Endocrine Disruptors, Phytoestrogens and Breast Cancer: Comparison
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Please note this is a comparison between Version 2 by Peter Tang and Version 1 by Stefano Magno.
An Endocrine Disruptor (ED) is defined by the U.S. Environmental Protection Agency (EPA) as "an exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction, and developmental process". Both estrogens and EDs, binding to estrogen receptors, elicit downstream gene activation and trigger intracellular signalling cascades in a variety of tissues, thus affecting reproductive health and hormonal dependent cancers risk. Endocrine disruptors are a group of highly heterogeneous molecules, grossly divided into synthetic and natural compounds (phytoestrogens).
  • microbiome
  • endocrine disruptors
  • estrobolome

1. Synthetic Endocrine Disruptors

The synthetic chemicals with endocrine activities have multiple uses, such as industrial solvents/lubricants (polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs)), plastics (bisphenol A (BPA)), plasticizers (phthalates), pesticides (methoxychlor, chlorpyrifos, dichlorodiphenyltrichloroethane (DDT)), fungicides (vinclozolin), pharmaceutical agents (diethylstilbestrol (DES)) and heavy metals such as cadmium [25,26][1][2].
The most common pathways of exposure to EDs are by inhalation, food intake, transplacental and skin contact [25,27,28][1][3][4]. By these means, EDs enter the food chain and accumulate in animal tissues up to humans mainly in adipose tissue, since most of EDs are highly lipophilic [29,30,31][5][6][7].
The mechanisms of action of EDs include a variety of possible pathways involved in endocrine and reproductive systems: via nuclear receptors, nonnuclear steroid hormone receptors (e.g., membrane estrogen receptors (ERs)), nonsteroid receptors (e.g., neurotransmitter receptors such as serotonin, dopamine, norepinephrine), orphan receptors [e.g., aryl hydrocarbon receptor (AhR)], enzymatic pathways involved in steroid biosynthesis and/or metabolism [25][1].
Another mechanism is the aromatase up-regulation (e.g., phenolic EDs) and increased estradiol biosynthesis, which is linked to ER-positive breast cancer cell proliferation in vitro [32][8].
Furthermore, an epigenetic action, such as DNA methylation and/or acetylation and histone modifications, may be involved in mechanisms related to endocrine disruption [33,34,35][9][10][11].
The exposure to EDs has been related to multiple diseases, such as diabetes, metabolic syndrome, obesity, cardiovascular and neurological disorders [29,30,31,32,33,34,35,36,37][5][6][7][8][9][10][11][12][13]. Some EDs such as bisphenol A (BPA), dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) are also associated with infertility and cancer [29,30,31,32,33,34,35,36,37,38,39,40][5][6][7][8][9][10][11][12][13][14][15][16].
According to the International Agency for Research on Cancer (IARC) classification, some of the EDs (BPA, DDT and PCBs) have key characteristics of human carcinogens, since they can alter cell proliferation, cell death or nutrient supply; are genotoxic; have immunosuppressive activity; induce epigenetic alterations, oxidative stress and chronic inflammation [39][15]. In addition, BPA by interacting with the estrogen receptor-α (ERα), induces cell proliferation and reduces apoptosis rate, affecting the prognosis of BC patients [40,41,42][16][17][18].
A growing number of studies have investigated the correlations between EDs and BC onset and progression [43][19]. Breast tissue is particularly susceptible to carcinogenic effects during the third trimester of the first pregnancy, and prolonged exposure to low levels of EDs [44,45,46][20][21][22] can raise the risk of developing cancer in the following years [47,48][23][24].
Some pesticides, including DDT, dichloro-diphenyl-dichloroethylene (DDE), aldrin, and lindane, have been linked in pre- and post-menopausal women to a higher risk of BC [49[25][26],50], either estrogen receptor-positive (-hexachlorocyclohexane and Pentachlorothioanisole) [51][27] or HER2-positive tumors (DDT) [52,53,54][28][29][30]. Among the heavy metals, cadmium was positively associated with BC [55,56][31][32].
Interestingly, women with an altered body composition and an excess of fat mass have shown a greater likelihood of BC after exposure to PCB [57][33], due to the lipophilic nature of these molecules.
Some EDs, such as Bisphenol S (BPS), are also involved in enhancing the progression and the metastatic spread of BC cells, by inducing tumor proliferation and epithelial-mesenchymal transition [58,59][34][35]. The Interplay between endocrine disruptors and microbiota with potential drivers of BC are summarized in Table 1.
Table 1.
Interplay between endocrine disruptors and microbiota with potential drivers of breast cancer.

