 

  • Kelly GE, Joannou GE, Reeder AY, Nelson C, Waring MA (1995) The variable metabolic response to dietary isoflavones in humans. Proc Soc Exp Biol Med 208:40–43

    PubMed  CAS  Google Scholar 

  • Kolodziejczyk-Czepas J (2012) Trifolium species-derived substances and extracts–biological activity and prospects for medicinal applications. J Ethnopharmacol 143:14–23

    PubMed  Google Scholar 

  • Kreijkamp-Kaspers S, Kok L, Bots ML, Grobbee DE, Lampe JW, van der Schouw YT (2005) Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women. Am J Clin Nutr 81:189–195

    PubMed  CAS  Google Scholar 

  • Landstrom M, Zhang JX, Hallmans G, Aman P, Bergh A, Damber JE, Mazur W, Wahala K, Adlercreutz H (1998) Inhibitory effects of soy and rye diets on the development of Dunning R3327 prostate adenocarcinoma in rats. Prostate 36:151–161

    PubMed  CAS  Google Scholar 

  • Lun-Cheng K, Kung-Ta L (2008) Cloning, expression, and characterization of two β-glucosidases from isoflavone glycoside-hydrolyzing Bacillus subtilis natto. J Agric Food Chem 1:119–125

    Google Scholar 

  • Lund TD, Blake C, Bu L, Hamaker AN, Lephart ED (2011) Equol an isoflavonoid: potential for improved prostate health, in vitro and in vivo evidence. Reprod Biol Endocrinol 9:4

    PubMed  CAS  Google Scholar 

  • Maccaferri S, Biagi E, Brigidi P (2011) Metagenomics: key to human gut microbiota. Dig Dis 29:525–530

    PubMed  Google Scholar 

  • Magee PJ, Raschke M, Steiner C, Duffin JG, Pool-Zobel BL, Jokela T, Wahala K, Rowland IR (2006) Equol: a comparison of the effects of the racemic compound with that of the purified S-enantiomer on the growth, invasion, and DNA integrity of breast and prostate cells in vitro. Nutr Cancer 54:232–242

    PubMed  CAS  Google Scholar 

  • Malaivijitnond S (2012) Medical applications of phytoestrogens from the Thai herb Pueraria mirifica. Front Med 6:8–21

    PubMed  Google Scholar 

  • Malashree L, Mudgil P, Dagar SS, Kumar S, Puniya AK (2012) β-Glucosidase activity of lactobacilli for biotransformation of Soy Isoflavones. Food Biotechnol. (Philadelphia, PA, US) 26: 154–163

  • Marazza JA, Nazareno MA, de Giori GS, Garro MS (2012) Enhancement of the antioxidant capacity of soymilk by fermentation with Lactobacillus rhamnosus. Journal of Functional Foods 4:594–601

    CAS  Google Scholar 

  • Marteau P (2009) Bacterial flora in inflammatory bowel disease. Dig Dis 27(Suppl 1):99–103

    PubMed  Google Scholar 

  • Maruo T, Sakamoto M, Ito C, Toda T, Benno Y (2008) Adlercreutzia equolifaciens gen. nov., sp. nov., an equol-producing bacterium isolated from human faeces, and emended description of the genus Eggerthella. Int J Syst Evol Microbiol 58:1221–1227

    PubMed  CAS  Google Scholar 

  • Mase T, Mori S, Yokoe M (2004) Purification, Characterization, and a Potential Application of β-Glucosidase from Aspergillus pulverulentus YM-80. J Appl Glycosci 211–216

  • Masilamani M, Wei J, Sampson HA (2012) Regulation of the immune response by soybean isoflavones. Immunol Res 54:95–110

    PubMed  CAS  Google Scholar 

  • Matsuura M, Obata A (1993) Beta-glucosidases from soybeans hydrolyze daidzin and genistin. J Food Sci 58:144–147

    CAS  Google Scholar 

  • Matthies A, Blaut M, Braune A (2009) Isolation of a human intestinal bacterium capable of daidzein and genistein conversion. Appl Environ Microbiol 75:1740–1744

