Prebiotic nut compounds and human microbiota

Critical Reviews in Food Science and Nutrition

Volumn 57, Issue 14, 2017, Pages 3154-3163

  Lamuel Raventos, Rosa M ^a,b   Onge, Marie Pierre St ^c  

^a UNIVERSITY OF BARCELONA   (Spain)

^b Instituto de Salud Carlos III   (Spain)

^c Columbia University ^*  (United States)

Author keywords

butyrate; fiber; Nuts; polyphenols; polysaccharides; urolithins; valerolactones

Indexed keywords

FIBERS; POLYSACCHARIDES;

BUTYRATE; NUTS; POLYPHENOLS; UROLITHINS; VALEROLACTONES;

FATTY ACIDS;

POLYPHENOL; PREBIOTIC AGENT;

ANALYSIS; CHEMISTRY; DIETARY FIBER; HUMAN; INTESTINE FLORA; NUT; NUTRITIONAL VALUE; PHYSIOLOGY;

DIETARY FIBER; GASTROINTESTINAL MICROBIOME; HUMANS; NUTRITIVE VALUE; NUTS; POLYPHENOLS; PREBIOTICS;

EID: 85019625779     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408398.2015.1096763     Document Type: Article

References (105)

1. Abe, L. T., Lajolo, F. M., and Genovese, M. I., (2010). Comparison of phenol content and antioxidant capacity of nuts. Ciência e Tecnol. Aliment. 30:254–259.
2. American Institute for Cancer Research (2015). No Title [Internet]. Available from:.
3. Appeldoorn, M. M., Vincken, J.-P., Aura, A.-M., Hollman, P. C. H., and Gruppen, H., (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. 57:1084–1092.
4. Babio, N., Toledo, E., Estruch, R., Ros, E., Martínez-González, M. A., Castañer, O., Bulló, M., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R. M., Serra-Majem, L., Pintó, X., Basora, J., Sorlí, J. V., and Salas-Salvadó, J., (2014). Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial. CMAJ. 186:E649–E657.
5. Bao, Y., Han, J., Hu, F. B., Giovannucci, E. L., Stampfer, M. J., Willett, W. C., and Fuchs, C. S., (2013). Association of nut consumption with total and cause-specific mortality. N. Engl. J. Med. 369:2001–2011.
6. Berryman, C. E., West, S. G., Fleming, J. A., Bordi, P. L., and Kris-Etherton, P. M., (2015). Effects of daily almond consumption on cardiometabolic risk and abdominal adiposity in healthy adults with elevated LDL-cholesterol:A randomized controlled trial. J. Am. Heart Assoc. 4:e000993–e000993.
7. Bittner, K., Rzeppa, S., and Humpf, H. U., (2013). Distribution and quantification of flavan-3-ols and procyanidins with low degree of polymerization in nuts, cereals, and legumes. J. Agric. Food Chem. 61:9148–9154.
8. Blaiotta, G., La Gatta, B., Di Capua, M., Di Luccia, A., Coppola, R., and Aponte, M., (2013). Effect of chestnut extract and chestnut fiber on viability of potential probiotic Lactobacillus strains under gastrointestinal tract conditions. Food Microbiol. 36:161–169.
9. Brahe, L. K., Astrup, A., and Larsen, L. H., (2013) Is butyrate the link between diet, intestinal microbiota and obesity-related metabolic diseases? Obes. Rev. 14:950–959.
10. Cardona, F., Andrés-Lacueva, C., Tulipani, S., Tinahones, F. J., and Queipo-Ortuño, M. I., (2013). Benefits of polyphenols on gut microbiota and implications in human health. J. Nutr. Biochem. 24:1415–1422.
11. Cassady, B. A., Hollis, J. H., Fulford, A. D., Considine, R. V., and Mattes, R. D., (2009). Mastication of almonds:Effects of lipid bioaccessibility, appetite, and hormone response. Am. J. Clin. Nutr. 89:794–800.
12. Cerdá, B., Soto, C., Albaladejo, M. D., Martínez, P., Sánchez-Gascón, F., Tomás-Barberán, F., and Espín, J. C., (2006). Pomegranate juice supplementation in chronic obstructive pulmonary disease:A 5-week randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Nutr. 60:245–253.
13. Cerdá, B., Tomás-Barberán, F. A., and Espín, J. C., (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.
