Phytochemistry Reviews

, Volume 15, Issue 3, pp 425–444 | Cite as

The chemistry of gut microbial metabolism of polyphenols

  • Jan F. Stevens
  • Claudia S. Maier


Gut microbiota contribute to the metabolism of dietary polyphenols and affect the bioavailability of both the parent polyphenols and their metabolites. Although there is a large number of reports of specific polyphenol metabolites, relatively little is known regarding the chemistry and enzymology of the metabolic pathways utilized by specific microbial species and taxa, which is the focus of this review. Major classes of dietary polyphenols include monomeric and oligomeric catechins (proanthocyanidins), flavonols, flavanones, ellagitannins, and isoflavones. Gut microbial metabolism of representatives of these polyphenol classes can be classified as A- and C-ring cleavage (retro Claisen reactions), C-ring cleavage mediated by dioxygenases, dehydroxylations (decarboxylation or reduction reactions followed by release of H2O molecules), and hydrogenations of alkene moieties in polyphenols, such as resveratrol, curcumin, and isoflavones (mediated by NADPH-dependent reductases). The qualitative and quantitative metabolic output of the gut microbiota depends to a large extent on the metabolic capacity of individual taxa, which emphasizes the need for assessment of functional analysis in conjunction with determinations of gut microbiota compositions.


Catabolism Flavonoid Gut microbiota Mechanism Metabolic pathway 



The authors are in part supported by National Institutes of Health Grant No. R01AT009168.


  1. Amin HP, Czank C, Raheem S et al (2015) Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells. Mol Nutr Food Res 59:1095–1106PubMedCrossRefGoogle Scholar
  2. Appeldoorn MM, Vincken JP, Aura AM et al (2009) Procyanidin dimers are metabolized by human microbiota with 2-(3,4-dihydroxyphenyl)acetic acid and 5-(3,4-dihydroxyphenyl)-gamma-valerolactone as the major metabolites. J Agric Food Chem 57:1084–1092PubMedCrossRefGoogle Scholar
  3. Aura AM, Martin-Lopez P, O’Leary KA et al (2005) In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr 44:133–142PubMedCrossRefGoogle Scholar
  4. Barroso E, Sanchez-Patan F, Martin-Alvarez PJ et al (2013) Lactobacillus plantarum IFPL935 favors the initial metabolism of red wine polyphenols when added to a colonic microbiota. J Agric Food Chem 61:10163–10172PubMedCrossRefGoogle Scholar
  5. Bitsch I, Janssen M, Netzel M et al (2004) Bioavailability of anthocyanidin-3-glycosides following consumption of elderberry extract and blackcurrant juice. Int J Clin Pharmacol Ther 42:293–300PubMedCrossRefGoogle Scholar
  6. Bode LM, Bunzel D, Huch M et al (2013) In vivo and in vitro metabolism of trans-resveratrol by human gut microbiota. Am J Clin Nutr 97:295–309PubMedCrossRefGoogle Scholar
  7. Bottiglieri M, Keel C (2006) Characterization of PhlG, a hydrolase that specifically degrades the antifungal compound 2,4-diacetylphloroglucinol in the biocontrol agent Pseudomonas fluorescens CHA0. Appl Environ Microbiol 72:418–427PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bowater L, Fairhurst SA, Just VJ et al (2004) Bacillus subtilis YxaG is a novel Fe-containing quercetin 2,3-dioxygenase. FEBS Lett 557:45–48PubMedCrossRefGoogle Scholar
  9. Bowey E, Adlercreutz H, Rowland I (2003) Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats. Food Chem Toxicol 41:631–636PubMedCrossRefGoogle Scholar
  10. Brzezinski A, Debi A (1999) Phytoestrogens: the “natural” selective estrogen receptor modulators? Eur J Obstet Gynecol Reprod Biol 85:47–51PubMedCrossRefGoogle Scholar
  11. Bub A, Watzl B, Heeb D et al (2001) Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur J Nutr 40:113–120PubMedCrossRefGoogle Scholar