    PubMed  CAS  Google Scholar 

  • Meyer BJ, Larkin TA, Owen AJ, Astheimer LB, Tapsell LC, Howe PR (2004) Limited lipid-lowering effects of regular consumption of whole soybean foods. Ann Nutr Metab 48:67–78

    PubMed  CAS  Google Scholar 

  • Miyanaga N, Akaza H, Hinotsu S, Fujioka T, Naito S, Namiki M, Takahashi S, Hirao Y, Horie S, Tsukamoto T, Mori M, Tsuji H (2012) Prostate cancer chemoprevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 103:125–130

    PubMed  CAS  Google Scholar 

  • Morimoto Y, Conroy SM, Pagano IS, Isaki M, Franke AA, Nordt FJ, Maskarinec G (2012) Urinary estrogen metabolites during a randomized soy trial. Nutr Cancer 64:307–314

    PubMed  CAS  Google Scholar 

  • Munoz Y, Garrido A, Valladares L (2009) Equol is more active than soy isoflavone itself to compete for binding to thromboxane A(2) receptor in human platelets. Thromb Res 123:740–744

    PubMed  CAS  Google Scholar 

  • Muthyala RS, Ju YH, Sheng S, Williams LD, Doerge DR, Katzenellenbogen BS, Helferich WG, Katzenellenbogen JA (2004) Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem 12:1559–1567

    PubMed  CAS  Google Scholar 

  • Nagarajan S, Burris RL, Stewart BW, Wilkerson JE, Badger TM (2008) Dietary soy protein isolate ameliorates atherosclerotic lesions in apolipoprotein E-deficient mice potentially by inhibiting monocyte chemoattractant protein-1 expression. J Nutr 138:332–337

    PubMed  CAS  Google Scholar 

  • Nagata C, Ueno T, Uchiyama S, Nagao Y, Yamamoto S, Shibuya C, Kashiki Y, Shimizu H (2008) Dietary and lifestyle correlates of urinary excretion status of equol in Japanese women. Nutr Cancer 60:49–54

    PubMed  CAS  Google Scholar 

  • Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS (2004) Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer. J Nutr 134:1998–2003

    PubMed  CAS  Google Scholar 

  • Ohigashi S, Sudo K, Kobayashi D, Takahashi O, Takahashi T, Asahara T, Nomoto K, Onodera H (2013) Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. Dig Dis Sci

  • Okabe Y, Shimazu T, Tanimoto H (2011) Higher bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans compared with glucoside-rich non-fermented soybeans in Japanese postmenopausal women. J Sci Food Agric 91:658–663

    PubMed  CAS  Google Scholar 

  • Otieno DO, Shah NP (2007) Endogenous beta-glucosidase and beta-galactosidase activities from selected probiotic micro-organisms and their role in isoflavone biotransformation in soymilk. J Appl Microbiol 103:910–917

    PubMed  CAS  Google Scholar 

  • Park SY, Wilkens LR, Franke AA, Le Marchand L, Kakazu KK, Goodman MT, Murphy SP, Henderson BE, Kolonel LN (2009) Urinary phytoestrogen excretion and prostate cancer risk: a nested case-control study in the Multiethnic Cohort. Br J Cancer 101:185–191

    PubMed  CAS  Google Scholar 

  • Park HY, Kim M, Han J (2011) Stereospecific microbial production of isoflavanones from isoflavones and isoflavone glucosides. Appl Microbiol Biotechnol 91:1173–1181

    PubMed  CAS  Google Scholar 

  • Parkar SG, Stevenson DE, Skinner MA (2008) The potential influence of fruit polyphenols on colonic microflora and human gut health. Int J Food Microbiol 124:295–298

    PubMed  CAS  Google Scholar 

  • Peñalvo JL, Nurmi T, Adlercreutz H (2004) A simplified HPLC method for total isoflavones in soy products. Food Chem 87:297–305

    Google Scholar 

  • Pereboom D, Gilaberte Y, Sinues B, Escanero J, Alda JO (1999) Antioxidant intracellular activity of genistein and equol. J Med Food 2:253–256

    PubMed  CAS  Google Scholar 

  • Pham TT, Shah NP (2007) Biotransformation of isoflavone glycosides by Bifidobacterium animalis in soymilk supplemented with skim milk powder. J Food Sci 72:M316–M324