14. Cho, H., Jung, H., Lee, H., Yi, H. C., Kwak, H.-K., and Hwang, K. T., (2015). Chemopreventive activity of ellagitannins and their derivatives from black raspberry seeds on HT-29 colon cancer cells. Food Funct. 6:1675–1683.
15. Choy, Y. Y., Jaggers, G. K., Oteiza, P. I., and Waterhouse, A. L., (2013). Bioavailability of intact proanthocyanidins in the rat colon after ingestion of grape seed extract. J. Agric. Food Chem. 61:121–127.
16. Choy, Y. Y., Quifer-Rada, P., Holstege, D. M., Frese, S. A., Calvert, C. C., Mills, D. A., Lamuela-Raventos, R. M., and Waterhouse, A. L., (2014). Phenolic metabolites and substantial microbiome changes in pig feces by ingesting grape seed proanthocyanidins. Food Funct. 5(9):2298–2308.
17. Choy, Y. Y., and Waterhouse, A. L., (2014). Proanthocyanidin Metabolism, a mini review. Nutr. Aging. 2:111–116.
18. Damasceno, N. R. T., Sala-Vila, A., Cofán, M., Pérez-Heras, A. M., Fitó, M., Ruiz-Gutiérrez, V., Martínez-González, M.-Á. Á., Corella, D., Arós, F., Estruch, R., and Ros, E., (2013). Mediterranean diet supplemented with nuts reduces waist circumference and shifts lipoprotein subfractions to a less atherogenic pattern in subjects at high cardiovascular risk. Atherosclerosis. 230:347–353.
19. Ellis, P. R., Kendall, C. W. C., Ren, Y., Parker, C., Pacy, J. F., Waldron, K. W., and Jenkins, D. J. A., (2004). Role of cell walls in the bioaccessibility of lipids in almond seeds. Am. J. Clin. Nutr. 80:604–613.
20. Espín, J. C., Larrosa, M., García-Conesa, M. T., and Tomás-Barberán, F., (2013). Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites:The evidence so far. Evid. Based. Complement. Alternat. Med. 2013:270418.
21. Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R. M., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M. A., Sorlí, J. V, Martínez, J. A., and Martínez-González, M. A., (2013). Primary prevention of cardiovascular disease with a mediterranean diet. New Engl. J. Med. 368:1279–1290.
22. Flores-Mateo, G., Rojas-Rueda, D., Basora, J., Ros, E., and Salas-Salvadó, J., (2013). Nut intake and adiposity:Meta-analysis of clinical trials. Am. J. Clin. Nutr. 97:1346–1355.
23. Frankenfeld, C. L., Cerhan, J. R., Cozen, W., Davis, S., Schenk, M., Morton, L. M., Hartge, P., and Ward, M. H., (2008). Dietary flavonoid intake and non-Hodgkin lymphoma risk. Am. J. Clin. Nutr. 87:1439–1445.
24. Freedland, S. J., Carducci, M., Kroeger, N., Partin, A., Rao, J.-Y., Jin, Y., Kerkoutian, S., Wu, H., Li, Y., Creel, P., Mundy, K., Gurganus, R., Fedor, H., King, S. A., Zhang, Y., Heber, D., and Pantuck, A. J., (2013). A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy. Cancer Prev. Res. (Phila). 6:1120–1127.
25. Garcia-Aloy, M., Llorach, R., Urpi-Sarda, M., Tulipani, S., Estruch, R., Martínez-González, M. A., Corella, D., Fitó, M., Ros, E., Salas-Salvadó, J., and Andres-Lacueva, C., (2014). Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population:The PREDIMED Study. J. Proteome Res. 13:3476–3483.
26. Garrido, I., Urpi-Sarda, M., Monagas, M., Gómez-Cordovés, C., Martín-Alvarez, P. J., Llorach, R., Bartolomé, B., and Andrés-Lacueva, C., (2010). Targeted analysis of conjugated and microbial-derived phenolic metabolites in human urine after consumption of an almond skin phenolic extract. J. Nutr. 140:1799–1807.
27. Gill, S. R., Pop, M., Deboy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., and Nelson, K. E., (2006). Metagenomic analysis of the human distal gut microbiome. Science. 312:1355–1359.