  12. Buckel W, Golding BT (2006) Radical enzymes in anaerobes. Annu Rev Microbiol 60:27–49PubMedCrossRefGoogle Scholar
  13. Cao G, Prior RL (1998) Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 44:1309–1315PubMedGoogle Scholar
  14. Carmona M, Zamarro MT, Blazquez B et al (2009) Anaerobic Catabolism of Aromatic Compounds: a Genetic and Genomic View. Microbiol Mol Biol Rev 73:71PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chadwick RW, George SE, Claxton LD (1992) Role of the gastrointestinal mucosa and microflora in the bioactivation of dietary and environmental mutagens or carcinogens. Drug Metab Rev 24:425–492PubMedCrossRefGoogle Scholar
  16. Czank C, Cassidy A, Zhang Q et al (2013) Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a (13) C-tracer study. Am J Clin Nutr 97:995–1003PubMedCrossRefGoogle Scholar
  17. Donovan JL, Manach C, Rios L et al (2002) Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3. Br J Nutr 87:299–306PubMedCrossRefGoogle Scholar
  18. Eggler AL, Gay KA, Mesecar AD (2008) Molecular mechanisms of natural products in chemoprevention: induction of cytoprotective enzymes by Nrf2. Mol Nutr Food Res 52:S84–S94PubMedGoogle Scholar
  19. Eggler AL, Small E, Hannink M et al (2009) Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J 422:171–180PubMedCrossRefGoogle Scholar
  20. Felgines C, Talavera S, Gonthier MP et al (2003) Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 133:1296–1301PubMedGoogle Scholar
  21. Fetzner S (2012) Ring-cleaving dioxygenases with a cupin fold. Appl Environ Microbiol 78:2505–2514PubMedPubMedCentralCrossRefGoogle Scholar
  22. Gall M, Thomsen M, Peters C et al (2014) Enzymatic conversion of flavonoids using bacterial chalcone isomerase and enoate reductase. Angew Chem Int Ed Engl 53:1439–1442PubMedCrossRefGoogle Scholar
  23. Garcia-Villalba R, Beltran D, Espin JC et al (2013) Time course production of urolithins from ellagic acid by human gut microbiota. J Agric Food Chem 61:8797–8806PubMedCrossRefGoogle Scholar
  24. Gardana C, Canzi E, Simonetti P (2014) R(–)–O–desmethylangolensin is the main enantiomeric form of daidzein metabolite produced by human in vitro and in vivo. J Chromatogr B Analyt Technol Biomed Life Sci 953–954:30–37PubMedCrossRefGoogle Scholar
  25. Gonthier MP, Cheynier V, Donovan JL et al (2003) Microbial aromatic acid metabolites formed in the gut account for a major fraction of the polyphenols excreted in urine of rats fed red wine polyphenols. J Nutr 133:461–467PubMedGoogle Scholar
  26. Gonzalez-Sarrias A, Gimenez-Bastida JA, Garcia-Conesa MT et al (2010) Occurrence of urolithins, gut microbiota ellagic acid metabolites and proliferation markers expression response in the human prostate gland upon consumption of walnuts and pomegranate juice. Mol Nutr Food Res 54:311–322PubMedCrossRefGoogle Scholar
  27. Goodrich KM, Neilson AP (2014) Simultaneous UPLC-MS/MS analysis of native catechins and procyanidins and their microbial metabolites in intestinal contents and tissues of male Wistar Furth inbred rats. J Chromatogr B Analyt Technol Biomed Life Sci 958:63–74PubMedCrossRefGoogle Scholar
  28. Gray NE, Sampath H, Zweig JA et al (2015) Centella asiatica attenuates amyloid-beta-induced oxidative stress and mitochondrial dysfunction. J Alzheimers Dis 45:933–946PubMedPubMedCentralGoogle Scholar
  29. Gu L, Kelm MA, Hammerstone JF et al (2004) Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J Nutr 134:613–617PubMedGoogle Scholar
  30. Hanske L, Loh G, Sczesny S et al (2009) The bioavailability of apigenin-7-glucoside is influenced by human intestinal microbiota in rats. J Nutr 139:1095–1102PubMedCrossRefGoogle Scholar
  31. Hanske L, Loh G, Sczesny S et al (2010) Recovery and metabolism of xanthohumol in germ-free and human microbiota-associated rats. Mol Nutr Food Res 54:1405–1413PubMedCrossRefGoogle Scholar