Source

Molecules

Microrganisms

Outcome

References

Foods

Lignans

Isoflavones

C. methoxybenzovorans

B. pseudocatenulatum WC 401

Firmicutes

Bacteroidetes

F. prausnitzii

Lactobacillus

Enterococcus

Estrogen

Bioavailability

[60,61,62,63,64][36][37][38][39][40]

Plastics

BPA

BPS

Helicobacteraceae

Firmicutes

Clostridia

Lipogenesis

Gluconeogenesis

Tumor proliferation

Metastatic spread

[58,59,65,66][34][35][41][42]

Pesticides

Organophosphates

DDT

DDE

PCB

Bacteroides,

Burkholderiales

Clostridiaceae

Erysiopelotrichaceae

Coprobacillus

Lachnospiraceae

Staphylococcaceae

Gluconeogenesis

Oxidative stress

Changes in insulin

and ghrelin secretion

[49,[50,2565,66

In epidemiological studies, Asian populations who consume on average much more soy products than Western populations, have lower rates of hormone-dependent breast and endometrial cancers [71][47] and a lower incidence of menopausal symptoms and osteoporosis. Soy is the main dietary source of isoflavones. Isoflavones have a chemical structure similar to the human hormone oestrogen. However, they bind to the body’s oestrogen receptors differently, and function differently. Activation of some receptors seems to promote cell growth, but isoflavones more often bind to oestrogen receptors with other effects, potentially acting as a tumour suppressor [71][47].
Different kinds of oestrogen receptors are present in different parts of the body. Activation of some receptors seems to promote cell growth. But studies suggest that isoflavones more often bind to oestrogen receptors with other effects, potentially acting as a tumour suppressor. Nevertheless, in Asian immigrants living in Western nations, whose diet includes more proteins and lipids and less fibers and soy, the risks for hormone-dependent cancers reach the same levels as the western population [72][48].
The main groups of phytoestrogens are lignans, coumestans, stilbenes and isoflavones.
Lignans, as components of plant cell walls, are found in many fiber-rich foods such as seeds (flax, pumpkin, sunflower, and sesame), whole grains (such as rye, oat, and barley), bran (such as wheat, oat, and rye), beans, fruits (especially berries), and cruciferous vegetables such as broccoli and cabbage [73][49].
The richest dietary source of plant lignans is flaxseed (Linum usatissimum), and crushing or milling flaxseed can increase lignan bioavailability [74][50].
Compared to isoflavones and lignans, coumestans are less prevalent in the human diet. Coumestans are primarily found in legume shoots and sprouts, primarily in clover and alfalfa, though small amounts have also been found in spinach and brussel sprouts [75][51]. Coumestrol is also found in trace levels in a variety of legumes, including split peas, pinto beans, lima beans, and soybean sprouts [75][51].
The most prevalent and studied stilbene, resveratrol, may be found in a number of plants and acts as a phytoalexin to ward off fungus infections. The skin of grapes (Vitis vinifera), red wine, and other highly pigmented fruit juices are the most recognized sources of resveratrol. Resveratrol is also present in pistachios, notably the papery skin surrounding the nut, and peanuts (Arachis). While flavonoids and resveratrol both have vascular effects that are frequently addressed, only the trans isomers of resveratrol have been found to have some phytoestrogenic effects [76][52].
Isoflavones are present in berries, wine, grains, and nuts, but are most abundant in soybeans, soy products, and other legumes [67,68][43][44].
Phytoestrogens, particularly isoflavones, exhibit both agonistic and antagonistic effects on ERβ and ERα receptors, depending on their concentration and affinity for various estrogen receptors [77][53]. This mechanism explains why phytoestrogens have a dual impact in ER-positive breast cancer cells, stimulating growth at low doses while inhibiting development at higher concentrations [78][54]. Coumestrol, genistein, and equol have a stronger affinity for ERβ [79,80][55][56].
Overall, phytoestrogens and their analogs inhibit cell cycle progression across different breast carcinomas by reducing mRNA or protein expression levels of cyclin (D1, E) and CDK (1, 2, 4, 6) and enhancing their inhibitors (p21, p27, p57) and tumor suppressor genes (APC, ATM, PTEN, SERPINB5) [73][49]. Even isoflavones, lignans, and resveratrol analogs influence cell cycle regulator expression, impacting different kinds of BC cell lines in vitro [81][57].
They also suppress the expression of oncogenic cyclin D1, as well as raise the levels of a variety of cyclin-dependent kinase inhibitors (p21, p27, and p57). Phytoestrogens, analogues, and derivatives may potentially influence BC behaviour, by interfering with estrogen production and metabolism as well as showing antiangiogenic, antimetastatic, and epigenetic effects. Furthermore, these bioactive molecules have the potential to reverse multi-drug resistance [81][57]. The benefits of phytoestrogens on human health, and particularly in BC patients, may also depend on their metabolism affected by the host’s microbiota present in the small and large intestine. For instance, genistein, equol, enterolignans, urolithins and other metabolites with higher binding affinity for estrogen receptors are more likely to yield beneficial effects.
Despite several research, the topic of whether phytoestrogens are useful or hurtful to people with BC remains unanswered: The answers are challenging and may vary with age, health state, and even gut microbial composition [82][58] (Table 2).
Table 2.
Interplay between phytoestrogens and their metabolites with microrganism.