28. Giménez-Bastida, J. A., González-Sarrías, A., Larrosa, M., Tomás-Barberán, F., Espín, J. C., and García-Conesa, M.-T., (2012). Ellagitannin metabolites, urolithin A glucuronide and its aglycone urolithin A, ameliorate TNF-α-induced inflammation and associated molecular markers in human aortic endothelial cells. Mol. Nutr. Food Res. 56:784–796.
29. González-Sarrías, A., Giménez-Bastida, J. A., García-Conesa, M. T., Gómez-Sánchez, M. B., García-Talavera, N. V, Gil-Izquierdo, A., Sánchez-Alvarez, C., Fontana-Compiano, L. O., Morga-Egea, J. P., Pastor-Quirante, F. A., Martínez-Díaz, F., Tomás-Barberán, F. A., and Espín, J. C., (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. 54:311–322.
30. González-Sarrías, A., Giménez-Bastida, J. A., Núñez-Sánchez, M. Á., Larrosa, M., García-Conesa, M. T., Tomás-Barberán, F. A., and Espín, J. C., (2014). Phase-II metabolism limits the antiproliferative activity of urolithins in human colon cancer cells. Eur. J. Nutr. 53:853–864.
31. González-Sarrías, A., Tomé-Carneiro, J., Bellesia, A., Tomás-Barberán, F. A., and Espín, J. C., (2015). The ellagic acid-derived gut microbiota metabolite, urolithin A, potentiates the anticancer effects of 5-fluorouracil chemotherapy on human colon cancer cells. Food Funct. 6:1460–1469.
32. Grassby, T., Picout, D. R., Mandalari, G., Faulks, R. M., Kendall, C. W. C., Rich, G. T., Wickham, M. S. J., Lapsley, K., and Ellis, P. R., (2014). Modelling of nutrient bioaccessibility in almond seeds based on the fracture properties of their cell walls. Food Funct. 5:3096–3106.
33. Grosso, G., Yang, J., Marventano, S., Micek, A., Galvano, F., and Kales, S. N., (2015). Nut consumption on all-cause, cardiovascular, and cancer mortality risk:A systematic review and meta-analysis of epidemiologic studies. Am. J. Clin. Nutr. 101:783–793.
34. Grundy, M. M. L., Grassby, T., Mandalari, G., Waldron, K. W., Butterworth, P. J., Berry, S. E. E., and Ellis, P. R., (2015). Effect of mastication on lipid bioaccessibility of almonds in a randomized human study and its implications for digestion kinetics, metabolizable energy, and postprandial lipemia. Am. J. Clin. Nutr. 101:25–33.
35. Hardman, W. E., (2014). Walnuts have potential for cancer prevention and treatment in mice. J. Nutr. 144:p.555S–560S.
36. Hartstra, A. V., Bouter, K. E. C., Backhed, F., and Nieuwdorp, M., (2014). Insights into the role of the microbiome in obesity and Type 2 diabetes. Diabetes Care. 38:159–165.
37. Holt, R. R., Heiss, C., Kelm, M., and Keen, C. L., (2012). The potential of flavanol and procyanidin intake to influence age-related vascular disease. J. Nutr. Gerontol. Geriatr. 31:290–323.
38. Kaji, I., Karaki, S., and Kuwahara, A., (2014). Short-chain fatty acid receptor and its contribution to glucagon-like peptide-1 release. Digestion. 89:31–36.
39. Kamijo, M., Kanazawa, T., Funaki, M., Nishizawa, M., and Yamagishi, T., (2008). Effects of Rosa rugosa petals on intestinal bacteria. Biosci. Biotechnol. Biochem. 72:773–777.
40. Kim, H., Yokoyama, W., and Davis, P. A., (2014). TRAMP prostate tumor growth is slowed by walnut diets through altered IGF-1 levels, energy pathways, and cholesterol metabolism. J. Med. Food. 17:1281–1286.
41. Kutschera, M., Engst, W., Blaut, M., and Braune, A., (2011). Isolation of catechin-converting human intestinal bacteria. J. Appl. Microbiol. 111:165–175.
42. Leonel, A. J., and Alvarez-Leite, J. I., (2012). Butyrate:Implications for intestinal function. Curr. Opin. Clin. Nutr. Metab. Care. 15:474–479.
43. Li, Z., Summanen, P. H., Komoriya, T., Henning, S. M., Lee, R.-P., Carlson, E., Heber, D., and Finegold, S. M., (2015). Pomegranate ellagitannins stimulate growth of gut bacteria in vitro:Implications for prebiotic and metabolic effects. Anaerobe. 34:164–168.
