Non-extractable polyphenols produce gut microbiota metabolites that persist in circulation and show anti-inflammatory and free radical-scavenging effects

Trends in Food Science and Technology

Volumn 69, Issue , 2017, Pages 281-288

  González Sarrías, Antonio ^a   Espín, Juan Carlos ^a   Tomás Barberán, Francisco A ^a  

^a RESEARCH GROUP ON QUALITY   (Spain)

Author keywords

Anti inflammatory; Antioxidant; Ellagitannin; Gut microbiota metabolites; Macroantioxidants; Proanthocyanidin

Indexed keywords

ANTIOXIDANTS; BIOMOLECULES; FLAVONOIDS; METABOLITES;

ANTI-INFLAMMATORIES; ELLAGITANNIN; GUT MICROBIOTA; MACROANTIOXIDANTS; PROANTHOCYANIDINS;

FREE RADICALS;

EID: 85024120240     PISSN: 09242244     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tifs.2017.07.010     Document Type: Note

References (59)

1. Aragonès, G., Danesi, F., Del Rio, D., Mena, P., The importance of studying cell metabolism when testing the bioactivity of phenolic compounds. Trends in Food Science & Technology, 2017 https://doi.org/10.1016/j.tifs.2017.02.001.
2. Arranz, S., Saura-Calixto, F., Shaha, S., Kroon, P.A., High content of non-extractable polyphenols in fruits suggest that polyphenols content of plant foods has been underestimated. Journal of Agricultural and Food Chemistry 57:16 (2009), 7298–7303.
3. Arumugan, M., Raes, J., Pelletier, F., Le Pastier, J., Yamada, T., Mende, D.R., et al. Enteotypes of the human gut microbiome. Nature 473:7346 (2011), 174–180.
4. Baba, S., Osakabe, N., Natsume, M., Terao, J., Absorption and urinary excretion of procyanidin B2 [epicatechin-(4beta-8)-epicatechin] in rats. Free Radicals in Biology and Medicine 33:1 (2002), 142–148.
5. Bialonska, D., Kasimsetty, S.G., Khan, S.I., Ferreira, D., Urolithins, intestinal microbial metabolites of pomegranate-ellagitannins, exhibit potent antioxidant activity in a cell-based assay. Journal of Agricultural and Food Chemistry 57:21 (2009), 10181–10186.
6. Braune, A., Blaut, M., Bacterial species involved in the conversion of dietary flavonoids in the human gut. Gut Microbes 7:3 (2016), 216–234.
7. Brett, G.M., Hollands, W., Needs, P.W., Teucher, B., Dainty, J.R., Davis, B.D., et al. Absorption, metabolism and excretion of flavanones from single portions of orange fruit and effects of anthropometric variables and contraceptive pill use on flavanone excretion. British Journal of Nutrition 101:5 (2009), 664–675.
8. Cerdá, B., Llorach, R., Cerón, J.J., Espín, J.C., Tomás-Barberán, F.A., Evaluation of the bioavailability and metabolism in the rat of punicalagin, and antioxidant polyphenol of pomegranate juice. European Journal of Nutrition 42 (2003), 18–28.
9. Cerdá, B., Tomás-Barberán, F.A., Espín, J.C., Metabolism of antioxidant and chemopreventive ellagitannins from strawberries, raspberries, walnuts and oak-aged wine in humans: Identification of biomarkers and individual variability. Journal of Agricultural and Food Chemistry 53:2 (2005), 227–235.
10. Chanet, A., Milenkovic, D., Claude, S., Maier, J.A., Kamran Khan, M., Rakotomanomana, N., et al. Flavanone metabolites decrease monocyte adhesion to TNF-α-activated endothelial cells by modulating expression of atherosclerosis-related genes. British Journal of Nutrition 110:4 (2013), 587–598.
11. Clavel, T., Desmarchelier, C., Haller, D., Gérard, P., Rohn, S., Lepage, P., et al. Intestinal microbiota in metabolic diseases: From bacterial community structure and function to species of pathological relevance. Gut Microbes 5:4 (2014), 544–551.
12. Dall'Asta, M., Derlindati, E., Curella, V., Mena, P., Calani, L., Ray, S., et al. Effects of naringenin and its phase II metabolites on in vitro human macrophage gene expression. International Journal of Food Sciences and Nutrition 64:7 (2013), 843–849.
