Microbial metabolism of dietary phenolic compounds in the colon

Abia R, Fry SC (2001) Degradation and metabolism of 14C-labelled proanthocyanidins from carob (Ceratonia siliqua) pods in the gastrointestinal tract of the rat. J Sci Food Agric 81:1156–1165

Adlercreutz H (2002) Phytoestrogens and cancer. Lancet Oncol 3:364–373

Adlercreutz H, van der Wildt J, Kinzel J, Attalla H, Wähälä K, Mäkelä T, Hase T, Fotsis T (1995) Lignan and isoflavonoid conjugates in human urine. J Steroid Biochem Mol Biol 52:97–103

Andreasen MF, Christensen LP, Meyer AS, Hansen Å (2000) Content of phenolic acids and ferulic acid dehydrodimers in 17 rye (Secale cereale L.) varieties. J Agric Food Chem 48:2837–2842

Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa M-T (2001a) Intestinal release and uptake of phenolic antioxidant diferulic acids. Free Radical Med 31:304–314

Andreasen MF, Kroon PA, Williamson G, Garcia-Conesa M-T (2001b) Esterase activity able to hydrolyze dietary antoxidant hydroxycinnamates is distributed along the intestine of mammals. J Agric Food Chem 49:5679–5684

Aura A-M, O’Leary KA, Williamson G, Ojala M, Bailey M, Puupponen-Pimiä R, Nuutila AM, Oksman-Caldentey K-M, Poutanen K (2002) Quercetin derivatives are deconjugated and converted to hydroxyphenylacetic acids but not methylated by human fecal microflora in vitro. J Agric Food Chem 50:1725–1730

Aura A-M, Martin-Lopez P, O’Leary KA, Williamson G, Oksman-Caldentey K-M, Poutanen K, Santos-Buelga C (2005a) In vitro metabolism of anthocyanins by human gut microflora. Eur J Nutr 44:133–142

Aura A-M, Karppinen S, Virtanen H, Forssell P, Heinonen S-M, Nurmi T, Adlercreutz H, Poutanen K (2005b) Processing of rye bran influences both the fermentaion of dietary fibre and the bioconversion of lignans by human faecal microbiota in vitro. J Sci Food Agric 85:2085–2093

Aura A-M, Oikarinen S, Mutanen M, Heinonen S-M, Adlercreutz HCT, Virtanen H, Poutanen KS (2006) Suitability of a batch in vitro fermentation model using human faecal microbiota for prediction of conversion of flaxseed lignans to enterolactone with reference to an in vivo rat model. Eur J Nutr 45:45–51

Aura A-M, Mattila I, Seppänen-Laakso T, Miettinen J, Oksman-Caldentey K-M, Orešič M (2008) Microbial metabolism of catechin stereoisomers by human faecal microbiota: Comparison of targeted analysis and a non-targeted metabolomics method. Phytochem Lett 1:18–22

Axelson M, Setchell KDR (1981) The excretion of lignans in rats – evidence for an intestinal bacterial source for this new group of compounds. FEBS Lett 123:337–342

Bach Knudsen KE, Serena A, Bjornbak Kjaer AK, Tetens I, Heinonen S-M, Nurmi T, Adlercreutz H (2003) Rye bread in the pigs enhances the formation of enterolactone and increases its levels in plasma, urine and feces. J Nutr 133:1368–1375

Begum AN, Nicolle C, Mila I, Lapierre C, Nagano K, Fukushima K, Heinonen S-M, Adlercreutz H, Rémésy C, Scalbert A (2004) Dietary lignins are precursors of mammalian lignans in rats. J Nutr 134:120–127

Blaut M, Clavel T (2007) Metabolic diversity of the intestinal microbiota: implications for health and disease. J Nutr 137:751S–755S

Borriello SP, Setchell KDR, Axelson M, Lawson AM (1985) Production and metabolism of lignans by the human faecal flora. J Appl Bacteriol 58:37–43