44. Liu, Z., Lin, X., Huang, G., Zhang, W., Rao, P., and Ni, L., (2014). Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans. Anaerobe. 26:1–6.
45. Llorach, R., Garrido, I., Monagas, M. M., Urpi-Sarda, M., Tulipani, S., Bartolome, B. B., and Andres-Lacueva, C., (2010). Metabolomics study of human urinary metabolome modifications after intake of almond (Prunus dulcis (Mill.) D.A. Webb) skin polyphenols. J. Proteome Res. 9:5859–5867.
46. Mandalari, G., Faulks, R. M., Bisignano, C., Waldron, K. W., Narbad, A., and Wickham, M. S. J., (2010). In vitro evaluation of the prebiotic properties of almond skins (Amygdalus communis L.). FEMS Microbiol. Lett. 304:116–122.
47. Mandalari, G., Grundy, M. M.-L., Grassby, T., Parker, M. L., Cross, K. L., Chessa, S., Bisignano, C., Barreca, D., Bellocco, E., Laganà, G., Butterworth, P. J., Faulks, R. M., Wilde, P. J., Ellis, P. R., and Waldron, K. W., (2014). The effects of processing and mastication on almond lipid bioaccessibility using novel methods of in vitro digestion modelling and micro-structural analysis. Br. J. Nutr. 112:1521–1529.
48. Mandalari, G., Nueno-Palop, C., Bisignano, G., Wickham, M. S. J., and Narbad, A., (2008). Potential prebiotic properties of almond (Amygdalus communis L.) seeds. Appl. Environ. Microbiol. 74:4264–4270.
49. Mandalari, G., Tomaino, A., Rich, G.T., Lo Curto, R., Arcoraci, T., Martorana, M., Bisignano, C., Saija, A., Parker, M. L., Waldron, K. W., and Wickham, M. S. J., (2010). Polyphenol and nutrient release from skin of almonds during simulated human digestion. Food Chem. 122:1083–1088.
50. McCullough, M. L., Peterson, J. J., Patel, R., Jacques, P. F., Shah, R., and Dwyer, J. T., (2012). Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am. J. Clin. Nutr. 95:454–464.
51. Mülek, M., Fekete, A., Wiest, J., Holzgrabe, U., Mueller, M. J., and Högger, P., (2015). Profiling a gut microbiota-generated catechin metabolite's fate in human blood cells using a metabolomic approach. J. Pharm. Biomed. Anal. 114:71–81.
52. Mülek, M., and Högger, 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. 407:1885–1899.
53. Nielsen, S. J., Ph, D., Div, M., Kit, B. K., Ogden, C. L., and Ph, D., (2014). Nut Consumption Among U.S. Adults. 2009–2010.
54. Novotny, J. A., Gebauer, S. K., and Baer, D. J., (2012). Discrepancy between the Atwater factor predicted and empirically measured energy values of almonds in human diets. Am. J. Clin. Nutr. 96:296–301.
55. Nuñez-Sánchez, M. A., García-Villalba, R., Monedero-Saiz, T., García-Talavera, N. V, Gómez-Sánchez, M. B., Sánchez-Álvarez, C., García-Albert, A. M., Rodríguez-Gil, F. J., Ruiz-Marín, M., Pastor-Quirante, F. A., Martínez-Díaz, F., Yáñez-Gascón, M. J., González-Sarrías, A., Tomás-Barberán, F. A., and Espín, J. C., (2014). Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients. Mol. Nutr. Food Res. 58:1199–1211.
56. Ottaviani, J. I., Kwik-Uribe, C., Keen, C. L., and Schroeter, H., (2012). Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am. J. Clin. Nutr. 95:851–858.
57. Ou, K., Sarnoski, P., Schneider, K. R., Song, K., Khoo, C., and Gu, L., (2014). Microbial catabolism of procyanidins by human gut microbiota. Mol. Nutr. Food Res. 58:2196–2205.
58. Pérez-Jiménez, J., Neveu, V., Vos, F., and Scalbert, A., (2010). Identification of the 100 richest dietary sources of polyphenols:An application of the Phenol-Explorer database. Eur. J. Clin. Nutr. 64(Suppl 3):S112–S120.
59. Pfundstein, B., Haubner, R., Würtele, G., Gehres, N., Ulrich, C. M., and Owen, R. W., (2014). Pilot walnut intervention study of urolithin bioavailability in human volunteers. J. Agric. Food Chem. 62:10264–10273.
