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Epidemiology

Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein

Abstract

Background/objectives:

Studies have observed associations between the gut microbiome and obesity. O-desmethylangolensin (ODMA) and equol are gut bacterial metabolites of daidzein, a compound found in high amounts in soy foods. Approximately 80–95% and 25–60% of individuals harbor gut microbial communities capable of producing ODMA or equol, respectively. Given that other phenotypes of gut bacterial metabolism of dietary compounds have been associated with obesity, we hypothesized that daidzein-metabolizing phenotypes would be associated with obesity. The objective of this study was to compare the prevalence of ODMA-producer and equol-producer phenotypes in obese, overweight and normal-weight individuals.

Subjects/methods:

Adults aged 18–95 years (n=297) provided a first-void urine sample after a 3-day soy challenge, and urinary ODMA and equol concentrations were used to classify individuals as producers or non-producers. Body mass index was calculated from self-reported weight and height.

Results:

There were 60 ODMA non-producers and 173 equol non-producers. Obese individuals were 2.8 times more likely to be ODMA non-producers (odds ratio (OR)=2.8, 95% confidence interval (CI): 1.2, 6.2) compared with normal-weight individuals, when adjusted for age, race (white vs non-white), and gender and menopausal status (male, premenopausal female and postmenopausal female). Obesity was not associated with equol-producer phenotype (OR=1.1, 95% CI: 0.5, 2.2). Stronger associations with obesity were observed in the ODMA non-producers who were also equol producers than in the equol non-producers.

Conclusions:

Results from this analysis suggest that the ODMA-producer phenotype, but not equol-producer phenotype, is associated with obesity in adults. These results support further work to replicate these findings and evaluate the mechanisms of the observed associations.

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References

  1. Berg RD . The indigenous gastrointestinal microflora. Trends Microbiol 1996; 4: 430–435.

    Article  CAS  Google Scholar 

  2. Hullar MA, Lampe JW . The gut microbiome and obesity. Nestle Nutr Workshop Ser 2012; 73: 67–79.

    Article  Google Scholar 

  3. Nakamura Y, Tsuji S, Tonogai Y . Determination of the levels of isoflavonoids in soybeans and soy-derived foods and estimation of isoflavonoids in the Japanese daily intake. J AOAC Int 2000; 83: 635–650.

    CAS  PubMed  Google Scholar 

  4. Setchell KD, Clerici C . Equol: pharmacokinetics and biological actions. J Nutr 2010; 140: 1363S–1368S.

    Article  CAS  Google Scholar 

  5. Frankenfeld CL . O-desmethylangolensin: the importance of equol's lesser known cousin to human health. Adv Nutr 2011; 2: 317–324.

    Article  CAS  Google Scholar 

  6. Heinonen S, Wähälä K, Adlercreutz H . Identification of isoflavone metabolites dihydrodaidzein, dihydrogenistein, 6'-OH-O-dma, and cis-4-OH-equol in human urine by gas chromatography-mass spectroscopy using authentic reference compounds. Anal Biochem 1999; 274: 211–219.

    Article  CAS  Google Scholar 

  7. Atkinson C, Frankenfeld CL, Lampe JW . Gut bacterial metabolism of the soy isoflavone daidzein: exploring the relevance to human health. Exp Biol Med (Maywood) 2005; 230: 155–170.

    Article  CAS  Google Scholar 

  8. Setchell KD, Clerici C . Equol: history, chemistry, and formation. J Nutr 2010; 140: 1355S–1362S.

    Article  CAS  Google Scholar 

  9. Frankenfeld CL, Atkinson C, Thomas WK, Gonzalez A, Jokela T, Wähälä K et al. High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart. Br J Nutr 2005; 94: 873–876.

    Article  CAS  Google Scholar 

  10. Song KB, Atkinson C, Frankenfeld CL, Jokela T, Wähälä K, Thomas WK et al. Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls. J Nutr 2006; 136: 1347–1351.

    Article  CAS  Google Scholar 

  11. Lampe JW . Is equol the key to the efficacy of soy foods? Am J Clin Nutr 2009; 89: 1664S–1667S.

    Article  CAS  Google Scholar 

  12. Shor D, Sathyapalan T, Atkin S, Thatcher N . Does equol production determine soy endocrine effects? Eur J Nutr 2012; 51: 389–398.

    Article  CAS  Google Scholar 

  13. Frankenfeld CL . Relationship of obesity and high urinary enterolignan concentrations in 6806 children and adults: analysis of National Health and Nutrition Examination Survey data. Eur J Clin Nutr 2013; 67: 887–889.

    Article  CAS  Google Scholar 

  14. Frankenfeld CL, Atkinson C, Thomas WK, Goode EL, Gonzalez A, Jokela T et al. Familial correlations, segregation analysis, and nongenetic correlates of soy isoflavone-metabolizing phenotypes. Exp Biol Med (Maywood) 2004; 229: 902–913.

    Article  CAS  Google Scholar 

  15. Frankenfeld CL, McTiernan A, Tworoger SS, Atkinson C, Thomas WK, Stanczyk FZ et al. Serum steroid hormones, sex hormone-binding globulin concentrations, and urinary hydroxylated estrogen metabolites in post-menopausal women in relation to daidzein-metabolizing phenotypes. J Steroid Biochem Mol Biol 2004; 88: 399–408.

    Article  CAS  Google Scholar 

  16. World Health Organization (WHO) World Health Organization (WHO) Obesity and overweight. Fact Sheet No. 311. 2012.

  17. Ley RE . Obesity and the human microbiome. Curr Opin Gastroenterol 2010; 26: 5–11.

    Article  Google Scholar 

  18. Finegold SM, Attebery HR, Sutter VL . Effect of diet on human fecal flora: comparison of Japanese and American diets. Am J Clin Nutr 1974; 27: 1456–1469.