Cassidy A, Hanley B, Lamuela-Ravantos RM (2000) Isoflavones, lignans and stilbenes – origins, metabolism and potential importance to human health. J SciFood Agric 80:1044–1062

Cerda B, Llorach R, Ceron JJ, Espin JC, Tomas-Barberan FA (2003) Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eur J Nutr 42:18–28

Cerda B, Espin JC, Parra S, Martinez P, Tomas-Barberan FA (2004) The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur J Nutr 43:205–220

Cerda B, Tomas-Barneran FA, Espin JC (2005) Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts, and oak-aged wine in humans: identification of biomarkers and individual variability. J Agric Food Chem 53:227–235

Chesson A, Provan GJ, Russell WR, Scobbie L, Richardson AJ, Stewart C (1999) Hydroxycinnamic acids in the digestive tract of livestock and humans. J Sci Food Agric 79:373–378

Chung K-T, Wong T-Y, Wei C-I, Huang Y-W, Lin Y (1998) Tannins and human health: A Review. CRC Crit Rev Food Sci Nutr 38:421–464

Clavel T, Henderson G, Alpert C-A, Philippe C, Rigottier-Gois L, Doré J, Blaut M (2005) Intestinal bacterial communities that produce active estrogen-like compounds enterodiol and enterolactone in humans. Appl Environ Microbiol 71:6077–6085

Clavel T, Henderson G, Engst W, Doré J, Blaut M (2006a) Phylogeny of human intestinal bacteria that activate the dietary lignan secoisolariciresinol diglucoside. FEMS Microbiol 55:471–478

Clavel T, Borrmann D, Braune A, Doré J, Blaut M (2006b) Occurrence and activity of human intestinal bacteria involved in the conversion of dietary lignans. Anaerobe 12:140–147

Clavel T, Lippman R, Gavini F, Doré J, Blaut M (2007) Clostridium saccharogumia sp. nov. and Lactonifactor longoviformis gen. nov., sp. nov., two novel human faecal bacteria involved in the conversion of the dietary phytoestrogen secoisolariciresinol diglucoside. Syst Appl Microbiol 30:16–26

Clifford MN (2000a) Review. Anthocyanins – nature, occurrence and dietary burden. J Sci Food Agric 80:1063–1072

Clifford MN (2000b) Review. Chlorogenic acids and other cinnamates – nature, occurrence, dietary burden, absorption and metabolism. J Sci Food Agric 80:1033–1043

Clifford MN, Scalbert A (2000) Ellagitannins – nature, occurrence and dietary burden. J Sci Food Agric 80:1118–1125

Coldham NG, Darby C, Hows M, King LJ, Zhang A-Q, Sauer MJ (2002) Comparative metabolism of genistin in human and rat gut microflora: detection and identification of the end-products of metabolism. Xenobiotica 32:45–62

Couteau D, McCartney AL, Gibson GR, Williamson G, Faulds CB (2001) Isolation and characterization of human colonic bacteria able to hydrolyse chlorogenic acid. J Appl Microbiol 90:873–881

Das NP (1971) Studies on flavonoid metabolism. Absorption and metabolism of (+)-catechin in man. Biochem Pharmacol 20:3435–3445

Day AJ, Cañada FJ, Díaz JC, Kroon PA, Mclauchlan R, Faulds CB, Plumb GW, Morgan MRA, Williamson G (2000) Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase-phlorizin-hydrolase. FEBS Lett 468:166–170

Deprez S, Brezillon C, Rabot S, Philippe C, Mila I, Lapierre C, Scalbert A (2000) Polymeric proanthocyanidins are catabolized by human colonic microflora into low-molecular-weight phenolic acids. J Nutr 130:2733–2738

Donovan JL, Bell JR, Kasim-Karakas S, German JB, Walzem RL, Hansen RJ, Waterhouse AL (1999) Catechin is present as metabolites in human plasma after consumption of red wine. J Nutr 129:1662–1668

Doyle B, Griffiths LA (1980) The metabolism of ellagig acid in the rat. Xenobiotica 10:247–256

