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01-06-2019 | Original Contribution

Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes

Authors: Pedro Mena, Iziar A. Ludwig, Virginia B. Tomatis, Animesh Acharjee, Luca Calani, Alice Rosi, Furio Brighenti, Sumantra Ray, Julian L. Griffin, Les J. Bluck, Daniele Del Rio

Published in: European Journal of Nutrition | Issue 4/2019

Abstract

Purpose

There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated.

Methods

Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites.

Results

(Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids.

Conclusions

The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet.

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Del Rio D, Rodriguez-Mateos A, Spencer JPE, Tognolini M, Borges G, Crozier A (2013) Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 18(14):1818–1892. https://doi.org/10.1089/ars.2012.4581 CrossRefPubMedPubMedCentral

Rodriguez-Mateos A, Vauzour D, Krueger CG, Shanmuganayagam D, Reed J, Calani L, Mena P, Del Rio D, Crozier A (2014) Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Arch Toxicol 88(10):1803–1853. https://doi.org/10.1007/s00204-014-1330-7 CrossRefPubMed

Bresciani L, Martini D, Mena P, Tassotti M, Calani L, Brigati G, Brighenti F, Holasek S, Malliga D-E, Lamprecht M, Del Rio D (2017) Absorption profile of (poly)phenolic compounds after consumption of three food supplements containing 36 different fruits, vegetables, and berries. Nutrients 9(3):194. https://doi.org/10.3390/nu9030194 CrossRefPubMedCentral

Shi Y, Williamson G (2015) Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: a randomized, single-blinded, cross-over study. Food Funct 6:1443–1448. https://doi.org/10.1039/c5fo00155b CrossRefPubMed

Borel P, Desmarchelier C, Nowicki M, Bott R, Morange S, Lesavre N (2014) Interindividual variability of lutein bioavailability in healthy men: characterization, genetic variants involved, and relation with fasting plasma lutein concentration. Am J Clin Nutr 100(1):168–175. https://doi.org/10.3945/ajcn.114.085720 CrossRefPubMed

Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C, Steiling H, Williamson G, Crozier A (2009) Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos 37(8):1749–1758. https://doi.org/10.1124/dmd.109.028019 CrossRefPubMed

Stalmach A, Mullen W, Steiling H, Williamson G, Lean MEJ, Crozier A (2010) Absorption, metabolism, and excretion of green tea flavan-3-ols in humans with an ileostomy. Mol Nutr Food Res 54(3):323–334. https://doi.org/10.1002/mnfr.200900194 CrossRefPubMed

Stalmach A, Williamson G, Crozier A (2014) Impact of dose on the bioavailability of coffee chlorogenic acids in humans. Food Funct 5(8):1727–1737. https://doi.org/10.1039/c4fo00316k CrossRefPubMed

Williamson G, Clifford MN (2017) Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols. Biochem Pharmacol 39:24–39. https://doi.org/10.1016/j.bcp.2017.03.012 CrossRef

10.

Manach C, Milenkovic D, Van de Wiele T, Rodriguez-Mateos A, de Roos B, Garcia-Conesa MT, Landberg R, Gibney ER, Heinonen M, Tomas-Barberan F, Morand C (2016) Addressing the inter-individual variation in response to consumption of plant food bioactives—towards a better understanding of their role in healthy ageing and cardiometabolic risk reduction. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201600557 CrossRefPubMedPubMedCentral

11.

Setchell KD, Clerici C (2010) Equol: history, chemistry, and formation. J Nutr 140(7):1355S–1362S. https://doi.org/10.3945/jn.109.119776 CrossRefPubMedPubMedCentral

12.

Bolca S, Possemiers S, Maervoet V, Huybrechts I, Heyerick A, Vervarcke S, Depypere H, De Keukeleire D, Bracke M, De Henauw S, Verstraete W, Van de Wiele T (2007) Microbial and dietary factors associated with the 8-prenylnaringenin producer phenotype: a dietary intervention trial with fifty healthy post-menopausal Caucasian women. Br J Nutr 98(5):950–959. https://doi.org/10.1017/s0007114507749243 CrossRefPubMed

13.

Hazim S, Curtis PJ, Schar MY, Ostertag LM, Kay CD, Minihane AM, Cassidy A (2016) Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr 103(3):694–702. https://doi.org/10.3945/ajcn.115.125690 CrossRefPubMedPubMedCentral

14.

Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez MA, Selma MV, García-Conesa MT, Espín JC (2017) Urolithins, the rescue of “old” metabolites to understand a “new” concept: metabotypes as a nexus among phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201500901 CrossRefPubMed

15.

Gonzalez-Sarrias A, Garcia-Villalba R, Romo-Vaquero M, Alasalvar C, Orem A, Zafrilla P, Tomas-Barberan FA, Selma MV, Espin JC (2017) Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: a randomized clinical trial. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201600830 CrossRefPubMed

16.

Selma MV, Gonzalez-Sarrias A, Salas-Salvado J, Andres-Lacueva C, Alasalvar C, Orem A, Tomas-Barberan FA, Espin JC (2017) The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: comparison between normoweight, overweight-obesity and metabolic syndrome. Clin Nutr S0261-5614(17):30103–30106. https://doi.org/10.1016/j.clnu.2017.03.012 CrossRef

17.