Chemical Family

Molecules

Microrganisms

References

Lignans

Anhydrosecoisolariciresinol

Secoisolariciresinol diglucoside

Syringaresinol

C. methoxybenzovorans

B. pseudocatenulatum WC 401

Firmicutes

Bacteroidetes

[60,61,62,64][36][37][38][40]

Isoflavones

Coumestrol

Genistein

Equol

Daidzein

F. prausnitzii

Lactobacillus

Enterococcus

[63][39]

Steroids

Estradiol

Estrone

Collinsella, Edwardsiella, Alistipes, Bacteroides, Bifidobacterium, Citrobacter, Clostridium, Dermabacter, Escherichia, Faecalibacterium, Lactobacillus

]

][26][41][42]

Heavy metals

Arsenic

Lead

Cadmium

Bacteroides

Firmicutes

Proteobacteria

Altered gluconeogenesis

Lipogenesis

Inflammation

Body fat

[65,66][41][42]

BPA, Bisphenol A; BPS, Bisphenol S; DDT, dichloro-diphenyl-trichloroethane; DDE, Dichloro-diphenyl-dichloroethylene; PCB, polychlorinated biphenyl.

2. Phytoestrogens

Due to their chemical structures and/or activities similar to 17-estradiol (E2) [38[14][43][44],67,68], some plant-derived polyphenolic non-steroidal substances, defined phytoestrogens, are classified as endocrine disruptors, with both potentially favorable (reduced risk of osteoporosis, heart disease, and menopausal symptoms) and harmful health consequences [69,70][45][46].

,

Marvinbryantia

,

Propionibacterium

,

Roseburia, Tannerella

[22,83,84,85,86,87][59][60][61][62][63][64]

Prenylflavonoids

Xanthohumol

Desmethyxanthohumol

E. limosum

[88][65]

Stilbenes

Resveratrol

Trans-resveratrol

Dihydroresveratrol

3,4′–dihydroxybibenzyl,

3,4′-dihydroxy-trans-stilbene

Firmicutes

Bacteroidetes,

Actinobacteria

Verrucomicrobia,

Cyanobacteria

[89,90,,92,93][66][67]91[68][69][70]