Felgines C, Talavéra S, Gonthier M-P, Texier O, Scalbert A, Lamaison J-L, Rémésy C (2003) Strawberry anthocyanins are recovered in urine as glucuro- and sulfoconjugates in humans. J Nutr 133:1296–1301

Fleschhut J, Kratzer F, Rechkemmer G, Kulling SE (2006) Stability and biotransformation of various dietary anthocyanins in vitro. Eur J Nutr 45:7–15

Glitsø LV, Mazur WM, Adlercreutz H, Wähälä K, Mäkelä T, Sandström B, Bach Knudsen KE (2000) Intestinal metabolism of rye lignans in pigs. Br J Nutr 84:429–437

Glässer G, Graefe EU, Struck F, Veit M, Gebhardt R (2002) Comparison of antioxidative capacities and inhibitory effects on cholesterol biosynthesis of quercetin and potential metabolites. Phytomedicine 9:33–40

Gonthier M-P, Donovan JL, Texier O, Felgines C, Remesy C, Scalbert A (2003a) Metabolism of dietary procyanidins in rats. Free Radic Biol Med 35:837–844

Gonthier M-P, Verny M-A, Besson C, Rémésy C, Scalbert A (2003b) Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats. J Nutr 133:1853–1859

Gonthier M-P, Remesy C, Scalbert A, Cheynier V, Souquet J-M, Poutanen K, Aura A-M (2006) Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric acids by human faecal microbiota in vitro. Biomed Pharmacother 60:536–540

Griffiths LA (1964) Studies on flavonoid metabolism. Identification of the metabolites of (+)-catechin in rat urine. Biochem J 92:173–179

Griffiths LA (1975) The role of the intestinal microflora in flavonoid metabolism. In: Farkas L, Gábor M, Kallay F (eds) Topics in flavonoid chemistry and biochemistry. Proceedings of the fourth Hungarian bioflavonoid symposium, Keszthely 1973, Amsterdam, Elsevier Publishing Company, pp 201–213

Griffiths LA (1982) Mammalian metabolism of flavonoids. In: Harborne JB, Marby TJ (eds) The flavonoids: recent advances in research. Chapman and Hall, London, pp 681–718

Griffiths LA, Smith GE (1972a) Metabolism of myricetin and related compounds in the rat metabolite formation in vivo and by intestinal microflora in vitro. Biochem J 130:141–151

Griffiths LA, Smith GE (1972b) Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by intestinal microflora in vitro. Biochem J 128:901–911

Groenewoud G, Hundt HKL (1986) The microbial metabolism of condensed (+)-catechins by rat-caecal microflora. Xenobiotica 16:99–107

Gross M, Pfeiffer M, Martini M, Campbell D, Slavin J, Potter J (1996) The quantitation of metabolites of quercetin flavonols in human urine. Cancer Epidemiol Biomark Prev 5:711–720

Guyton AC, Hall JE (1996) Gastrointestinal physiology. In: Guyton AC, Hall JE (eds) Textbook of medical physiology, 9th edn. W.B. Saunders Company, Philadelphia, pp 793–813

Harder H, Tetens I, Let MB, Meyer AS (2004) Rye bread intake elevates urinary excretion of ferulic acid in humans, but does not affect the susceptibility of LDL to oxidation. Eur J Nutr 43:230–236

Heinonen S, Wähälä K, Adlercreutz H (1999) 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 274:211–219

Heinonen S, Nurmi T, Liukkonen K, Poutanen K, Wähälä K, Deyama T, Nishibe S, Adlercreutz H (2001) In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem 49:3178–3186

Heinonen S-M, Wähälä K, Liukkonen K-H, Aura A-M, Poutanen K, Adlercreutz H (2004a) Studies of the in vitro intestinal metabolism of isoflavones aid in the identification of their urinary metabolites. J Agric Food Chem 52:2640–2646

Heinonen S-M, Wähälä K, Adlercreutz H (2004b) Identification of urinary metabolites of the red clover isoflavones formononetin and biochanin A in human subjects. J Agric Food Chem 52:6802–6809