  32. Harini R, Pugalendi KV (2010) Antihyperglycemic effect of protocatechuic acid on streptozotocin-diabetic rats. J Basic Clin Physiol Pharmacol 21:79–91PubMedCrossRefGoogle Scholar
  33. Hassaninasab A, Hashimoto Y, Tomita-Yokotani K et al (2011) Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism. Proc Natl Acad Sci USA 108:6615–6620PubMedPubMedCentralCrossRefGoogle Scholar
  34. He YX, Huang L, Xue Y et al (2010) Crystal structure and computational analyses provide insights into the catalytic mechanism of 2,4-diacetylphloroglucinol hydrolase PhlG from Pseudomonas fluorescens. J Biol Chem 285:4603–4611PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hein EM, Rose K, van’t Slot G et al (2008) Deconjugation and degradation of flavonol glycosides by pig cecal microbiota characterized by Fluorescence in situ hybridization (FISH). J Agric Food Chem 56:2281–2290PubMedCrossRefGoogle Scholar
  36. Heinken A, Thiele I (2015) Anoxic conditions promote species-specific mutualism between gut microbes in silico. Appl Environ Microbiol 81:4049–4061PubMedPubMedCentralCrossRefGoogle Scholar
  37. Heinonen S-M, Hoikkala A, Wähälä K et al (2003) Metabolism of the soy isoflavones daidzein, genistein and glycitein in human subjects: identification of new metabolites having an intact isoflavonoid skeleton. J Steroid Biochem Mol Biol 87:285–299PubMedCrossRefGoogle Scholar
  38. Herles C, Braune A, Blaut M (2004) First bacterial chalcone isomerase isolated from Eubacterium ramulus. Arch Microbiol 181:428–434PubMedCrossRefGoogle Scholar
  39. Hirooka K, Fujita Y (2010) excess production of bacillus subtilis quercetin 2,3-dioxygenase affects cell viability in the presence of quercetin. Biosci Biotechnol Biochem 74:1030–1038PubMedCrossRefGoogle Scholar
  40. Hoffmann T, Troup B, Szabo A et al (1995) The anaerobic life of Bacillus subtilis: cloning of the genes encoding the respiratory nitrate reductase system. FEMS Microbiol Lett 131:219–225PubMedCrossRefGoogle Scholar
  41. Holder GM, Plummer JL, Ryan AJ (1978) The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat. Xenobiotica 8:761–768PubMedCrossRefGoogle Scholar
  42. Hong HA, Khaneja R, Tam NM et al (2009) Bacillus subtilis isolated from the human gastrointestinal tract. Res Microbiol 160:134–143PubMedCrossRefGoogle Scholar
  43. Huang D, Ou B, Prior RL (2005) The chemistry behind antioxidant capacity assays. J Agric Food Chem 53:1841–1856PubMedCrossRefGoogle Scholar
  44. Hur HG, Beger RD, Heinze TM et al (2002) Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of the isoflavonoid daidzein. Arch Microbiol 178:8–12PubMedCrossRefGoogle Scholar
  45. Ichiyanagi T, Shida Y, Rahman MM et al (2008) Effect on both aglycone and sugar moiety towards Phase II metabolism of anthocyanins. Food Chem 110:493–500PubMedCrossRefGoogle Scholar
  46. Ireson CR, Jones DJ, Orr S et al (2002) Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. Cancer Epidemiol Biomark Prev 11:105–111Google Scholar
  47. Jimenez-Giron A, Ibanez C, Cifuentes A et al (2015) Faecal metabolomic fingerprint after moderate consumption of red wine by healthy subjects. J Proteome Res 14:897–905PubMedCrossRefGoogle Scholar
  48. Joannou GE, Kelly GE, Reeder AY et al (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J Steroid Biochem Mol Biol 54:167–184PubMedCrossRefGoogle Scholar
  49. Kakkar S, Bais S (2014) A review on protocatechuic Acid and its pharmacological potential. ISRN Pharmacol 2014:952943PubMedPubMedCentralCrossRefGoogle Scholar
  50. Kang S, Joo C, Kim SM et al (2011) Oxidation of benzoins to benzoic acids using sodium hydride under oxygen atmosphere. Tetrahedron Lett 52:502–504CrossRefGoogle Scholar
  51. Karplus PA, Fox KM, Massey V (1995) Flavoprotein structure and mechanism. 8. Structure-function relations for old yellow enzyme. FASEB J 9:1518–1526PubMedGoogle Scholar