References

  1. Kabir, E.R.; Rahman, M.S.; Rahman, I. A Review on Endocrine Disruptors and Their Possible Impacts on Human Health. Environ. Toxicol. Pharmacol. 2015, 40, 241–258.
  2. Monneret, C. What Is an Endocrine Disruptor? C. R. Biol. 2017, 340, 403–405.
  3. Gore, A.C.; Chappell, V.A.; Fenton, S.E.; Flaws, J.A.; Nadal, A.; Prins, G.S.; Toppari, J.; Zoeller, R.T. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr. Rev. 2015, 36, E1–E150.
  4. Cohn, B.A.; La Merrill, M.A.; Krigbaum, N.Y.; Wang, M.; Park, J.-S.; Petreas, M.; Yeh, G.; Hovey, R.C.; Zimmermann, L.; Cirillo, P.M. In Utero Exposure to Poly- and Perfluoroalkyl Substances (PFASs) and Subsequent Breast Cancer. Reprod. Toxicol. 2020, 92, 112–119.
  5. Heindel, J.J.; Newbold, R.; Schug, T.T. Endocrine Disruptors and Obesity. Nat. Rev. Endocrinol. 2015, 11, 653–661.
  6. Sargis, R.M. Metabolic Disruption in Context: Clinical Avenues for Synergistic Perturbations in Energy Homeostasis by Endocrine Disrupting Chemicals. Endocr. Disruptors 2015, 3, e1080788.
  7. Barouki, R. Endocrine Disruptors: Revisiting Concepts and Dogma in Toxicology. C. R. Biol. 2017, 340, 410–413.
  8. Williams, G.P.; Darbre, P.D. Low-Dose Environmental Endocrine Disruptors, Increase Aromatase Activity, Estradiol Biosynthesis and Cell Proliferation in Human Breast Cells. Mol. Cell. Endocrinol. 2019, 486, 55–64.
  9. Zama, A.M.; Uzumcu, M. Epigenetic Effects of Endocrine-Disrupting Chemicals on Female Reproduction: An Ovarian Perspective. Front. Neuroendocrinol. 2010, 31, 420–439.
  10. Giulivo, M.; Lopez de Alda, M.; Capri, E.; Barceló, D. Human Exposure to Endocrine Disrupting Compounds: Their Role in Reproductive Systems, Metabolic Syndrome and Breast Cancer. A Review. Environ. Res. 2016, 151, 251–264.
  11. Burks, H.; Pashos, N.; Martin, E.; Mclachlan, J.; Bunnell, B.; Burow, M. Endocrine Disruptors and the Tumor Microenvironment: A New Paradigm in Breast Cancer Biology. Mol. Cell. Endocrinol. 2017, 457, 13–19.
  12. Quagliariello, V.; Rossetti, S.; Cavaliere, C.; Di Palo, R.; Lamantia, E.; Castaldo, L.; Nocerino, F.; Ametrano, G.; Cappuccio, F.; Malzone, G.; et al. Metabolic Syndrome, Endocrine Disruptors and Prostate Cancer Associations: Biochemical and Pathophysiological Evidences. Oncotarget 2017, 8, 30606–30616.
  13. Rodgers, K.M.; Udesky, J.O.; Rudel, R.A.; Brody, J.G. Environmental Chemicals and Breast Cancer: An Updated Review of Epidemiological Literature Informed by Biological Mechanisms. Environ. Res. 2018, 160, 152–182.
  14. Diamanti-Kandarakis, E.; Bourguignon, J.-P.; Giudice, L.C.; Hauser, R.; Prins, G.S.; Soto, A.M.; Zoeller, R.T.; Gore, A.C. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr. Rev. 2009, 30, 293–342.
  15. Calaf, G.M.; Ponce-Cusi, R.; Aguayo, F.; Muñoz, J.P.; Bleak, T.C. Endocrine Disruptors from the Environment Affecting Breast Cancer. Oncol. Lett. 2020, 20, 19–32.