Hollman PCH, Arts ICW (2000) Flavonols, flavones and flavanols – nature, occurrence and dietary burden. J Sci Food Agric 80:1081–1093

Hollman PCH, Katan MB (1998) Absorption, metabolism and bioavailability of flavonoids. In: Rice-Evans C, Packer L (eds) Flavonoids in health & disease, Marcel Dekker Inc, New York, pp 483–522

Ingram D, Sanders K, Kolybaba M, Lopez D (1997) Case-control study of phyto-oestrogens and breast cancer. Lancet 350:990–994

Jacobs E, Kulling SE, Metzler M (1999) Novel metabolites of the mammalian lignans enterolactone and enterodiol in human urine. J Steroid Biochem Mol Biol 68:211–218

Jenner AM, Rafter J, Halliwell B (2005) Human fecal water contents: the extent of colonic exposure to aromatic compounds. Free Radic Biol Med 38:763–772

Joannou GE, Kelly GE, Reeder AY, Waring M, Nelson C (1995) A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids. J Steroid Biochem Mol Biol 54:167–184

Johnsen NF, Hausner H, Olsen A, Tetens I, Christensen J, Bach Knudsen KE, Overvad K, Tjϕnneland A (2004) Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women. J Nutr 134:2691–2697

Juntunen KS, Mazur WM, Liukkonen KH, Uehara M, Poutanen KS, Adlercreutz HCT, Mykkänen HM (2000) Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women. Br J Nutr 84:839–846

Justesen U, Arrigoni E, Larsen BR, Amado R (2000) Degradation of flavonoid glycosides and aglycones duting in vitro fermentation with human faecal flora. Food Sci Technol 33:424–430

Karlsson PC, Huss U, Jenner A, Halliwell B, Bohlin L, Rafter JJ (2005) Human fecal water inhibits COX-2 in colonic HT-29 cells: Role of phenolic compounds. J Nutr 135:2343–2349

Keppler K, Humpf HU (2005) Metabolism of anthocyanins and their phenolic degradation products by the intestinal microflora. Bioorg Med Chem 13:5195–5205

Kern SM, Bennet RN, Needs PW, Mellon FA, Kroon PA, Garcia-Conesa M-T (2003) Characterization of metabolites of hydroxycinnamates in the in vitro model of human small intestinal epithelium Caco-2 cells. J Agric Food Chem 51:7884–7891

Kilkkinen A, Stumpf K, Pietinen P, Valsta LM, Tapanainen H, Adlercreutz H (2001) Determinants of serum enterolactone concentration. Am J Clin Nutr 73:1094–1100

Kilkkinen A, Pietinen P, Klaukka T,Virtamo J, Korhonen P, Adlercreutz H (2002) Use of oral antimicrobials decreases serum enterolactone concentration. Am J Epidemiol 155:472–477

Kilkkinen A, Valsta LM, Virtamo J, Stumpf K, Adlercreutz H, Pietinen P (2003) Intake of lignans is associated with serum enterolactone concentration in Finnish men and women. J Nutr 133:1830–1833

Kim D-H, Kobashi K (1986) The role of intestinal flora in metabolism of phenolic sulfate esters. Biochem Pharmacol 35:3507–3510

Kim D-H, Konishi L, Kobashi K (1986) Purification, characterization and reaction mechanism of novel arylsulfotransferase obtained from an anaerobic bacterium of human intestine. Biochim Biophys Acta 872:33–41

Kleessen B, Bezirtzoglou E, Mättö J (2000) Culture-based knowledge on biodiversity, development and stability of human gastrointestinal microflora. Microb Ecol Health Dis Suppl 2:53–63

Knust U, Spiegelhalder B, Strowitzki T, Owen RW (2006) Contribution of lignan intake to urine and serum enterolignan levels in German females: a randomised controlled intervention trial. Food Chem Toxicol 44:1057–1064

Konishi Y, Kobayashi S (2004) Microbial metabolites of ingested caffeic acid are absorbed by monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers. J Agric Food Chem 52:6418–6424