  52. Kavanagh KL, Jornvall H, Persson B et al (2008) Medium- and short-chain dehydrogenase/reductase gene and protein families: the SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol Life Sci 65:3895–3906PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kay CD, Mazza G, Holub BJ et al (2004) Anthocyanin metabolites in human urine and serum. Br J Nutr 91:933–942PubMedCrossRefGoogle Scholar
  54. Kim M, Han J (2014) Chiroptical study and absolute configuration of (–)–O–DMA produced from daidzein metabolism. Chirality 26:434–437PubMedCrossRefGoogle Scholar
  55. Kim M, Kim SI, Han J et al (2009) Stereospecific biotransformation of dihydrodaidzein into (3S)-equol by the human intestinal bacterium Eggerthella strain Julong 732. Appl Environ Microbiol 75:3062–3068PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kim M, Marsh EN, Kim SU et al (2010) Conversion of (3S,4R)-tetrahydrodaidzein to (3S)-equol by THD reductase: proposed mechanism involving a radical intermediate. Biochemistry 49:5582–5587PubMedCrossRefGoogle Scholar
  57. Knights D, Ward TL, McKinlay CE et al (2014) Rethinking “enterotypes”. Cell Host Microbe 16:433–437PubMedCrossRefGoogle Scholar
  58. Kumar H, Kim I-S, More SV et al (2014) Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep 31:109–139PubMedCrossRefGoogle Scholar
  59. Lee I-S, Lim J, Gal J et al (2011) Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells. Neurochem Int 58:153–160PubMedCrossRefGoogle Scholar
  60. Lee-Hilz YY, Boerboom AM, Westphal AH et al (2006) Pro-oxidant activity of flavonoids induces EpRE-mediated gene expression. Chem Res Toxicol 19:1499–1505PubMedCrossRefGoogle Scholar
  61. Legette L, Ma L, Reed RL et al (2012) Pharmacokinetics of xanthohumol and metabolites in rats after oral and intravenous administration. Mol Nutr Food Res 56:466–474PubMedPubMedCentralCrossRefGoogle Scholar
  62. Legette LL, Luna AY, Reed RL et al (2013) Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats. Phytochemistry 91:236–241PubMedCrossRefGoogle Scholar
  63. Legette LL, Prasain J, King J et al (2014) Pharmacokinetics of equol, a soy isoflavone metabolite, changes with the form of equol (dietary versus intestinal production) in ovariectomized rats. J Agric Food Chem 62:1294–1300PubMedPubMedCentralCrossRefGoogle Scholar
  64. Lin HH, Chen JH, Chou FP et al (2011) Protocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/NF-kappaB pathway and MMP-2 production by targeting RhoB activation. Br J Pharmacol 162:237–254PubMedPubMedCentralCrossRefGoogle Scholar
  65. Ma Z-C, Hong Q, Wang Y-G et al (2010) ferulic acid protects human umbilical vein endothelial cells from radiation induced oxidative stress by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. Biol Pharm Bull 33:29–34PubMedCrossRefGoogle Scholar
  66. Margalef M, Pons Z, Muguerza B et al (2014) A rapid method to determine colonic microbial metabolites derived from grape flavanols in rat plasma by liquid chromatography-tandem mass spectrometry. J Agric Food Chem 62:7698–7706PubMedCrossRefGoogle Scholar
  67. Maruo T, Sakamoto M, Ito C et al (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 58:1221–1227PubMedCrossRefGoogle Scholar
  68. Masella R, Santangelo C, D’Archivio M et al (2012) Protocatechuic acid and human disease prevention: biological activities and molecular mechanisms. Curr Med Chem 19:2901–2917PubMedCrossRefGoogle Scholar
  69. Matthies A, Loh G, Blaut M et al (2012) Daidzein and genistein are converted to equol and 5-hydroxy-equol by human intestinal Slackia isoflavoniconvertens in gnotobiotic rats. J Nutr 142:40–46PubMedCrossRefGoogle Scholar
  70. McInerney MJ, Gieg LM (2004) An overview of anaerobic metabolism. In: Nakano MM, Zuber P (eds) Strict and facultatie anaerobes: medical and environmental aspects. Horiz Biosci, Norfolk, pp 27–66Google Scholar