    PubMed  CAS  Google Scholar 

  • Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490:55–60

    PubMed  CAS  Google Scholar 

  • Raimondi S, Roncaglia L, De Lucia M, Amaretti A, Leonardi A, Pagnoni UM, Rossi M (2009) Bioconversion of soy isoflavones daidzin and daidzein by Bifidobacterium strains. Appl Microbiol Biotechnol 81:943–950

    PubMed  CAS  Google Scholar 

  • Reeve VE, Widyarini S, Domanski D, Chew E, Barnes K (2005) Protection against photoaging in the hairless mouse by the isoflavone equol. Photochem Photobiol 81:1548–1553

    PubMed  CAS  Google Scholar 

  • Rekha CR, Vijayalakshmi G (2011) Isoflavone phytoestrogens in soymilk fermented with beta-glucosidase producing probiotic lactic acid bacteria. Int J Food Sci Nutr 62:111–120

    PubMed  CAS  Google Scholar 

  • Ringel-Kulka T, Cheng J, Ringel Y, Salojarvi J, Carroll I, Palva A, de Vos WM, Satokari R (2013) Intestinal microbiota in healthy U.S. Young children and adults-a high throughput microarray analysis. PLoS ONE 8:e64315

    PubMed  CAS  Google Scholar 

  • Rowland IR, Wiseman H, Sanders TA, Adlercreutz H, Bowey EA (2000) Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora. Nutr Cancer 36:27–32

    PubMed  CAS  Google Scholar 

  • Schoefer L, Mohan R, Braune A, Birringer M, Blaut M (2002) Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus. FEMS Microbiol Lett 208:197–202

    PubMed  CAS  Google Scholar 

  • Schwen RJ, Nguyen L, Jackson RL (2012) Elucidation of the metabolic pathway of S-equol in rat, monkey and man. Food Chem Toxicol 50:2074–2083

    PubMed  CAS  Google Scholar 

  • Setchell KDR, Clerici C (2010) Equol: history, chemistry, and formation. J Nutr 140:1355s–1362s

    PubMed  CAS  Google Scholar 

  • Setchell KDR, Brown NM, Lydeking-Olsen E (2002a) The clinical importance of the metabolite equol—a clue to the effectiveness of soy and its isoflavones. J Nutr 132:3577–3584

    PubMed  CAS  Google Scholar 

  • Setchell KDR, Brown NM, Zimmer-Nechemias L, Brashear WT, Wolfe BE, Kirschner AS, Heubi JE (2002b) Evidence for lack of absorption of soy isoflavone glycosides in humans, supporting the crucial role of intestinal metabolism for bioavailability. Am J Clin Nutr 76:447–453

    PubMed  CAS  Google Scholar 

  • Sierens J, Hartley JA, Campbell MJ, Leathem AJ, Woodside JV (2001) Effect of phytoestrogen and antioxidant supplementation on oxidative DNA damage assessed using the comet assay. Mutat Res 485:169–176

    PubMed  CAS  Google Scholar 

  • Sierens J, Hartley JA, Campbell MJ, Leathem AJ, Woodside JV (2002) In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen 22:227–234

    PubMed  CAS  Google Scholar 

  • Sjoberg V, Sandstrom O, Hedberg M, Hammarstrom S, Hernell O, Hammarstrom ML (2013) Intestinal T-cell responses in celiac disease: impact of celiac disease associated bacteria. PLoS ONE 8:e53414

    PubMed  Google Scholar 

  • Smith B, Bode S, Skov TH, Mirsepasi H, Greisen G, Krogfelt KA (2012) Investigation of the early intestinal microflora in premature infants with/without necrotizing enterocolitis using two different methods. Pediatr Res 71:115–120

    PubMed  CAS  Google Scholar 

  • Sugiyama Y, Masumori N, Fukuta F, Yoneta A, Hida T, Yamashita T, Minatoya M, Nagata Y, Mori M, Tsuji H, Akaza H, Tsukamoto T (2013) Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk. Asian Pac J Cancer Prev 14:1–4

    PubMed  Google Scholar 

  • Sutherland JB, Bridges BM, Heinze TM, Adams MR, Delio PJ, Hotchkiss C, Rafii F (2012) Comparison of the effects of antimicrobial agents from three different classes on metabolism of isoflavonoids by colonic microflora using Etest strips. Curr Microbiol 64:60–65