  16. Sengupta, S.; Obiorah, I.; Maximov, P.Y.; Curpan, R.; Jordan, V.C. Molecular Mechanism of Action of Bisphenol and Bisphenol A Mediated by Oestrogen Receptor Alpha in Growth and Apoptosis of Breast Cancer Cells. Br. J. Pharmacol. 2013, 169, 167–178.
  17. Mlynarcikova, A.; Macho, L.; Fickova, M. Bisphenol A Alone or in Combination with Estradiol Modulates Cell Cycle- and Apoptosis-Related Proteins and Genes in MCF7 Cells. Endocr. Regul. 2013, 47, 189–199.
  18. Katchy, A.; Pinto, C.; Jonsson, P.; Nguyen-Vu, T.; Pandelova, M.; Riu, A.; Schramm, K.-W.; Samarov, D.; Gustafsson, J.-Å.; Bondesson, M.; et al. Coexposure to Phytoestrogens and Bisphenol a Mimics Estrogenic Effects in an Additive Manner. Toxicol. Sci. 2014, 138, 21–35.
  19. Rocha, P.R.S.; Oliveira, V.D.; Vasques, C.I.; Dos Reis, P.E.D.; Amato, A.A. Exposure to Endocrine Disruptors and Risk of Breast Cancer: A Systematic Review. Crit. Rev. Oncol. Hematol. 2021, 161, 103330.
  20. Javed, A.; Lteif, A. Development of the Human Breast. Semin. Plast. Surg. 2013, 27, 5–12.
  21. Gulledge, C.C.; Burow, M.E.; McLachlan, J.A. Endocrine Disruption in Sexual Differentiation and Puberty. What Do Pseudohermaphroditic Polar Bears Have to Do with the Practice of Pediatrics? Pediatr. Clin. N. Am. 2001, 48, 1223–1240.
  22. Paulose, T.; Speroni, L.; Sonnenschein, C.; Soto, A.M. Estrogens in the Wrong Place at the Wrong Time: Fetal BPA Exposure and Mammary Cancer. Reprod. Toxicol. 2015, 54, 58–65.
  23. Palmer, J.R.; Wise, L.A.; Hatch, E.E.; Troisi, R.; Titus-Ernstoff, L.; Strohsnitter, W.; Kaufman, R.; Herbst, A.L.; Noller, K.L.; Hyer, M.; et al. Prenatal Diethylstilbestrol Exposure and Risk of Breast Cancer. Cancer Epidemiol. Biomarkers Prev. 2006, 15, 1509–1514.
  24. Thompson, W.D.; Janerich, D.T. Maternal Age at Birth and Risk of Breast Cancer in Daughters. Epidemiology 1990, 1, 101–106.
  25. Arrebola, J.P.; Belhassen, H.; Artacho-Cordón, F.; Ghali, R.; Ghorbel, H.; Boussen, H.; Perez-Carrascosa, F.M.; Expósito, J.; Hedhili, A.; Olea, N. Risk of Female Breast Cancer and Serum Concentrations of Organochlorine Pesticides and Polychlorinated Biphenyls: A Case-Control Study in Tunisia. Sci. Total Environ. 2015, 520, 106–113.
  26. Boada, L.D.; Zumbado, M.; Henríquez-Hernández, L.A.; Almeida-González, M.; Alvarez-León, E.E.; Serra-Majem, L.; Luzardo, O.P. Complex Organochlorine Pesticide Mixtures as Determinant Factor for Breast Cancer Risk: A Population-Based Case-Control Study in the Canary Islands (Spain). Environ. Health 2012, 11, 28.
  27. Yang, J.-Z.; Wang, Z.-X.; Ma, L.-H.; Shen, X.-B.; Sun, Y.; Hu, D.-W.; Sun, L.-X. The Organochlorine Pesticides Residues in the Invasive Ductal Breast Cancer Patients. Environ. Toxicol. Pharmacol. 2015, 40, 698–703.
  28. Cohn, B.A.; La Merrill, M.; Krigbaum, N.Y.; Yeh, G.; Park, J.-S.; Zimmermann, L.; Cirillo, P.M. DDT Exposure In Utero and Breast Cancer. J. Clin. Endocrinol. Metab. 2015, 100, 2865–2872.