Tomas-Barberan F, García-Villalba R, Quartieri A, Raimondi S, Amaretti A, Leonardi A, Rossi M (2013) In vitro transformation of chlorogenic acid by human gut microbiota. Mol Nutr Food Res 58(5):1122–1131. https://doi.org/10.1002/mnfr.201300441 CrossRefPubMed

18.

Del Rio D, Calani L, Cordero C, Salvatore S, Pellegrini N, Brighenti F (2010) Bioavailability and catabolism of green tea flavan-3-ols in humans. Nutrition 26(11–12):1110–1116. https://doi.org/10.1016/j.nut.2009.09.021 CrossRefPubMed

19.

Brindani N, Mena P, Calani L, Benzie I, Choi SW, Brighenti F, Zanardi F, Curti C, Del Rio D (2017) Synthetic and analytical strategies for the quantification of phenyl-gamma-valerolactone conjugated metabolites in human urine. Mol Nutr Food Res. https://doi.org/10.1002/mnfr.201700077 CrossRefPubMed

20.

Curti C, Brindani N, Battistini L, Sartori A, Pelosi G, Mena P, Brighenti F, Zanardi F, Del Rio D (2015) Catalytic, enantioselective vinylogous mukaiyama aldol reaction of furan-based dienoxy silanes: a chemodivergent approach to γ-valerolactone flavan-3-ol metabolites and δ-lactone analogues. Adv Synth Catal 357(18):4082–4092. https://doi.org/10.1002/adsc.201500705 CrossRef

21.

Westerhuis JA, van Velzen EJJ, Hoefsloot HCJ, Smilde AK (2008) Discriminant Q2 (DQ2) for improved discrimination in PLSDA models. Metabolomics 4(4):293–296. https://doi.org/10.1007/s11306-008-0126-2 CrossRef

22.

Acharjee A, Finkers R, Visser RG, Maliepaard C (2013) Comparison of regularized regression methods for omics data. Metabolomics 3:126–134. https://doi.org/10.4172/2153-0769.1000126 CrossRef

23.

Edmands WMB, Ferrari P, Rothwell JA, Rinaldi S, Slimani N, Barupal DK, Biessy C, Jenab M, Clavel-Chapelon F, Fagherazzi G, Boutron-Ruault MC, Katzke VA, Kühn T, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Palli D, Grioni S, Tumino R, Vineis P, Mattiello A, Romieu I, Scalbert A (2015) Polyphenol metabolome in human urine and its association with intake of polyphenol-rich foods across European countries. Am J Clin Nutr 102(4):905–913. https://doi.org/10.3945/ajcn.114.101881 CrossRefPubMed

24.

Ludwig IA, Mena P, Calani L, Cid C, Del Rio D, Lean MEJ, Crozier A (2014) Variations in caffeine and chlorogenic acid contents of coffees: what are we drinking? Food Funct 5(8):1718–1726. https://doi.org/10.1039/c4fo00290c CrossRefPubMed

25.

Zamora-Ros R, Rothwell JA, Scalbert A, Knaze V, Romieu I, Slimani N, Fagherazzi G, Perquier F, Touillaud M, Molina-Montes E, Huerta JM, Barricarte A, Amiano P, Menéndez V, Tumino R, de Magistris MS, Palli D, Ricceri F, Sieri S, Crowe FL, Khaw KT, Wareham NJ, Grote V, Li K, Boeing H, Förster J, Trichopoulou A, Benetou V, Tsiotas K, Bueno-de-Mesquita HB, Ros M, Peeters PH, Tjønneland A, Halkjær J, Overvad K, Ericson U, Wallström P, Johansson I, Landberg R, Weiderpass E, Engeset D, Skeie G, Wark P, Riboli E, González CA (2013) Dietary intakes and food sources of phenolic acids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr 110(8):1500–1511. https://doi.org/10.1017/S0007114513000688 CrossRefPubMed

26.

Roowi S, Stalmach A, Mullen W, Lean ME, Edwards CA, Crozier A (2010) Green tea flavan-3-ols: colonic degradation and urinary excretion of catabolites by humans. J Agric Food Chem 58(2):1296–1304. https://doi.org/10.1021/jf9032975 CrossRefPubMed

27.

van der Hooft JJ, de Vos RC, Mihaleva V, Bino RJ, Ridder L, de Roo N, Jacobs DM, van Duynhoven JP, Vervoort J (2012) Structural elucidation and quantification of phenolic conjugates present in human urine after tea intake. Anal Chem 84(16):7263–7271. https://doi.org/10.1021/ac3017339 CrossRefPubMed

28.

Urpi-Sarda M, Monagas M, Khan N, Llorach R, Lamuela-Raventós RM, Jáuregui O, Estruch R, Izquierdo-Pulido M, Andrés-Lacueva C (2009) Targeted metabolic profiling of phenolics in urine and plasma after regular consumption of cocoa by liquid chromatography–tandem mass spectrometry. J Chromatogr A 1216(43):7258–7267. https://doi.org/10.1016/j.chroma.2009.07.058 CrossRefPubMed

29.