60. Phillips, G. O., and Cui, S. W., (2011). An introduction:Evolution and finalisation of the regulatory definition of dietary fibre. Food Hydrocoll. 25:139–143.
61. Piwowarski, J. P., Granica, S., and Kiss, A. K., (2014). Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils. Planta Med. 80:887–895.
62. Piwowarski, J.P., Granica, S., Zwierzyńska, M., Stefańska, J., Schopohl, P., Melzig, M. F., and Kiss, A. K., (2014). Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials. J. Ethnopharmacol. 155:801–809.
63. Puertollano, E., Kolida, S., and Yaqoob, P., (2014). Biological significance of short-chain fatty acid metabolism by the intestinal microbiome. Curr. Opin. Clin. Nutr. Metab. Care. 17:139–144.
64. Puupponen-Pimiä, R., Seppänen-Laakso, T., Kankainen, M., Maukonen, J., Törrönen, R., Kolehmainen, M., Leppänen, T., Moilanen, E., Nohynek, L., Aura, A.-M., Poutanen, K., Tómas-Barberán, F. A., Espín, J. C., and Oksman-Caldentey, K.-M., (2013). Effects of ellagitannin-rich berries on blood lipids, gut microbiota, and urolithin production in human subjects with symptoms of metabolic syndrome. Mol. Nutr. Food Res. 57:2258–2263.
65. Rajaram, S., and Sabaté, J., (2006). Nuts, body weight and insulin resistance. Br. J. Nutr. 96(Suppl 2):S79–S86.
66. Ramírez de Molina, A., Vargas, T., Molina, S., Sánchez, J., Martínez-Romero, J., González-Vallinas, M., Martín-Hernández, R., Sánchez-Martínez, R., Gómez de Cedrón, M., Dávalos, A., Calani, L., Del Rio, D., González-Sarrías, A., Espín, J. C., Tomás-Barberán, F. A., and Reglero, G., (2015). The ellagic acid derivative 4,4’-di-O-methylellagic acid efficiently inhibits colon cancer cell growth through a mechanism involving WNT16. J. Pharmacol. Exp. Ther. 353:433–444.
67. Regueiro, J., Sánchez-González, C., Vallverdú-Queralt, A., Simal-Gándara, J., Lamuela-Raventós, R., and Izquierdo-Pulido, M., (2014). Comprehensive identification of walnut polyphenols by liquid chromatography coupled to linear ion trap-Orbitrap mass spectrometry. Food Chem. 152:340–348.
68. Reiter, R. J., Tan, D.-X., Manchester, L. C., Korkmaz, A., Fuentes-Broto, L., Hardman, W. E., Rosales-Corral, S. A., and Qi, W., (2013). A walnut-enriched diet reduces the growth of LNCaP human prostate cancer xenografts in nude mice. Cancer Invest. 31:365–373.
69. Rhodes, L. E., Darby, G., Massey, K. A., Clarke, K. A., Dew, T. P., Farrar, M. D., Bennett, S., Watson, R. E. B., Williamson, G., and Nicolaou, A., (2013). Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid. Br. J. Nutr. 110:891–900.
70. Roberfroid, M., (2007). Prebiotics:The Concept Revisited. J. Nutr. 137:830S–837.
71. Roberfroid, M., Gibson, G.R., Hoyles, L., McCartney, A.L., Rastall, R., Rowland, I., Wolvers, D., Watzl, B., Szajewska, H., Stahl, B., Guarner, F., Respondek, F., Whelan, K., Coxam, V., Davicco, M.-J., Léotoing, L., Wittrant, Y., Delzenne, N.M., Cani, P.D., Neyrinck, A.M., and Meheust, A., (2010). Prebiotic effects:Metabolic and health benefits. Br. J. Nutr. 104(Suppl):S1–S63.
72. Rodriguez-Mateos, A., Cifuentes-Gomez, T., Gonzalez-Salvador, I., Ottaviani, J. I., Schroeter, H., Kelm, M., Heiss, C., and Spencer, J. P. E., (2015). Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Mol. Nutr. Food Res.
73. Rossi, M., Edefonti, V., Parpinel, M., Lagiou, P., Franchi, M., Ferraroni, M., Decarli, A., Zucchetto, A., Serraino, D., Dal Maso, L., Negri, E., and La Vecchia, C., (2013). Proanthocyanidins and other flavonoids in relation to endometrial cancer risk:A case-control study in Italy. Br. J. Cancer 109:1914–1920.