    PubMed  CAS  Google Scholar 

  • Takahashi Y, Lavigne JA, Hursting SD, Chandramouli GV, Perkins SN, Kim YS, Wang TT (2006) Molecular signatures of soy-derived phytochemicals in androgen-responsive prostate cancer cells: a comparison study using DNA microarray. Mol Carcinog 45:943–956

    PubMed  CAS  Google Scholar 

  • Tamura M, Tsushida T, Shinohara K (2007) Isolation of an isoflavone-metabolizing, Clostridium-like bacterium, strain TM-40, from human faeces. Anaerobe 13:32–35

    PubMed  CAS  Google Scholar 

  • Tamura M, Hori S, Nakagawa H (2011) Lactobacillus rhamnosus JCM 2771: impact on metabolism of isoflavonoids in the fecal flora from a male equol producer. Curr Microbiol 62:1632–1637

    PubMed  CAS  Google Scholar 

  • Tanaka M, Fujimoto K, Chihara Y, Torimoto K, Yoneda T, Tanaka N, Hirayama A, Miyanaga N, Akaza H, Hirao Y (2009) Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis 12:247–252

    PubMed  CAS  Google Scholar 

  • Tonetti DA, Zhang Y, Zhao H, Lim SB, Constantinou AI (2007) The effect of the phytoestrogens genistein, daidzein, and equol on the growth of tamoxifen-resistant T47D/PKC alpha. Nutr Cancer 58:222–229

    PubMed  CAS  Google Scholar 

  • Tousen Y, Ezaki J, Fujii Y, Ueno T, Nishimuta M, Ishimi Y (2011) Natural S-equol decreases bone resorption in postmenopausal, non-equol-producing Japanese women: a pilot randomized, placebo-controlled trial. Menopause 18:563–574

    PubMed  Google Scholar 

  • Travis RC, Spencer EA, Allen NE, Appleby PN, Roddam AW, Overvad K, Johnsen NF, Olsen A, Kaaks R, Linseisen J, Boeing H, Nothlings U, Bueno-de-Mesquita HB, Ros MM, Sacerdote C, Palli D, Tumino R, Berrino F, Trichopoulou A, Dilis V, Trichopoulos D, Chirlaque MD, Ardanaz E, Larranaga N, Gonzalez C, Suarez LR, Sanchez MJ, Bingham S, Khaw KT, Hallmans G, Stattin P, Rinaldi S, Slimani N, Jenab M, Riboli E, Key TJ (2009) Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition. Br J Cancer 100:1817–1823

    PubMed  CAS  Google Scholar 

  • Tsangalis D, Ashton JF, McGill AEJ, Shah NP (2002) Enzymic transformation of isoflavone phytoestrogens in soymilk by beta-glucosidase-producing bifidobacteria. J Food Sci 67:3104–3113

    CAS  Google Scholar 

  • Tsangalis D, Wilcox G, Shah NP, Stojanovska L (2005) Bioavailability of isoflavone phytoestrogens in postmenopausal women consuming soya milk fermented with probiotic bifidobacteria. Br J Nutr 93:867–877

    PubMed  CAS  Google Scholar 

  • Tsuchihashi R, Sakamoto S, Kodera M, Nohara T, Kinjo J (2008) Microbial metabolism of soy isoflavones by human intestinal bacterial strains. J Nat Med 62:456–460

    PubMed  CAS  Google Scholar 

  • Tsuji H, Moriyama K, Nomoto K, Miyanaga N, Akaza H (2010) Isolation and characterization of the equol-producing bacterium Slackia sp. strain NATTS. Arch Microbiol 192:279–287

    PubMed  CAS  Google Scholar 

  • Turner NJ, Thomson BM, Shaw IC (2003) Bioactive isoflavones in functional foods: the importance of gut microflora on bioavailability. Nutr Rev 61:204–213

    PubMed  Google Scholar 

  • Turner R, Baron T, Wolffram S, Minihane AM, Cassidy A, Rimbach G, Weinberg PD (2004) Effect of circulating forms of soy isoflavones on the oxidation of low density lipoprotein. Free Radic Res 38:209–216