  71. Mertens-Talcott SU, Rios J, Jilma-Stohlawetz P et al (2008) Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers. J Agric Food Chem 56:7796–7802PubMedCrossRefGoogle Scholar
  72. Milligan SR, Kalita JC, Pocock V et al (2000) The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 85:4912–4915PubMedCrossRefGoogle Scholar
  73. Mulek M, Hogger P (2015) Highly sensitive analysis of polyphenols and their metabolites in human blood cells using dispersive SPE extraction and LC-MS/MS. Anal Bioanal Chem 407:1885–1899PubMedCrossRefGoogle Scholar
  74. Nunez-Sanchez MA, Garcia-Villalba R, Monedero-Saiz T et al (2014) Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol Nutr Food Res 58:1199–1211PubMedCrossRefGoogle Scholar
  75. Oppermann U, Filling C, Hult M et al (2003) Short-chain dehydrogenases/reductases (SDR): the 2002 update. Chem Biol Interact 143–144:247–253PubMedCrossRefGoogle Scholar
  76. Peiffer DS, Zimmerman NP, Wang LS et al (2014) Chemoprevention of esophageal cancer with black raspberries, their component anthocyanins, and a major anthocyanin metabolite, protocatechuic acid. Cancer Prev Res (Phila) 7:574–584CrossRefGoogle Scholar
  77. Peng X, Zhang Z, Zhang N et al (2014) In vitro catabolism of quercetin by human fecal bacteria and the antioxidant capacity of its catabolites. Food Nutr Res 58:23406CrossRefGoogle Scholar
  78. Pompella A, Sies H, Wacker R et al (2014) The use of total antioxidant capacity as surrogate marker for food quality and its effect on health is to be discouraged. Nutrition 30:791–793PubMedCrossRefGoogle Scholar
  79. Possemiers S, Heyerick A, Robbens V et al (2005) Activation of proestrogens from hops (Humulus lupulus L.) by intestinal microbiota; conversion of isoxanthohumol into 8-prenylnaringenin. J Agric Food Chem 53:6281–6288PubMedCrossRefGoogle Scholar
  80. Possemiers S, Bolca S, Grootaert C et al (2006) The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. J Nutr 136:1862–1867PubMedGoogle Scholar
  81. Rafii F (2015) The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites 5:56–73PubMedPubMedCentralCrossRefGoogle Scholar
  82. Rasmussen SE, Frederiksen H, Struntze Krogholm K et al (2005) Dietary proanthocyanidins: occurrence, dietary intake, bioavailability, and protection against cardiovascular disease. Mol Nutr Food Res 49:159–174PubMedCrossRefGoogle Scholar
  83. Rechner AR, Smith MA, Kuhnle G et al (2004) Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radic Biol Med 36:212–225PubMedCrossRefGoogle Scholar
  84. Schaab MR, Barney BM, Francisco WA (2006) Kinetic and spectroscopic studies on the quercetin 2,3-dioxygenase from Bacillus subtilis. Biochemistry 45:1009–1016PubMedCrossRefGoogle Scholar
  85. Schneider H, Simmering R, Hartmann L et al (2000) Degradation of quercetin-3-glucoside in gnotobiotic rats associated with human intestinal bacteria. J Appl Microbiol 89:1027–1037PubMedCrossRefGoogle Scholar
  86. Schnider-Keel U, Seematter A, Maurhofer M et al (2000) Autoinduction of 2,4-diacetylphloroglucinol biosynthesis in the biocontrol agent Pseudomonas fluorescens CHA0 and repression by the bacterial metabolites salicylate and pyoluteorin. J Bacteriol 182:1215–1225PubMedPubMedCentralCrossRefGoogle Scholar
  87. Schoefer L, Mohan R, Braune A et al (2002) Anaerobic C-ring cleavage of genistein and daidzein by Eubacterium ramulus. FEMS Microbiol Lett 208:197–202PubMedCrossRefGoogle Scholar
  88. Schoefer L, Braune A, Blaut M (2004) Cloning and expression of a phloretin hydrolase gene from Eubacterium ramulus and characterization of the recombinant enzyme. Appl Environ Microbiol 70:6131–6137PubMedPubMedCentralCrossRefGoogle Scholar