74. Rossi, M., Lugo, A., Lagiou, P., Zucchetto, A., Polesel, J., Serraino, D., Negri, E., Trichopoulos, D., and La Vecchia, C., (2012) Proanthocyanidins and other flavonoids in relation to pancreatic cancer:A case-control study in Italy. Ann. Oncol. 23:1488–1493.
75. Rossi, M., Negri, E., Parpinel, M., Lagiou, P., Bosetti, C., Talamini, R., Montella, M., Giacosa, A., Franceschi, S., and La Vecchia, C., (2010) Proanthocyanidins and the risk of colorectal cancer in Italy. Cancer Causes Control. 21:243–250.
76. Salas-Salvadó, J., Bulló, M., Estruch, R., Ros, E., Covas, M.-I., Ibarrola-Jurado, N., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Romaguera, D., Lapetra, J., Lamuela-Raventós, R. M., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M. A., Sorlí, J. V, and Martínez-González, M. A., (2014). Prevention of diabetes with Mediterranean diets:A subgroup analysis of a randomized trial. Ann. Intern. Med. 160:1–10.
77. Salas-Salvadó, J., Bulló, M., Pérez-Heras, A., and Ros, E., (2006). Dietary fibre, nuts and cardiovascular diseases. Br. J. Nutr. 96(Suppl 2):S46–S51.
78. Salas-Salvadó, J., Fernández-Ballart, J., Ros, E., Martínez-González, M.-A., Fitó, M., Estruch, R., Corella, D., Fiol, M., Gómez-Gracia, E., Arós, F., Flores, G., Lapetra, J., Lamuela-Raventós, R., Ruiz-Gutiérrez, V., Bulló, M., Basora, J., and Covas, M.-I., (2008). Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status:One-year results of the PREDIMED randomized trial. Arch. Intern. Med. 168:2449–2458.
79. Sánchez-González, C., Ciudad, C. J., Izquierdo-Pulido, M., and Noé, V., (2016). Urolithin A causes p21 up-regulation in prostate cancer cells. Eur. J. Nutr. 55:1099–1112.
80. Sánchez-González, C., Ciudad, C. J., Noé, V., and Izquierdo-Pulido, M., (2014). Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells. Food Funct. 5:2922–2930.
81. Saura-Calixto, F., (2012). Concept and health-related properties of nonextractable polyphenols:The missing dietary polyphenols. J. Agric. Food Chem. 60:11195–11200.
82. Seeram, N. P., Henning, S. M., Zhang, Y., Suchard, M., Li, Z., and Heber, D., (2006). Pomegranate juice ellagitannin metabolites are present in human plasma and some persist in urine for up to 48 hours. J. Nutr. 136:2481–2485.
83. Selma, M. V, Espín, J. C., and Tomás-Barberán, F. A., (2009). Interaction between phenolics and gut microbiota:Role in human health. J. Agric. Food Chem. 57:6485–6501.
84. Shen, W., Gaskins, H. R., and McIntosh, M. K., (2014). Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J. Nutr. Biochem. 25:270–80. Available from:[Accessed 18 August 2015].
85. Simon, J. A., Tanzman, J. S., and Sabaté, J., (2007). Lack of effect of walnuts on serum levels of prostate specific antigen:A brief report. J. Am. Coll. Nutr. 26:317–20.
86. Slavin, J., (2013). Fiber and prebiotics:Mechanisms and health benefits. Nutrients 5:1417–1435.
87. Spaccarotella, K. J., Kris-Etherton, P. M., Stone, W. L., Bagshaw, D. M., Fishell, V. K., West, S. G., Lawrence, F. R., and Hartman, T. J., (2008). The effect of walnut intake on factors related to prostate and vascular health in older men. Nutr. J. 7:13.
88. St-Onge, M. P., Farnworth, E. R., and Jones, P. J. H., (2000). Consumption of fermented and nonfermented dairy products:Effects on cholesterol concentrations and metabolism. Am. J. Clin. Nutr. 71:674–681.
89. Takagaki, A., and Nanjo, F., (2015). Bioconversion of (−)-epicatechin, (+)-epicatechin, (−)-catechin, and (+)-catechin by (−)-epigallocatechin-metabolizing bacteria. Biol. Pharm. Bull. 38:789–794.
90. Tan, S. Y., Dhillon, J., and Mattes, R. D., (2014). A review of the effects of nuts on appetite, food intake, metabolism, and body weight. Am. J. Clin. Nutr. 100(Suppl 1):412S–422S.