    Article  CAS  Google Scholar 

  19. Benno Y, Endo K, Mizutani T, Namba Y, Komori T, Mitsuoka T . Comparison of fecal microflora of elderly persons in rural and urban areas of Japan. Appl Environ Microbiol 1989; 55: 1100–1105.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Mueller S, Saunier K, Hanisch C, Norin E, Alm L, Midtvedt T et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl Environ Microbiol 2006; 72: 1027–1033.

    Article  CAS  Google Scholar 

  21. Zhao L, Xu W, Ibrahim SA, Jin J, Feng J, Jiang J et al. Effects of age and region on fecal microflora in elderly subjects living in Bama, Guangxi, China. Curr Microbiol 2011; 62: 64–70.

    Article  CAS  Google Scholar 

  22. Frankenfeld CL, McTiernan A, Aiello EJ, Thomas WK, LaCroix K, Schramm J et al. Mammographic density in relation to daidzein-metabolizing phenotypes in overweight, postmenopausal women. Cancer Epidemiol Biomarkers Prev 2004; 13: 1156–1162.

    CAS  PubMed  Google Scholar 

  23. Frankenfeld CL, McTiernan A, Thomas WK, LaCroix K, McVarish L, Holt VL et al. Postmenopausal bone mineral densityin relation to soy isoflavone-metabolizing phenotypes. Maturitas 2006; 53: 315–324.

    Article  CAS  Google Scholar 

  24. Atkinson C, Newton KM, Aiello Bowles EJ, Lehman CD, Stanczyk FZ, Westerlind KC et al. Daidzein-metabolizing phenotypes in relation to mammographic breast density among premenopausal women in the United States. Breast Cancer Res Treat 2009; 116: 587–594.

    Article  CAS  Google Scholar 

  25. Atkinson C, Newton KM, Stanczyk FZ, Westerlind KC, Li L, Lampe JW . Daidzein-metabolizing phenotypes in relation to serum hormones and sex hormone binding globulin, and urinary estrogen metabolites in premenopausal women in the United States. Cancer Causes Control 2008; 19: 1085–1093.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  27. Bolca S, Van de Wiele T, Possemiers S . Gut metabotypes govern health effects of dietary polyphenols. Curr Opin Biotechnol 2012; 24: 220–225.

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  30. Schneider H, Blaut M . Anaerobic degradation of flavonoids by Eubacterium ramulus. Arch Microbiol 2000; 173: 71–75.

    Article  CAS  Google Scholar 

  31. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE et al. A core gut microbiome in obese and lean twins. Nature 2009; 457: 480–484.

    Article  CAS  Google Scholar 

  32. Gil-Izquierdo A, Penalvo JL, Gil JI, Medina S, Horcajada MN, Lafay S et al. Soy isoflavones and cardiovascular disease epidemiological, clinical and -omics perspectives. Curr Pharm Biotechnol 2012; 13: 624–631.

    Article  CAS  Google Scholar 

  33. Ishimi Y . Soybean isoflavones in bone health. Forum Nutr 2009; 61: 104–116.

    Article  CAS  Google Scholar 

  34. Jackman KA, Woodman OL, Sobey CG . Isoflavones equol and cardiovascular disease: pharmacological and therapeutic insights. Curr Med Chem 2007; 14: 2824–2830.

    Article  CAS  Google Scholar 

  35. Jackson RL, Greiwe JS, Schwen RJ . Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist. Nutr Rev 2011; 69: 432–448.

    Article  Google Scholar 

  36. Martin D, Song J, Mark C, Eyster K . Understanding the cardiovascular actions of soy isoflavones: potential novel targets for antihypertensive drug development. Cardiovasc Hematol Disorders Drug Targets 2008; 8: 297–312.

    Article  CAS  Google Scholar 

  37. Wiseman H . The therapeutic potential of phytoestrogens. Exp Opin Invest Drugs 2000; 9: 1829–1840.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. Lampe JW . Emerging research on equol and cancer. J Nutr 2010; 140: 1369S–1372S.

    Article  CAS  Google Scholar 

  41. Takeuchi S, Takahashi T, Sawada Y, Iida M, Matsuda T, Kojima H . Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using Chinese hamster ovary cells. Biol Pharm Bull 2009; 32: 195–202.

    Article  CAS  Google Scholar 

  42. Pfitscher A, Reiter E, Jungbauer A . Receptor binding and transactivation activities of red clover isoflavones and their metabolites. J Steroid Biochem Mol Biol 2008; 112: 87–94.

    Article  CAS  Google Scholar 

  43. Lourdes M, Cruz A, Wong WW, Mimouni F, Hachey DL, Setchell KDR et al. Effects of infant nutrition on cholesterol synthesis rates. Pediatr Res 1994; 35: 135–140.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Institutes of Health Grants R03CA089785 and T32CA009168 (CLF). The work was carried out partially within the EU project PHYTOHEALTH QLRT-2001-02453.

DISCLAIMER

This study does not necessarily reflect the views of the commission and in no way anticipates the commission's future policy in this area.

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Correspondence to C L Frankenfeld.

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The authors declare no conflict of interest.

Additional information

Contributors: CLF, CA, KW and JWL contributed to the data acquisition. CLF drafted the article. All authors contributed to the concept and design, interpretation of data and revision of the article for important intellectual content, and approved the final version to be published.

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Frankenfeld, C., Atkinson, C., Wähälä, K. et al. Obesity prevalence in relation to gut microbial environments capable of producing equol or O-desmethylangolensin from the isoflavone daidzein. Eur J Clin Nutr 68, 526–530 (2014). https://doi.org/10.1038/ejcn.2014.23

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