  89. Schroder C, Matthies A, Engst W et al (2013) Identification and expression of genes involved in the conversion of daidzein and genistein by the equol-forming bacterium Slackia isoflavoniconvertens. Appl Environ Microbiol 79:3494–3502PubMedPubMedCentralCrossRefGoogle Scholar
  90. Selma MV, Beltran D, Garcia-Villalba R et al (2014a) Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species. Food Funct 5:1779–1784PubMedCrossRefGoogle Scholar
  91. Selma MV, Tomas-Barberan FA, Beltran D et al (2014b) Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut. Int J Syst Evol Microbiol 64:2346–2352PubMedCrossRefGoogle Scholar
  92. Serra A, Macia A, Romero MP et al (2012) Metabolic pathways of the colonic metabolism of flavonoids (flavonols, flavones and flavanones) and phenolic acids. Food Chem 130:383–393CrossRefGoogle Scholar
  93. Setchell KD, Clerici C, Lephart ED et al (2005) S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr 81:1072–1079PubMedGoogle Scholar
  94. Shimada Y, Yasuda S, Takahashi M et al (2010) Cloning and expression of a novel NADP(H)-dependent daidzein reductase, an enzyme involved in the metabolism of daidzein, from equol-producing Lactococcus strain 20-92. Appl Environ Microbiol 76:5892–5901PubMedPubMedCentralCrossRefGoogle Scholar
  95. Shimada Y, Takahashi M, Miyazawa N et al (2011) Identification of two novel reductases involved in equol biosynthesis in Lactococcus strain 20-92. J Mol Microbiol Biotechnol 21:160–172PubMedCrossRefGoogle Scholar
  96. Shimada Y, Takahashi M, Miyazawa N et al (2012) Identification of a novel dihydrodaidzein racemase essential for biosynthesis of equol from daidzein in Lactococcus sp. strain 20-92. Appl Environ Microbiol 78:4902–4907PubMedPubMedCentralCrossRefGoogle Scholar
  97. Shisler KA, Broderick JB (2014) Glycyl radical activating enzymes: structure, mechanism, and substrate interactions. Arch Biochem Biophys 546:64–71PubMedPubMedCentralCrossRefGoogle Scholar
  98. Silverman RB (2002) The organic chemistry of enzyme-catalyzed reactions. Academic Press, LondonGoogle Scholar
  99. Spencer JP, Chaudry F, Pannala AS et al (2000) Decomposition of cocoa procyanidins in the gastric milieu. Biochem Biophys Res Commun 272:236–241PubMedCrossRefGoogle Scholar
  100. Steiner RA, Kalk KH, Dijkstra BW (2002) Anaerobic enzyme·substrate structures provide insight into the reaction mechanism of the copper-dependent quercetin 2,3-dioxygenase. Proc Natl Acad Sci 99:16625–16630PubMedPubMedCentralCrossRefGoogle Scholar
  101. Sun YJ, Huang QQ, Li P et al (2015) Catalytic dioxygenation of flavonol by M-complexes (M=Mn, Fe, Co, Ni, Cu and Zn)—mimicking the M-substituted quercetin 2,3-dioxygenase. Dalton Trans 44:13926–13938PubMedCrossRefGoogle Scholar
  102. Takagaki A, Nanjo F (2013) Catabolism of (+)-catechin and (−)-epicatechin by rat intestinal microbiota. J Agric Food Chem 61:4927–4935PubMedCrossRefGoogle Scholar
  103. Taylor CT, Colgan SP (2007) Hypoxia and gastrointestinal disease. J Mol Med (Berl) 85:1295–1300CrossRefGoogle Scholar
  104. Thomsen M, Tuukkanen A, Dickerhoff J et al (2015) Structure and catalytic mechanism of the evolutionarily unique bacterial chalcone isomerase. Acta Crystallogr D Biol Crystallogr 71:907–917PubMedCrossRefGoogle Scholar
  105. Toh H, Oshima K, Suzuki T et al (2013) Complete genome sequence of the equol-producing bacterium adlercreutzia equolifaciens DSM 19450T. Genome Announc 1:e00742PubMedPubMedCentralCrossRefGoogle Scholar
  106. Tomas-Barberan FA, Garcia-Villalba R, Gonzalez-Sarrias A et al (2014) Ellagic acid metabolism by human gut microbiota: consistent observation of three urolithin phenotypes in intervention trials, independent of food source, age, and health status. J Agric Food Chem 62:6535–6538PubMedCrossRefGoogle Scholar