    PubMed  CAS  Google Scholar 

  • Uchiyama S, Ueno T, Imaizumi K, Kumemura M, Masaki K, Shimizu S (1999) Isoflavone-containing health food and pharmaceuticals. Otsuka Pharmaceutical Co., Ltd., Japan, p 49

  • Uchiyama S, Ueno T, Suzuki T (2005) Composition containing lactic acid bacterium producing equol. Otsuka Pharmaceutical Co., Ltd., Japan, p 47

  • Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N (2013) Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol (Oxf) 78:365–372

    CAS  Google Scholar 

  • Venkitaraman R, Thomas K, Grace P, Dearnaley D, Horwich A, Huddart R, Parker CC (2008) Baseline urinary phytoestrogen levels and the natural history of untreated, localised prostate cancer in a British population. Int J Biol Markers 23:192–197

    PubMed  CAS  Google Scholar 

  • Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE, van der Schouw YT (2008) Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17:2632–2638

    PubMed  CAS  Google Scholar 

  • Vitale DC, Piazza C, Melilli B, Drago F, Salomone S (2012) Isoflavones: estrogenic activity, biological effect and bioavailability. Eur J Drug Metab Pharmacokinet

  • Walker AW, Sanderson JD, Churcher C, Parkes GC, Hudspith BN, Rayment N, Brostoff J, Parkhill J, Dougan G, Petrovska L (2011) High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 11:7

    PubMed  Google Scholar 

  • Wang XL, Hur HG, Lee JH, Kim KT, Kim SI (2005) Enantioselective synthesis of S-equol from dihydrodaidzein by a newly isolated anaerobic human intestinal bacterium. Appl Environ Microbiol 71:214–219

    PubMed  CAS  Google Scholar 

  • Ward H, Chapelais G, Kuhnle GG, Luben R, Khaw KT, Bingham S (2008a) Lack of prospective associations between plasma and urinary phytoestrogens and risk of prostate or colorectal cancer in the European Prospective into Cancer-Norfolk study. Cancer Epidemiol Biomarkers Prev 17:2891–2894

    PubMed  CAS  Google Scholar 

  • Ward H, Chapelais G, Kuhnle GG, Luben R, Khaw KT, Bingham S, European Prospective into Cancer-Norfolk c (2008b) Breast cancer risk in relation to urinary and serum biomarkers of phytoestrogen exposure in the European Prospective into Cancer-Norfolk cohort study. Breast Cancer Res 10:R32

    PubMed  Google Scholar 

  • Wei QK, Chen TR, Chen JT (2007) Using of Lactobacillus and Bifidobacterium to product the isoflavone aglycones in fermented soymilk. Int J Food Microbiol 117:120–124

    PubMed  CAS  Google Scholar 

  • Widyarini S, Husband AJ, Reeve VE (2005) Protective effect of the isoflavonoid equol against hairless mouse skin carcinogenesis induced by UV radiation alone or with a chemical cocarcinogen. Photochem Photobiol 81:32–37

    PubMed  CAS  Google Scholar 

  • Wong JM, Kendall CW, Marchie A, Liu Z, Vidgen E, Holmes C, Jackson CJ, Josse RG, Pencharz PB, Rao AV, Vuksan V, Singer W, Jenkins DJ (2012) Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods. Am J Clin Nutr 95:564–571

    PubMed  CAS  Google Scholar 

  • Wu J, Oka J, Higuchi M, Tabata I, Toda T, Fujioka M, Fuku N, Teramoto T, Okuhira T, Ueno T, Uchiyama S, Urata K, Yamada K, Ishimi Y (2006) Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial. Metabolism 55:423–433

    PubMed  CAS  Google Scholar 

  • Wu AH, Yu MC, Tseng CC, Pike MC (2008) Epidemiology of soy exposures and breast cancer risk. Br J Cancer 98:9–14

    PubMed  CAS  Google Scholar 

  • Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108

    PubMed  CAS  Google Scholar 

  • Wu X, Cai H, Gao YT, Dai Q, Li H, Cai Q, Yang G, Franke AA, Zheng W, Shu XO (2012) Correlations of urinary phytoestrogen excretion with lifestyle factors and dietary intakes among middle-aged and elderly Chinese women. Int J Mol Epidemiol Genet 3:18–29