Krajka-Kuzniak V, Szaefer H, Baer-Dubowska W (2005) Modulation of cytochrome P450 and phase II enzymes by protocatechuic acid in mouse liver and kidney. Toxicology 216:24–31

Krishnamurty HG, Cheng KJ, Jones GA, Simpson FJ, Watkin JE (1970) Identification of products by the anaerobic degradation of rutin and related flavonoids by Butyrovibrio sp. C3. Can J Microbiol 16:759–767

Kroon PA, Faulds CB, Ryden P, Robertson JA, Williamson G (1997) Release of covalently bound ferulic acid from fiber in the human colon. J Agric Food Chem 45:661–667

Kroon PA, Clifford MN, Crozier A, Day AJ, Donovan JL, Manach C, Williamson G (2004) How should we assess the effects of exposure to dietary polyphenols in vitro? Am J Clin Nutr 80:15–21

Kuijsten A, Arts ICW, Vree TB, Hollman PCH (2005) Pharmacokinetics of enterolignans in healthy men and women consuming a single dose of secoisolariciresinol diglucoside. J Nutr 135:795–801

Kuijsten A, Arts ICW, Hollman PCH, van’t Veer P, Kampman E (2006) Plasma enterolignans are associated with lower colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 15:1132–1136

Lafay S, Gil-Izquierdo A, Manach C, Morand C, Besson C, Scalbert A (2006) Chlorogenic acid is absorbed in its intact form in the stomach of rats. J Nutr 136:1–6

Lampe JW (2003) Isoflavonoid and lignan phytoestrogens as dietary biomarkers. J Nutr 133:956S–964S

Larrosa M, Tomas-Barberan FA, Espin JC (2006a) The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco2 cells by using the mitochondrial pathway. J Nutr Biochem 17:611–625

Larrosa M, Gonzales-Sarrias A, Garcia-Conesa MT, Tomas-Barberan FA, Espin JC (2006b) Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. J Agric Food Chem 54:1611–1620

Lee M-J, Maliakal P, Chen L, Meng X, Bondoc FY, Prabhu S, Lambert G, Mohr S, Yang CS (2002) Pharmacokinetics of tea catechins after ingestion of green tea and (−)-epicatechin-3-gallate by humans: formation of different metabolites and individual variability. Cancer Epidemiol Biomark Prev 11:1025–1032

Levrat M-A, Texier O, Régerat F, Demigné C, Rémésy C (1993) Comparison of the effects of condensed tannin and pectin on cecal fermentation and lipid metabolism in the rat. Nutr Res 13:427–433

Liu C-L, Wang J-M, Chu C-Y, Cheng M-T, Tseng T-H (2002) In vivo protective effect of protocatechuic acid on tert-butylhydroperoxide-induced rat hepatotoxicity. Food Chem Toxicol 40:635–641

Lof M, Weiderpass E (2006) Epidemiologic evidence suggests that dietary phytoestrogen intake is associated with reduced risk of breast, endometrial, and prostate cancer. Nutr Res 26:609–619

Magee PJ, Rowland IR (2004) Phytoestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 91:513–531

Mazur WM, Uehara M, Wähälä K, Adlercreutz H (2000) Phyto-oestrogen content of berries, and plasma concentrations and urinary excretion of enterolactone after a single strawberry-meal in human subjects. Br J Nutr 83:381–387

Meng X, Sang S, Zhu N, Lu H, Sheng S, Lee M-J, Ho C-T, Yang CS (2002) Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem Res Toxicol 15:1041–1050

Meselhy MR, Nakamura N, Hattori M (1997) Biotransformation of (−)-epicatechin 3-O-gallate by human intestinal bacteria. Chem Pharm Bull 45:888–893

Milder IEJ, Arts ICW, van de Putte B, Venema DP, Hollman PCH (2005a) Lignan contents of Dutch plant foods: a database including lariciresinol, pinoresinol, secoisolariciresinol and matairesinol. Br J Clin Nutr 93:393–402