13. Fernández-Millán, E., Ramos, S., Alvarez, C., Bravo, L., Goya, L., Martín, M.Á., Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against tert-butyl hydroperoxide-induced toxicity via ERKs and PKC pathways. Food Chemical Toxicology 66 (2014), 245–253.
14. García-Villalba, R., Espín, J.C., Aaby, K., Alasalvar, C., Heinonen, M., Jacobs, G., et al. Validated method for the characterization and quantification of extractable and non-extractable ellagitannins after acid hydrolysis in pomegranate fruits, juices and extracts. Journal of Agricultural and Food Chemistry 63:29 (2015), 6555–6566.
15. Giménez-Bastida, J.A., González-Sarrías, A., Larrosa, M., Tomás-Barberán, F., Espín, J.C., García-Conesa, M.T., Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. Molecular Nutrition and Food Research 56:5 (2012), 784–796.
16. Giménez-Bastida, J.A., González-Sarrías, A., Vallejo, F., Espín, J.C., Tomás-Barberán, F.A., Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels. Food Function 7:1 (2016), 118–126.
17. González-Sarrías, A., García-Villalba, R., Núñez-Sánchez, M.A., Tomé-Carneiro, J., Zafrilla, P., Mulero, J., et al. Identifying the limits of ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts. Journal of Functional Foods 19 (2015), 225–235.
18. González-Sarrías, A., García-Villalba, R., Romo-Vaquero, M., Alasalvar, C., Örem, A., Zafrilla, P., et al. Clustering according to urolithin metabotype explains the interindividual variability in the improvement of cardiovascular risk biomarkers in overweight-obese individuals consuming pomegranate: A randomised clinical trial. Molecular Nutrition and Food Research, 2017, 10.1002/mnfr.201600830.
19. González-Sarrías, A., Giménez-Bastida, J.A., Núñez-Sánchez, M.A., Larrosa, M., García-Conesa, M.T., Tomás-Barberán, F.A., et al. Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. European Journal of Nutrition 53:3 (2014), 853–864.
20. Grimm, T., Schäfer, A., Högger, P., Antioxidant activity and inhibition of matrix metalloproteinases by metabolites of maritime pine barkextract (pycnogenol). Free Radical Biology & Medicine. 36:6 (2004), 811–822.
21. Hazim, S., Curtis, P.J., Schär, M.Y., Ostertag, L.M., Kay, C.D., Minihane, A.M., et al. 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. American Journal of Clinical Nutrition 103:3 (2016), 694–702.
22. Huang, J., de Paulis, T., May, J.M., Antioxidant effects of dihydrocaffeic acid in human EA.hy926 endothelial cells. The Journal of Nutritional Biochemistry 15:12 (2004), 722–729.
23. Ishimoto, H., Shibata, M., Myojin, Y., Ito, H., Sugimoto, Y., Tai, A., et al. In vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin A. Bioorganic & Medicinal Chemistry Letters 21:19 (2011), 5901–5904.
24. Kiss, A.K., Granica, S., Stolarczyk, M., Melzig, M.F., Epigenetic modulation of mechanisms involved in inflammation: Influence of selected polyphenolic substances on histone acetylation state. Food Chemistry 131:3 (2012), 1015–1020.
25. Koeth, R.A., Wang, Z., Levison, B.C., Buffa, J.A., Org, E., Sheehy, B.T., et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine 19:5 (2013), 576–585.
26. Manach, C., Milenkovic, D., Van de Wiele, T., Rodriguez-Mateos, A., de Roos, B., Garcia-Conesa, M.T., et al. 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. Molecular Nutrition and Food Research, 2016, 10.1002/mnfr.201600557.
27. Matthews, S., Mila, I., Scalbert, A., Donnely, D.M.X., Extractable and non-extractable proanthocyanidins in barks. Phytochemistry 45:2 (1997), 405–410.