  29. Aronson, K.J.; Miller, A.B.; Woolcott, C.G.; Sterns, E.E.; McCready, D.R.; Lickley, L.A.; Fish, E.B.; Hiraki, G.Y.; Holloway, C.; Ross, T.; et al. Breast Adipose Tissue Concentrations of Polychlorinated Biphenyls and Other Organochlorines and Breast Cancer Risk. Cancer Epidemiol. Biomarkers Prev. 2000, 9, 55–63.
  30. Recio-Vega, R.; Velazco-Rodriguez, V.; Ocampo-Gómez, G.; Hernandez-Gonzalez, S.; Ruiz-Flores, P.; Lopez-Marquez, F. Serum Levels of Polychlorinated Biphenyls in Mexican Women and Breast Cancer Risk. J. Appl. Toxicol. 2011, 31, 270–278.
  31. Eriksen, K.T.; McElroy, J.A.; Harrington, J.M.; Levine, K.E.; Pedersen, C.; Sørensen, M.; Tjønneland, A.; Meliker, J.R.; Raaschou-Nielsen, O. Urinary Cadmium and Breast Cancer: A Prospective Danish Cohort Study. J. Natl. Cancer Inst. 2017, 109, djw204.
  32. Nagata, C.; Nagao, Y.; Nakamura, K.; Wada, K.; Tamai, Y.; Tsuji, M.; Yamamoto, S.; Kashiki, Y. Cadmium Exposure and the Risk of Breast Cancer in Japanese Women. Breast. Cancer Res. Treat. 2013, 138, 235–239.
  33. Stellman, S.D.; Djordjevic, M.V.; Britton, J.A.; Muscat, J.E.; Citron, M.L.; Kemeny, M.; Busch, E.; Gong, L. Breast Cancer Risk in Relation to Adipose Concentrations of Organochlorine Pesticides and Polychlorinated Biphenyls in Long Island, New York. Cancer Epidemiol. Biomarkers Prev. 2000, 9, 1241–1249.
  34. Zhang, X.-L.; Liu, N.; Weng, S.-F.; Wang, H.-S. Bisphenol A Increases the Migration and Invasion of Triple-Negative Breast Cancer Cells via Oestrogen-Related Receptor Gamma. Basic Clin. Pharmacol. Toxicol. 2016, 119, 389–395.
  35. Jenkins, S.; Wang, J.; Eltoum, I.; Desmond, R.; Lamartiniere, C.A. Chronic Oral Exposure to Bisphenol A Results in a Nonmonotonic Dose Response in Mammary Carcinogenesis and Metastasis in MMTV-ErbB2 Mice. Environ. Health Perspect. 2011, 119, 1604–1609.
  36. Struijs, K.; Vincken, J.-P.; Gruppen, H. Bacterial Conversion of Secoisolariciresinol and Anhydrosecoisolariciresinol. J. Appl. Microbiol. 2009, 107, 308–317.
  37. Gaya, P.; Medina, M.; Sánchez-Jiménez, A.; Landete, J.M. Phytoestrogen Metabolism by Adult Human Gut Microbiota. Molecules 2016, 21, 1034.
  38. Roncaglia, L.; Amaretti, A.; Raimondi, S.; Leonardi, A.; Rossi, M. Role of Bifidobacteria in the Activation of the Lignan Secoisolariciresinol Diglucoside. Appl. Microbiol. Biotechnol. 2011, 92, 159–168.
  39. Guadamuro, L.; Delgado, S.; Redruello, B.; Flórez, A.B.; Suárez, A.; Martínez-Camblor, P.; Mayo, B. Equol Status and Changes in Fecal Microbiota in Menopausal Women Receiving Long-Term Treatment for Menopause Symptoms with a Soy-Isoflavone Concentrate. Front. Microbiol. 2015, 6, 777.
  40. Cho, S.-Y.; Kim, J.; Lee, J.H.; Sim, J.H.; Cho, D.-H.; Bae, I.-H.; Lee, H.; Seol, M.A.; Shin, H.M.; Kim, T.-J.; et al. Modulation of Gut Microbiota and Delayed Immunosenescence as a Result of Syringaresinol Consumption in Middle-Aged Mice. Sci. Rep. 2016, 6, 39026.
  41. Gálvez-Ontiveros, Y.; Páez, S.; Monteagudo, C.; Rivas, A. Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases. Nutrients 2020, 12, 1158.