Milder IEJ, Feskens EJM, Arts ICW, Bueno de Mesquit BH, Hollman PCH, Kromhout D (2005b) Intake of plant lignans secoisolariciresinol, matairesinol, lariciresinol and pinoresinol in Dutch men and women. J Nutr 135:1202–1207

Milder IEJ, Kuijsteen A, Arts ICW, Feskens EJM, Kampman E, Hollman PCH, Van’t Veer P (2007) Relation between plasma enterodiol and enterolactone and dietary intake of lignans in a Dutch endoscopy-based population. J Nutr 137:1266–1271

Moazzami AA, Anderson RE, Kamal-Eldin A (2007) Quantitative NMR analysis of a sesamin catechol metabolite in human urine. J Nutr 137:940–944

Mulder TP, Rietveld AC, van Amelsvoort JM (2005) Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine. Am J Clin Nutr 81(Suppl):256S–260S

Nardini M, Cirillo E, Natella F, Scaccini C (2002) Absorption of phenolic acids in humans after coffee consumption. J Agric Food Chem 50:5735–5741

Natsume M, Osakabe N, Oyama M, Sasaki M, Baba S, Nakamura Y, Osawa T, Terao J (2003) Structures of (−)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-epicatechin: differences between human and rat. Free Radic Biol Med 34:840–849

Nemeth K, Plumb GW, Berrin JG, Juge R, Naim HY, Williamson G, Swallow DM, Kroon PA (2003) Deglycosylation by human intestinal epithelial cell β-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur J Nutr 42:29–42

Nesbitt PD, Lam Y, Thompson LU (1999) Human metabolism of mammalian lignan precursors in raw and processed flaxseed. Am J Clin Nutr 69:549–555

Oikarinen SI, Heinonen S-M, Nurmi T, Adlercreutz H, Mutanen M (2005) No effect on adenoma formation in Min mice after moderate amount of flaxseed. Eur J Nutr 44:273–280

Olthof MR, Hollman PCH, Buijsman MNCP, van Amelsvoort JMM, Katan MB (2003) Chlorogenic acid, quercetin-3-rutinoside and black tea phenols are extensively metabolized in humans. J Nutr 133:1806–1814

Peñalvo JL, Haajanen KM, Botting N, Adlercreutz H (2005a) Quantification of lignans in food using isotope dilution gas chromatography/mass spectrometry. J Agric Food Chem 53:9342–9347

Peñalvo JL, Heinonen S-M, Aura A-M, Adlercreutz H (2005b) Dietary sesamin is converted to enterolactone in humans. J Nutr 135:1056–1062

Peppercorn MA, Goldman P (1971) Caffeic acid metabolism by bacteria of the human gastrointestinal tract. J Bacteriol 108:996–1000

Pietinen P, Stumpf K, Männistö S, Kataja V, Uusitupa M, Adlercreutz H (2001) Serum enterolactone and risk of breast cancer: a case-control study in Eastern Finland. Cancer Epidemiol Biomark Prev 10:339–344

Plumb GW, Garcia-Conesa MT, Kroon PA, Rhodes M, Ridley S, Williamson G (1999) Metabolism of chlorogenic acid by human plasma, liver, intestine and gut microflora. J Sci Food Agric 79:390–392

Rechner AR, Kroner C (2005) Anthocyanins and colonic metabolites of dietary polyphenols inhibit platelet function. Thromb Res 116:327–334

Rechner AR, Smith MA, Kuhnle G, Gibson GR, Debham ES, Srai SKS, Moore KP, Rice-Evans CA (2004) Colonic metabolism of dietary polyphenols: influence of structure on microbial fermentation products. Free Radic Biol Med 36:212–225

Rios LY, Gonthier M-P, Rémesy C, Mila I, Lapierre C, Lazarus SA, Williamson G, Scalbert A (2003) Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am J Clin Nutr 77:912–918

Rondini L, Peyrat-Maillard M-N, Marsset-Baglieri A, Fromentin G, Durand P, Tomé D, Prost M, Berset C (2004) Bound ferulic acid from bran is more bioavailable than the free compound in rat. J Agric Food Chem 52:4338–4343