28. McKay, D.L., Chen, C.-Y.O., Zampariello, C.A., Blumberg, J.B., Flavonoids and phenolic acids from cranberry are bioavailable and bioactive in healthy older adults. Food Chemistry 168 (2015), 233–240.
29. Mele, L., Carobbio, S., Brindani, N., Curti, C., Rodriguez-Cuenca, S., Bidault, G., et al. Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function. Molecular Nutrition and Food Research, 2017, 10.1002/mnfr.201700074.
30. Mele, L., Mena, P., Piomontese, A., Marino, A., López-Gutiérrez, N., Bernini, F., et al. Antioatherogenic effects of ellagic acid and urolithins in vitro. Archives of Biochemistry and Biophysics 599 (2016), 42–50.
31. Monagas, M., Khan, N., Andrés-Lacueva, C., Urpí-Sardá, M., Vázquez-Agell, M., Lamuela-Raventós, R.M., et al. Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells. British Journal of Nutrition 102:2 (2009), 201–206.
32. Nielsen, I.L., Chee, W.S.S., Poulsen, L., Offord-Cavin, E., Rasmussen, S.E., Frederiksen, H., et al. Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: A randomized, double-blind, crossover trial. The Journal of Nutrition 136:2 (2006), 404–408.
33. Pereira-Caro, G., Borges, G., van der Hooft, J., Clifford, M.N., Del Rio, D., lean, M.E.J., et al. Orange juice polyphenols are highly bioavailable in humans. American Journal of Clinical Nutrition 100:5 (2014), 1378–1384.
34. Pérez-Jiménez, J., Diaz-Rubio, M.E., Saura-Calixto, F., Contribution of macromolecular antioxidants to dietary antioxidant capacity: A study of the Spanish mediterranean diet. Plant Foods for Human Nutrition 70:4 (2015), 365–370.
35. Piwowarski, J.P., Granica, S., Kiss, A.K., Influence of gut microbiota-derived ellagitannins' metabolites urolithins on pro-inflammatory activities of human neutrophils. Planta Medica 80:11 (2014), 887–895.
36. Qiu, Z., Zhou, B., Jin, L., Yu, H., Liu, L., Liu, Y., et al. In vitro antioxidant and antiproliferative effects of ellagic acid and its colonic metabolite, urolithins, on human bladder cancer T24 cells. Food Chemical Toxicology 59 (2013), 428–437.
37. Ridaura, V.K., Faith, J.I., Rey, F., Cheng, J., Duncan, A.E., Kau, A.L., et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341(6150), 2013, 1241214.
38. Rios, L.Y., Gonthier, M.P., Rémésy, C., Mila, I., Lapierre, C., Lazarus, S.A., et al. Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. The American Journal of Clinical Nutrition 77:4 (2003), 912–918.
39. Rizza, S., Muniyappa, R., Iantorno, M., Kim, J.A., Chen, H., Pullikotil, P., et al. Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome. The Journal of Clinical Endocrinology & Metabolism 96:5 (2011), E782–E792.
40. Roowi, S., Stalmach, A., Mullen, W., Lean, M.E.J., Eswards, C., Crozier, A., Green tea flavan-3-ols: Colonic degradation and urinary excretion of catabolites by humans. Journal of Agricultural and Food Chemistry 58:2 (2010), 1296–1304.
41. Sala, R., Mena, P., Savi, M., Brighenti, F., Crozier, A., Miragoli, M., et al. Urolithins at physiological concentrations affect the levels of pro-inflammatory cytokines and growth factor in cultured cardiac cells in hyperglucidic conditions. Journal of Functional Foods 15 (2015), 97–105.
42. Sampson, T.R., Debelius, J.W., Thron, T., Janssen, S., Shastri, G.G., Ilhan, Z.E., et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell 167:6 (2016), 1469–1480.
43. Seeram, N.P., Henning, S.M., Zhang, Y., Suchard, M., Li, Z., Heber, D., Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. The Journal of Nutrition 136:10 (2006), 2481–2485.
44. Selma, M.V., Espín, J.C., Tomás-Barberán, F.A., Interaction between phenolics and gut microbiota: Role in human health. Journal of Agricultural and Food Chemistry 57:15 (2009), 6485–6501.