  107. Truchado P, Larrosa M, Garcia-Conesa MT et al (2012) Strawberry processing does not affect the production and urinary excretion of urolithins, ellagic acid metabolites, in humans. J Agric Food Chem 60:5749–5754PubMedCrossRefGoogle Scholar
  108. Tsao SM, Hsia TC, Yin MC (2014) Protocatechuic acid inhibits lung cancer cells by modulating FAK, MAPK, and NF-kappaB pathways. Nutr Cancer 66:1331–1341PubMedCrossRefGoogle Scholar
  109. Tsuji H, Moriyama K, Nomoto K et al (2010) Isolation and characterization of the equol-producing bacterium Slackia sp. strain NATTS. Arch Microbiol 192:279–287PubMedCrossRefGoogle Scholar
  110. Tsuji H, Moriyama K, Nomoto K et al (2012) Identification of an enzyme system for daidzein-to-equol conversion in Slackia sp. strain NATTS. Appl Environ Microbiol 78:1228–1236PubMedPubMedCentralCrossRefGoogle Scholar
  111. Tulipani S, Urpi-Sarda M, Garcia-Villalba R et al (2012) Urolithins are the main urinary microbial-derived phenolic metabolites discriminating a moderate consumption of nuts in free-living subjects with diagnosed metabolic syndrome. J Agric Food Chem 60:8930–8940PubMedCrossRefGoogle Scholar
  112. Turnbaugh PJ, Ridaura VK, Faith JJ et al (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1:6ra14PubMedPubMedCentralGoogle Scholar
  113. Uchiyama S, Ueno T, Suzuki T (2013) Equol-producing lactic acid bacteria-containing composition. PCT/JP2004/009484Google Scholar
  114. Ulbrich K, Reichardt N, Braune A et al (2015) The microbial degradation of onion flavonol glucosides and their roasting products by the human gut bacteria Eubacterium ramulus and Flavonifractor plautii. Food Res Int 67:349–355CrossRefGoogle Scholar
  115. van Duynhoven J, Vaughan EE, Jacobs DM et al (2011) Metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci USA 108(Suppl 1):4531–4538PubMedPubMedCentralCrossRefGoogle Scholar
  116. Varì R, D’Archivio M, Filesi C et al (2011) Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages. J Nutr Biochem 22:409–417PubMedCrossRefGoogle Scholar
  117. Wang LS, Stoner GD (2008) Anthocyanins and their role in cancer prevention. Cancer Lett 269:281–290PubMedPubMedCentralCrossRefGoogle Scholar
  118. Wang XL, Kim KT, Lee JH et al (2004) C-ring cleavage of isoflavones daidzein and genistein by a newly-isolated human intestinal bacterium Eubacterium ramulus Julong 601. J Microbiol Biotechnol 14:766–771Google Scholar
  119. Wang D, Xia M, Yan X et al (2012) Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circ Res 111:967–981PubMedCrossRefGoogle Scholar
  120. Williamson G, Clifford MN (2010) Colonic metabolites of berry polyphenols: the missing link to biological activity? Br J Nutr 104(Suppl 3):S48–S66PubMedCrossRefGoogle Scholar
  121. Woodward GM, Needs PW, Kay CD (2011) Anthocyanin-derived phenolic acids form glucuronides following simulated gastrointestinal digestion and microsomal glucuronidation. Mol Nutr Food Res 55:378–386PubMedCrossRefGoogle Scholar
  122. Xu J, Gordon JI (2003) Honor thy symbionts. Proc Natl Acad Sci USA 100:10452–10459PubMedPubMedCentralCrossRefGoogle Scholar
  123. Yin MC, Lin CC, Wu HC et al (2009) Apoptotic effects of protocatechuic acid in human breast, lung, liver, cervix, and prostate cancer cells: potential mechanisms of action. J Agric Food Chem 57:6468–6473PubMedCrossRefGoogle Scholar
  124. Yokoyama S, Oshima K, Nomura I et al (2011) Complete genomic sequence of the equol-producing bacterium Eggerthella sp. strain YY7918, isolated from adult human intestine. J Bacteriol 193:5570–5571PubMedPubMedCentralCrossRefGoogle Scholar
  125. 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 51:765–781PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesOregon State UniversityCorvallisUSA
  2. 2.Department of ChemistryOregon State UniversityCorvallisUSA
  3. 3.Linus Pauling InstituteOregon State UniversityCorvallisUSA

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