Rowland I, Wiseman H, Sanders T, Adlercreutz H, Bowey E (1999) Metabolism of oestrogens and phytoestrogens: role of the gut microflora. Biochem Soc Trans 27:304–308

Rowland I, Faughnan M, Hoey L, Wähälä K, Williamson G, Cassidy A (2003) Bioavailability of phytoestrogens. Br J Nutr 89(Suppl):S45–S58

Saarinen NM, Wärri A, Mäkelä SI, Eckerman C, Reunanen M, Ahotupa M, Salmi SM, Franke AA, Kangas L, Santti R (2000) Hydroxymatairesinol, a novel enterolactone precursor with antitumor properties from coniferous tree (Picea abies). Nutr Cancer 36:207–216

Saarinen NM, Huovinen R, Wärri A, Mäkelä SI, Valentin-Blasini L, Needham L, Eckerman C, Collan YU, Santti R (2001) Uptake and metabolism of hydroxymatairesinol in relation to its anticarcinogenicity in DMBA-induced rat mammary carcinoma model. Nutr Cancer 41:82–90

Saarinen NM, Huovinen R, Wärri A, Mäkelä SI, Valentin-Blasini L, Sjöholm R, Ämmälä J, Lehtilä R, Eckerman C, Collan YU, Santti R (2002a) Enterolactone inhibits the growth of 7,12,dimethylbenz(a) anthracene-induced mammary carcinoma in the rat. Mol Cancer Ther 1:869–876

Saarinen NM, Smeds A, Mäkelä SI, Ämmälä J, Hakala K, Pihlava J-M, Ryhänen E-L, Sjöholm R, Santti R (2002b) Structural determinants of plant lignans for the formation of enterolactone in vivo. J Chromatogr B 777:311–319

Saarinen NM, Penttinen PE, Smeds AI, Hurmerinta TT, Mäkelä SI (2005) Structural determinants of plant lignans for growth of mammary tumors and hormonal responses in vivo. J Steroid Biochem Mol Biol 93:209–219

Salminen S, Bouley C, Boutron-Ruault M-C, Cummings JH, Franck A, Gibson GR, Isolauri E, Moreau M-C, Roberfroid M, Rowland I (1998) Functional food science and gastrointestinal physiology and function. Br J Nutr 80(Suppl1):S147–S171

Santos-Buelga C, Scalbert A (2000) Procyanidins and tannin-like compounds – nature occurrence, dietary intake and effects on nutrition and health. J Sci Food Agric 80:1094–1117

Sawai Y, Kohsaka K, Nishiyama Y, Ando K (1987) Serum concentrations of rutoside metabolites after oral administration of a rutoside formulation to humans. Drug Res 37:729–732

Scalbert A (1991) Antimicrobial properties of tannins. Phytochemistry 30:3875–3883

Scalbert A, Williamson G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130:2073S–2085S

Scalbert A, Morand C, Manach C, Rémésy C (2002) Absorption and metabolism of polyphenols in the gut and impact on health. Biomed Pharmacother 56:276–282

Scheline RR (1970) The metabolism of (+)-catechin to hydroxyphenylvaleric acids by the intestinal microflora. Biochim Biophys Acta 222:228–230

Scheline RR (ed) (1978) Mammalian metabolism of plant xenobiotics. Academic press Inc., London, 489 pp

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

Schneider H, Schwiertz A, Collins MD, Blaut M (1999) Anaerobic transformation of quercetin-3-glucoside by bacteria from the human intestinal tract. Arch Microbiol 171:81–91

Seeram NP, Henning SM, Zhang Y, Suchard M, Li Z, Heber D (2006) Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 h. J Nutr 136:2481–2485

Setchell KDR, Lawson AM, Borrilello SP, Harkness R, Gordon H, Morgan DML, Kirk DN, Adlercreutz H, Andersson LC, Axelson M (1981) Lignan formation in man – microbial involvement and possible roles in relation to cancer. Lancet 2:4–7