Urpi-Sarda M, Boto-Ordóñez M, Queipo-Ortuño MI, Tulipani S, Corella D, Estruch R, Tinahones FJ, Andres-Lacueva C (2015) Phenolic and microbial-targeted metabolomics to discovering and evaluating wine intake biomarkers in human urine and plasma. Electrophoresis 36(18):2259–2268. https://doi.org/10.1002/elps.201400506 CrossRefPubMed

30.

Ulaszewska MM, Trost K, Stanstrup J, Tuohy KM, Franceschi P, Chong MFF, George T, Minihane AM, Lovegrove JA, Mattivi F (2016) Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet in adults: the FLAVURS trial. Metabolomics 12(2):1–22. https://doi.org/10.1007/s11306-015-0935-z CrossRef

31.

Meselhy MR, Nakamura N, Hattori M (1997) Biotransformation of (−)-epicatechin 3-O-gallate by human intestinal bacteria. Chem Pharm Bull 45(5):888–893. doiCrossRef

32.

Ward NC, Croft KD, Puddey IB, Hodgson JM (2004) Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic acid, an important metabolite of proanthocyanidins in humans. J Agric Food Chem 52(17):5545–5549. https://doi.org/10.1021/jf049404r CrossRefPubMed

33.

van Velzen EJJ, Westerhuis JA, Grün CH, Jacobs DM, Eilers PHC, Mulder TP, Foltz M, Garczarek U, Kemperman R, Vaughan EE, van Duynhoven JPM, Smilde AK (2014) Population-based nutrikinetic modeling of polyphenol exposure. Metabolomics 10:1059–1073. https://doi.org/10.1007/s11306-014-0645-y CrossRef

34.

Cueva C, Sánchez-Patán F, Monagas M, Walton GE, Gibson GR, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV (2013) In vitro fermentation of grape seed flavan-3-ol fractions by human faecal microbiota: changes in microbial groups and phenolic metabolites. FEMS Microbiol Ecol 83(3):792–805. https://doi.org/10.1111/1574-6941.12037 CrossRefPubMed

35.

Muñoz-González I, Jiménez-Girón A, Martín-Álvarez PJ, Bartolomé B, Moreno-Arribas MV (2013) Profiling of microbial-derived phenolic metabolites in human feces after moderate red wine intake. J Agric Food Chem 61(39):9470–9479. https://doi.org/10.1021/jf4025135 CrossRefPubMed

36.

Takagaki A, Nanjo F (2015) Bioconversion of (−)-epicatechin, (+)-epicatechin, (−)-catechin, and (+)-catechin by (−)-epigallocatechin-metabolizing bacteria. Biol Pharm Bull 38(5):789–794. https://doi.org/10.1248/bpb.b14-00813 CrossRefPubMed

37.

Gonthier MP, Donovan JL, Texier O, Felgines C, Remesy C, Scalbert A (2003) Metabolism of dietary procyanidins in rats. Free Radic Biol Med 35(8):837–844. https://doi.org/10.1016/s0891-5849(03)00394-0 CrossRefPubMed

38.

Kutschera M, Engst W, Blaut M, Braune A (2011) Isolation of catechin-converting human intestinal bacteria. J Appl Microbiol 111(1):165–175. https://doi.org/10.1111/j.1365-2672.2011.05025.x CrossRefPubMed

39.

Zamora-Ros R, Knaze V, Rothwell JA, Hémon B, Moskal A, Overvad K, Tjønneland A, Kyrø C, Fagherazzi G, Boutron-Ruault M-C, Touillaud M, Katzke V, Kühn T, Boeing H, Förster J, Trichopoulou A, Valanou E, Peppa E, Palli D, Agnoli C, Ricceri F, Tumino R, de Magistris MS, Peeters PHM, Bueno-de-Mesquita HB, Engeset D, Skeie G, Hjartåker A, Menéndez V, Agudo A, Molina-Montes E, Huerta JM, Barricarte A, Amiano P, Sonestedt E, Nilsson LM, Landberg R, Key TJ, Khaw K-T, Wareham NJ, Lu Y, Slimani N, Romieu I, Riboli E, Scalbert A (2016) Dietary polyphenol intake in Europe: the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Nutr 55(4):1359–1375. https://doi.org/10.1007/s00394-015-0950-x CrossRefPubMed

40.

Bai W, Wang C, Ren C (2014) Intakes of total and individual flavonoids by US adults. Int J Food Sci Nutr 65(1):9–20. https://doi.org/10.3109/09637486.2013.832170 CrossRefPubMed

Title: Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes
Authors: Pedro Mena
Iziar A. Ludwig
Virginia B. Tomatis
Animesh Acharjee
Luca Calani
Alice Rosi
Furio Brighenti
Sumantra Ray
Julian L. Griffin
Les J. Bluck
Daniele Del Rio
Publication date: 01-06-2019
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 4/2019
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-018-1683-4

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Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes

Abstract

Purpose

Methods

Results

Conclusions

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Abstract

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