91. Thompson, C. A., Habermann, T. M., Wang, A. H., Vierkant, R. A., Folsom, A. R., Ross, J. A., and Cerhan, J. R., (2010). Antioxidant intake from fruits, vegetables and other sources and risk of non-Hodgkin's lymphoma:The Iowa Women's Health Study. Int. J. Cancer. 126:992–1003.
92. Tomás-Barberán, F. A., García-Villalba, R., González-Sarrías, A., Selma, M. V, and Espín, J.C., (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. 62:6535–6538.
93. Tulipani, S., Llorach, R., Jáuregui, O., López-Uriarte, P., Garcia-Aloy, M., Bullo, M., Salas-Salvadó, J., and Andrés-Lacueva, C., (2011). Metabolomics unveils urinary changes in subjects with metabolic syndrome following 12-week nut consumption. J. Proteome Res. 10:5047–5058.
94. Tulipani, S., Urpi-Sarda, M., García-Villalba, R., Rabassa, M., López-Uriarte, P., Bulló, M., Jáuregui, O., Tomás-Barberán, F., Salas-Salvadó, J., Espín, J. C., and Andrés-Lacueva, C., (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. 60:8930–8940.
95. Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., and Gordon, J. I., (2007). The human microbiome project. Nature. 449:804–810.
96. Tzounis, X., Rodriguez-Mateos, A., Vulevic, J., Gibson, G. R., Kwik-Uribe, C., and Spencer, J. P. E., (2011). Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am. J. Clin. Nutr. 93:62–72.
97. Ukhanova, M., Wang, X., Baer, D. J., Novotny, J. A., Fredborg, M., and Mai, V., (2014). Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study. Br. J. Nutr. 111:2146–2152.
98. Urpi-Sarda, M., Garrido, I., Monagas, M., Gómez-Cordovés, C., Medina-Remón, A., Andres-Lacueva, C., and Bartolomé, B., (2009). Profile of plasma and urine metabolites after the intake of almond [Prunus dulcis (Mill.) D.A. Webb] polyphenols in humans. J. Agric. Food Chem. 57:10134–10142.
99. USDA Scientific Report of the 2015 Dietary Guidelines Advisory Committee.
100. Van den Brandt, P.A., and Schouten, L. J., (2015). Relationship of tree nut, peanut and peanut butter intake with total and cause-specific mortality:A cohort study and meta-analysis. Int. J. Epidemiol. 44:1038–1049.
101. Wang, X., Ouyang, Y. Y., Liu, J., and Zhao, G., (2014). Flavonoid intake and risk of CVD:A systematic review and meta-analysis of prospective cohort studies. Br. J. Nutr. 111:1–11.
102. Yamakoshi, J., Tokutake, S., Kikuchi, M., Kubota, Y., Konishi, H., and Mitsuoka, T., (2001). Effect of Proanthocyanidin-Rich Extract from Grape Seeds on Human Fecal Flora and Fecal Odor. Microb. Ecol. Health Dis. 13:25–31. Available from:[Accessed 18 June 2015].
103. Yang, J., and Rose, D. J., (2014). Long-term dietary pattern of fecal donor correlates with butyrate production and markers of protein fermentation during in vitro fecal fermentation. Nutr. Res. 34:749–759.
104. Zamora-Ros, R., Forouhi, N. G., Sharp, S. J., González, C. A., Buijsse, B., Guevara, M., van der Schouw, Y. T., Amiano, P., Boeing, H., Bredsdorff, L., Fagherazzi, G., Feskens, E. J., Franks, P. W., Grioni, S., Katzke, V., Key, T. J., Khaw, K.-T., Kühn, T., Masala, G., Mattiello, A., Molina-Montes, E., Nilsson, P. M., Overvad, K., Perquier, F., Redondo, M. L., Ricceri, F., Rolandsson, O., Romieu, I., Roswall, N., Scalbert, A., Schulze, M., Slimani, N., Spijkerman, A. M. W., Tjonneland, A., Tormo, M. J., Touillaud, M., Tumino, R., van der A, D. L., van Woudenbergh, G. J., Langenberg, C., Riboli, E., and Wareham, N. J., (2014). Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J. Nutr. 144:335–343.
105. Zhang, Y.-J., Li, S., Gan, R.-Y., Zhou, T., Xu, D.-P., and Li, H.-B., (2015). Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 16:7493–7519.