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

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

Setchell KDR, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, Wolfe BE, Nechemias-Zimmer L, Brown NM, Lund TD, Handa RJ, Heubi JE (2005) S-Equol, a potent ligand for estrogen receptor β, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr 81:1072–1079

Stahl W, van den Berg H, Arthur J, Bast A, Dainty J, Faulks RM, Gärtner C, Haenen G, Hollman P et al (2002) Bioavailability and metabolism. Mol Aspects Med 23:39–100

Tanaka T, Kojima T, Suzui M, Mori H (1993) Chemoprevention of colon carcinogenesis by the natural product of a simple phenolic compound protocatechuic acid: suppressing effects on tumor development and biomarkers expression of colon tumorigenesis. Cancer Res 53:3908–3913

Tham DM, Gardner CD, Haskell WL (1998) Potential health benefits of dietary phytoestogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83:2223–2235

Thompson LU, Seidl MM, Rickard SE, Orcheson LJ, Fong HHS (1996) Antitumorigenic effects of a mammalian lignan precursor from flaxseed. Nutr Cancer 26:159–165

Tomás-Barberán FA, Clifford MN (2000a) Flavanones, chalcones, and dihydrochalcones – nature, occurrence and dietary burden. J Sci Food Agric 80:1073–1080

Tomás-Barberán FA, Clifford MN (2000b) Dietary hydroxybenzoic acid derivatives – nature, occurrence and dietary burden. J Sci Food Agric 80:1024–1032

Touillaud MS, Thiébaut ACM, Fournier A, Niravong M, Boutron-Ruault M-C, Clavel-Chapelon F (2007) Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status. J Natl Cancer Inst 99:475–486

Vanharanta M, Voutilainen S, Lakka TA, van der Lee M, Adlercreutz H, Salonen JT (1999) Risk of acute coronary events according to serum concentrations of enterolactone: a prospective population-based case-control study. Lancet 354:2112–2115

Vitaglione P, Donnarumma G, Napolitano A, Galvano F, Gallo A, Scalfi L, Fogliano V (2007) Protocatechuic acid is the major human metabolite of cyanidin-glucosides. J Nutr 137:2043–2048

Walle T, Walle UK, Halushka PV (2001) Carbon dioxide is the major metabolite of quercetin in humans. J Nutr 131:2648–2652

Walle T, Browning AM, Steed LL, Reed SG, Walle UK (2005) Flavonoid glycosides are hydrolyzed and thus activated on the oral cavity in humans. J Nutr 135:48–52

Wang L-Q, Meselhy MR, Li Y, Qin U-W, Hattori M (2000) Human intestinal bacteria capable of transforming secoisolariciresinol diglucoside to mammalian lignans, enterodiol and enterolactone. Chem Pharm Bull 48:1606–1610

Webb AL, McCullough ML (2005) Dietary lignans: potential role in cancer prevention. Nutr Cancer 51:117–131

Winter J, Popoff MR, Grimont P, Bokkenhauser VD (1991) Clostridium orbiscindens sp. nov., a human intestinal bacterium capable of cleaving the flavonoid C-ring. Int J Syst Bacteriol 41:355–357

World Health Organization (2003) Diet, nutrition and the prevention of chronic diseases. WHO Technical Report Series 916, Geneva, 149 pp

Xie L-H, Akao T, Hamasaki K, Deyama T, Hattori M (2003) Biotransformation of pinoresinol diglucoside to mammalian lignans by human intestinal microflora, and isolation of Enterococcus faecalis strain PDG-1 responsible for the transformation of (+)-pinoresinol to (+)-lariciresinol. Chem Pharm Bull 51:508–515

Xu X, Harris KS, Wang H-J, Murphy PA, Hendrich S (1995) Bioavailability of soybean isoflavones depends upon gut microflora in women. J Nutr 125:2307–2315

Zhao Z, Egashira Y, Sanada H (2004) Ferulic acid is quickly absorbed from rat stomach as the free form and then conjugated mainly in liver. J Nutr 134:3083–3088