  42. Velmurugan, G.; Ramprasath, T.; Gilles, M.; Swaminathan, K.; Ramasamy, S. Gut Microbiota, Endocrine-Disrupting Chemicals, and the Diabetes Epidemic. Trends Endocrinol. Metab. 2017, 28, 612–625.
  43. Dixon, R.A. Phytoestrogens. Annu. Rev. Plant Biol. 2004, 55, 225–261.
  44. Michel, T.; Halabalaki, M.; Skaltsounis, A.-L. New Concepts, Experimental Approaches, and Dereplication Strategies for the Discovery of Novel Phytoestrogens from Natural Sources. Planta Med. 2013, 79, 514–532.
  45. Lissin, L.W.; Cooke, J.P. Phytoestrogens and Cardiovascular Health. J. Am. Coll. Cardiol. 2000, 35, 1403–1410.
  46. Turner, J.V.; Agatonovic-Kustrin, S.; Glass, B.D. Molecular Aspects of Phytoestrogen Selective Binding at Estrogen Receptors. J. Pharm. Sci. 2007, 96, 1879–1885.
  47. Zhang, G.Q.; Chen, J.L.; Liu, Q.; Zhang, Y.; Zeng, H.; Zhao, Y. Soy intake is associated with lower endometrial cancer risk: A systematic review and meta-analysis of observational studies. Medicine 2015, 94, e2281.
  48. Messina, M. Soy and health update: Evaluation of the clinical and epidemiologic literature. Nutrients 2016, 8, 754.
  49. Meagher, L.P.; Bentz, E.K. Assessment of data on the lignan content of foods. J. Food Compos. Anal. 2000, 13, 935–947.
  50. Kuijsten, A.; Arts, I.C.; van’t Veer, P.; Hollman, P.C. The relative bioavailability of enterolignans in humans is enhanced by milling and crushing of flaxseed. J. Nutr. 2005, 135, 2812–2816.
  51. Poluzzi, E.; Piccinni, C.; Raschi, E.; Rampa, A.; Recanatini, M.; De Ponti, F. Phytoestrogens in postmenopause: The state of the art from a chemical, pharmacological and regulatory perspective. Curr. Med. Chem. 2014, 21, 417–436.
  52. Bagchi, D.; Das, D.K.; Tosaki, A.; Bagchi, M.; Kothari, S.C. Benefits of resveratrol in women’s health. Drugs Exp. Clin. Res. 2001, 27, 233–248.
  53. Fitzpatrick, L.A. Phytoestrogens—Mechanism of Action and Effect on Bone Markers and Bone Mineral Density. Endocrinol. Metab. Clin. North Am. 2003, 32, 233–252.
  54. Lecomte, S.; Demay, F.; Ferrière, F.; Pakdel, F. Phytochemicals Targeting Estrogen Receptors: Beneficial Rather Than Adverse Effects? Int. J. Mol. Sci. 2017, 18, 1381.
  55. Soto, A.M.; Sonnenschein, C.; Chung, K.L.; Fernandez, M.F.; Olea, N.; Serrano, F.O. The E-SCREEN Assay as a Tool to Identify Estrogens: An Update on Estrogenic Environmental Pollutants. Environ. Health Perspect. 1995, 103 (Suppl. 7), 113–122.
  56. Mueller, S.O.; Simon, S.; Chae, K.; Metzler, M.; Korach, K.S. Phytoestrogens and Their Human Metabolites Show Distinct Agonistic and Antagonistic Properties on Estrogen Receptor Alpha (ERalpha) and ERbeta in Human Cells. Toxicol. Sci. 2004, 80, 14–25.
  57. Basu, P.; Maier, C. Phytoestrogens and Breast Cancer: In Vitro Anticancer Activities of Isoflavones, Lignans, Coumestans, Stilbenes and Their Analogs and Derivatives. Biomed Pharmacother. 2018, 107, 1648–1666.
  58. Stojanov, S.; Kreft, S. Gut Microbiota and the Metabolism of Phytoestrogens. Rev. Bras. Farmacogn. 2020, 30, 145–154.
