Inter-individual variability in the production of flavan-3-ol colonic metabolites: preliminary elucidation of urinary metabotypes
- 446 Downloads
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.
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.
(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.
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.
KeywordsPolyphenols Green tea catechins Coffee caffeoylquinic acids Colonic microbiota Urinary phenotype Metabotypes
We thank the volunteers who participated in the study, Polly Page for her key role in study steering and management oversight, and the Volunteer Studies and Clinical Services and Sample Management Teams at MRC EWL for their assistance in the conduction of the study. We acknowledge Prof. Alan Crozier (University of California, Davis, USA) for his help with manuscript revision and data discussion. We are also grateful to Gary Williamson (University of Leeds, UK), Denis Barron (Nestle Research Center, Lausanne, Switzerland), and Takao Yokota (Teikyo University, Japan) for the generous gift of a number of phase II metabolites. Dr. Les Bluck, joint senior author for this work, played a fundamental role in the design of the original study; it is with much sadness that his death prevented him from seeing the research come to fruition.
PM and IL designed and conducted research, analyzed data, performed statistical analysis, and wrote the paper; VT designed and conducted research, analyzed data, and performed statistical analysis; AA performed statistical analysis; LC conducted research; AR, FB, and JLG provided critical review of the manuscript; SR designed and conducted research, and provided critical review; LJB designed research; DDR designed research and had primary responsibility for final content. All authors read and approved the final manuscript.
This work was partially funded by MRC core funding (Physiological Modelling of Metabolic Risk, MC_UP_A090_1005, and Nutrition, Surveys and Studies, MC_U105960384) and University of Parma core funding (FIL 2014-2017). P.M. was partially funded by a Grant of the Postdoctoral Fellowship Program from Fundación Séneca (Murcia Region, Spain). I.A.L. was supported by a postdoctoral fellowship funded by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20689).
Compliance with ethical standards
Conflict of interest
Authors declare no conflict of interest.
- 1.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 Google Scholar
- 2.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 Google Scholar
- 3.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 Google Scholar
- 5.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 Google Scholar
- 6.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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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. doiGoogle Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar
- 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 Google Scholar