    PubMed  CAS  Google Scholar 

  • Yokoyama S, Suzuki T (2008) Isolation and characterization of a novel equol-producing bacterium from human feces. Biosci Biotechnol Biochem 72:2660–2666

    PubMed  CAS  Google Scholar 

  • Yokoyama S, Niwa T, Osawa T, Suzuki T (2010) Characterization of an O-desmethylangolensin-producing bacterium isolated from human feces. Arch Microbiol 192:15–22

    PubMed  CAS  Google Scholar 

  • Yoneda T, Ueno T, Uchiyama S (2011) S-equol and the fermented soy product SE5-OH containing S-equol similarly decrease ovariectomy-induced increase in rat tail skin temperature in an animal model of hot flushes. Menopause 18:814–820

    PubMed  Google Scholar 

  • Youn SY (2012) Identification of the β-Glucosidase Gene from Bifidobacterium animalis subsp. lactis and Its Expression in B. bifidum BGN4. J Microbiol Biotechnol 22:1714–1723

    PubMed  CAS  Google Scholar 

  • Young ND, Bharti AK (2012) Genome-enabled insights into legume biology. Annu Rev Plant Biol 63:283–305

    PubMed  CAS  Google Scholar 

  • Yuan JP, Wang JH, Liu X (2007) Metabolism of dietary soy isoflavones to equol by human intestinal microflora–implications for health. Mol Nutr Food Res 51:765–781

    PubMed  CAS  Google Scholar 

  • Zhang Y, Hendrich S, Murphy P (2003) Glucuronides are the main isoflavone metabolites in women. J Nutr 133:399–404

    PubMed  CAS  Google Scholar 

  • Zheng W, Zhang Y, Ma D, Shi Y, Liu C, Wang P (2012) (±)Equol inhibits invasion in prostate cancer DU145 cells possibly via down-regulation of matrix metalloproteinase-9, matrix metalloproteinase-2 and urokinase-type plasminogen activator by antioxidant activity. J Clin Biochem Nutr 51:61–67

    PubMed  CAS  Google Scholar 

  • Zhong X, Zhang C (2012) Soy food intake and breast cancer risk: a meta-analysis. Wei Sheng Yan Jiu 41:670–676

    PubMed  Google Scholar 

  • Zhu B, Wang X, Li L (2010) Human gut microbiome: the second genome of human body. Protein Cell 1:718–725

    PubMed  Google Scholar 

  • Zupancic ML, Cantarel BL, Liu Z, Drabek EF, Ryan KA, Cirimotich S, Jones C, Knight R, Walters WA, Knights D, Mongodin EF, Horenstein RB, Mitchell BD, Steinle N, Snitker S, Shuldiner AR, Fraser CM (2012) Analysis of the gut microbiota in the old order Amish and its relation to the metabolic syndrome. PLoS ONE 7:e43052

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work described in this paper was supported by the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (Project P10-AGR5822) and the Ministerio de Ciencia e Innovación, Spain (Project No AGL2009-08864/AGR).

Author information

Authors and Affiliations

  1. Unidad de Gestión Clínica de Microbiología, Hospital Universitario Puerta del Mar, Avenida Ana de Viya, 21, 11009, Cádiz, Spain

    Juan Manuel Sánchez-Calvo & Manuel Antonio Rodríguez-Iglesias

  2. Grupo de Alelopatía, Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biomoléculas (INBIO), Universidad de Cádiz, Campus de Excelencia Internacional Agroalimentario (ceiA3), C/República Saharaui, s/n, 11510, Puerto Real, Cádiz, Spain

    José M. G. Molinillo & Francisco A. Macías

Authors
  1. Juan Manuel Sánchez-Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel Antonio Rodríguez-Iglesias
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José M. G. Molinillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco A. Macías
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco A. Macías.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sánchez-Calvo, J.M., Rodríguez-Iglesias, M.A., Molinillo, J.M.G. et al. Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers. Phytochem Rev 12, 979–1000 (2013). https://doi.org/10.1007/s11101-013-9329-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11101-013-9329-x

Keywords

search

Navigation