45. Silveira, J.Q., Cesar, T.B., Manthey, J.A., Baldwin, E.A., Bai, J., Raithore, S., Pharmacokinetics of flavanone glycosides after ingestion of single doses of freh-squeezed orange juice versus commercially processed orange juice in healthy humans. Journal of Agricultural and Food Chemistry 62:52 (2014), 12576–12584.
46. Spigoni, V., Mena, P., Cito, M., Fantuzzi, F., Bonadonna, R.C., Brighenti, F., et al. Effects on nitric oxide production of urolithins, gut-derived ellagitannin metabolites, in human aortic endothelial cells. Molecules, 21(8), 2016, E1009.
47. Takumi, H., Nakamura, H., Simizu, T., Harada, R., Kometani, T., Nadamoto, T., et al. Bioavailability of orally administered water-dispersible hesperetin and its effect on peripheral vasodilatation in human subjects: Implication of endothelial functions of plasma conjugated metabolites. Food Function 3:4 (2012), 389–398.
48. Tomás-Barberán, F.A., Clifford, M.N., Flavanones, chalcones and dihydrochalcones - nature, occurrence and dietary burden. Journal of the Science of Food and Agriculture 80:7 (2000), 1073–1080.
49. Tomás-Barberán, F.A., Selma, M.V., Espín, J.C., Interactions of gut microbiota with dietary polyphenols and consequences to human health. Current Opinion on Clinical Nutrition and Metabolic Care 19:6 (2016), 471–476.
50. Truchado, P., Larrosa, M., García-Conesa, M.T., Cerdá, B., Vidal-Guevara, M.L., Tomás-Barberán, F.A., et al. Strawberry processing does not affect the production and urinary excretion of urolithins, ellagic acid metabolites, in humans. Journal of Agricultural and Food Chemistry 60:23 (2012), 5749–5754.
51. Urpi-Sarda, M., Garrido, I., Monagas, M., Gomez-Cordovés, C., Medina-Remón, A., Andres-Lacueva, C., et al. Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans. Journal of Agricultural and Food Chemistry 57:21 (2009), 10134–10142.
52. Vallejo, F., Larrosa, M., Escudero, E., Zafrilla, M.P., Cerdá, B., Boza, J., et al. Concentration and solubility of flavanones in orange beverages affect their bioavailability in humans. Journal of Agricultural and Food Chemistry 58:10 (2010), 6516–6524.
53. Ward, N.C., Croft, K.D., Puddey, I.B., Hodgson, J.M., Supplementation with grape seed polyphenols results in increased urinary excretion of 3-hydroxyphenylpropionic acid, and important metabolite or proanthocyanidin in humans. Journal of Agricultural and Food Chemistry 52:17 (2004), 5545–5549.
54. Whitley, A.C., Stoner, G.D., Darby, M.V., Walle, T., Intestinal epithelial cell accumulation of the cancer preventive polyphenol ellagic acid – extensive binging to proteins and DNA. Biochemical Pharmacology 66:6 (2003), 907–915.
55. Williamson, G., Clifford, M.N., Colonic metabolites of berry polyphenols: The missing link to biological activity?. British Journal of Nutrition 104:3 (2010), S48–S66.
56. Yamamoto, M., Jokura, H., Hashizume, K., Ominami, H., Shibuya, Y., Suzuki, A., et al. Hesperidin metabolite hesperetin-7-O-glucuronide, but not hesperetin-3′-O-glucuronide, exerts hypotensive, vasodilatory, and anti-inflammatory activities. Food Function 4:9 (2013), 1346–1351.
57. Yang, H.L., Chen, S.C., Senthil Kumar, K.J., Yu, K.N., Lee Chao, P.D., Tsai, S.Y., et al. Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: An ex vivo approach. Journal of Agricultural and Food Chemistry. 60:1 (2012), 522–532.
58. Yatsunenko, T., Rey, F.E., Manary, M.J., Trehan, I., Dominguez-Bello, M.G., Contreras, M., et al. Human gut microbiome viewed across age and geography. Nature 486:7402 (2012), 222–227.
59. Yu, Y.M., Wang, Z.H., Liu, C.H., Chen, C.S., Ellagic acid inhibits IL-1beta-induced cell adhesion molecule expression in human umbilical vein endothelial cells. British Journal of Nutrition 97:4 (2007), 692–698.