  59. Rietjens, I.M.C.M.; Louisse, J.; Beekmann, K. The Potential Health Effects of Dietary Phytoestrogens. Br. J. Pharmacol. 2017, 174, 1263–1280.
  60. Arrieta, M.-C.; Stiemsma, L.T.; Amenyogbe, N.; Brown, E.M.; Finlay, B. The Intestinal Microbiome in Early Life: Health and Disease. Front. Immunol. 2014, 5, 427.
  61. Selber-Hnatiw, S.; Sultana, T.; Tse, W.; Abdollahi, N.; Abdullah, S.; Al Rahbani, J.; Alazar, D.; Alrumhein, N.J.; Aprikian, S.; Arshad, R.; et al. Metabolic Networks of the Human Gut Microbiota. Microbiology 2020, 166, 96–119.
  62. Flores, R.; Shi, J.; Fuhrman, B.; Xu, X.; Veenstra, T.D.; Gail, M.H.; Gajer, P.; Ravel, J.; Goedert, J.J. Fecal Microbial Determinants of Fecal and Systemic Estrogens and Estrogen Metabolites: A Cross-Sectional Study. J. Transl. Med. 2012, 10, 253.
  63. Fuhrman, B.J.; Feigelson, H.S.; Flores, R.; Gail, M.H.; Xu, X.; Ravel, J.; Goedert, J.J. Associations of the Fecal Microbiome with Urinary Estrogens and Estrogen Metabolites in Postmenopausal Women. J. Clin. Endocrinol. Metab. 2014, 99, 4632–4640.
  64. Goedert, J.J.; Jones, G.; Hua, X.; Xu, X.; Yu, G.; Flores, R.; Falk, R.T.; Gail, M.H.; Shi, J.; Ravel, J.; et al. Investigation of the Association between the Fecal Microbiota and Breast Cancer in Postmenopausal Women: A Population-Based Case-Control Pilot Study. J. Natl. Cancer Inst. 2015, 107, djv147.
  65. Milligan, S.R.; Kalita, J.C.; Heyerick, A.; Rong, H.; De Cooman, L.; De Keukeleire, D. Identification of a Potent Phytoestrogen in Hops (Humulus Lupulus L.) and Beer. J. Clin. Endocrinol. Metab. 1999, 84, 2249–2252.
  66. Bode, L.M.; Bunzel, D.; Huch, M.; Cho, G.-S.; Ruhland, D.; Bunzel, M.; Bub, A.; Franz, C.M.A.P.; Kulling, S.E. In Vivo and in Vitro Metabolism of Trans-Resveratrol by Human Gut Microbiota. Am. J. Clin. Nutr. 2013, 97, 295–309.
  67. Chen, M.; Yi, L.; Zhang, Y.; Zhou, X.; Ran, L.; Yang, J.; Zhu, J.; Zhang, Q.; Mi, M. Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota. MBio 2016, 7, e02210-15.
  68. Sung, M.M.; Kim, T.T.; Denou, E.; Soltys, C.-L.M.; Hamza, S.M.; Byrne, N.J.; Masson, G.; Park, H.; Wishart, D.S.; Madsen, K.L.; et al. Improved Glucose Homeostasis in Obese Mice Treated with Resveratrol Is Associated with Alterations in the Gut Microbiome. Diabetes 2017, 66, 418–425.
  69. Sung, M.M.; Byrne, N.J.; Robertson, I.M.; Kim, T.T.; Samokhvalov, V.; Levasseur, J.; Soltys, C.-L.; Fung, D.; Tyreman, N.; Denou, E.; et al. Resveratrol Improves Exercise Performance and Skeletal Muscle Oxidative Capacity in Heart Failure. Am. J. Physiol. Heart Circ. Physiol. 2017, 312, H842–H853.
  70. Kim, T.T.; Parajuli, N.; Sung, M.M.; Bairwa, S.C.; Levasseur, J.; Soltys, C.-L.M.; Wishart, D.S.; Madsen, K.; Schertzer, J.D.; Dyck, J.R.B. Fecal Transplant from Resveratrol-Fed Donors Improves Glycaemia and Cardiovascular Features of the Metabolic Syndrome in Mice. Am. J. Physiol. Endocrinol. Metab. 2018, 315, E511–E519.
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