Skip to main content

New players in the relationship between diet and microbiota: the role of macromolecular antioxidant polyphenols

European Journal of Nutrition volume 60, pages 1403–1413 (2021)Cite this article

Abstract

Purpose

Solid evidence has emerged supporting the role of polyphenols and fibers as gut microbiota modulators. These studies have been limited to the data available in food composition databases, which did not include the food content of non-extractable polyphenols (NEPP). The main objective of this work is to quantify the intake of the different types of dietary polyphenols including NEPP and to evaluate their impact on the composition and activity of the intestinal microbiota.

Methods

Cross-sectional descriptive study conducted on a sample of 147 adults with no declared pathologies. Dietary intake has been registered by a semi-quantitative Food Frequency Questionnaire (FFQ) and transformed into extractable (EPP) and NEPP, and dietary fibers based on available databases. Major phylogenetic types of the intestinal microbiota were determined by qPCR and fecal SCFA quantification was performed by gas chromatography.

Results

NEPP account for two-thirds of the total polyphenols intake. A combined analysis by stepwise regression model including all dietary fiber and (poly)phenols has identified hydrolysable (poly)phenol (HPP) intake, as the best predictor of Bacteroides–Prevotella–Porphyromonas group and Bifidobacterium levels in feces. Also, HPPs were positively associated with butyric acid, while insoluble fiber was identified as a predictor of propionic acid in feces.

Conclusion

The intake of macromolecular (poly)phenols could contribute to modulate the gut microbiota by increasing the levels of certain intestinal microorganisms with proven health benefits.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Tressera-Rimbau A, Arranz S, Eder M, Vallverdú-Queralt A (2017) Dietary polyphenols in the prevention of stroke. Oxid Med Cell Longev 7:467–962. https://doi.org/10.1155/2017/7467962

    Article  CAS  Google Scholar 

  2. Lamuela-Raventos RM, Quifer-Rada P (2016) Effect of dietary polyphenols on cardiovascular risk. Heart 102:1340–1341. https://doi.org/10.1136/heartjnl-2016-309647

    Article  PubMed  Google Scholar 

  3. Vetrani C, Vitale M, Bozzetto L, Della Pepa G, Cocozza S, Costabile G, Mangione A, Cipriano P, Annuzzi G, Rivellese AA (2017) Association between different dietary polyphenol subclasses and the improvement in cardiometabolic risk factors: evidence from a randomized controlled clinical trial. Acta Diabetol 55:149–153. https://doi.org/10.1007/s00592-017-1075-x

    Article  CAS  PubMed  Google Scholar 

  4. Murillo AG, Fernández ML (2017) The relevance of dietary polyphenols in cardiovascular protection. Curr Pharm Des 23:2444–2452. https://doi.org/10.2174/1381612823666170329144307

    Article  CAS  PubMed  Google Scholar 

  5. Arab H, Mahjoub S, Hajian-Tilaki K, Moghadasi M (2016) The effect of green tea consumption on oxidative stress markers and cognitive function in patients with Alzheimer’s disease: a prospective intervention study. Casp J Intern Med 7:188–194

    Google Scholar 

  6. Magalingam KB, Radhakrishnan AK, Haleagrahara N (2015) Protective mechanisms of flavonoids in Parkinson’s disease. Oxid Med Cell Longev 2015:314560. https://doi.org/10.1155/2015/314560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mandel SA, Amit T, Weinreb O, Youdim MBH (2011) Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimer’s Dis 25:187–208. https://doi.org/10.3233/JAD-2011-101803

    Article  CAS  Google Scholar 

  8. Calabrese V, Perluigi M, Cornelius C, Coccia R, Di Domenico F, Pennisi G, Cini C, Dinkova-Kostova AT (2009) Phenolics in aging and neurodegenerative disorders. In: Fraga CG (ed) Plant phenolics and human health: biochemistry, nutrition, and pharmacology. Wiley, New York, pp 427–451

    Chapter  Google Scholar 

  9. Miranda J, Lasa A, Aguirre L, Fernández-Quintela A, Milton I, Portillo MP (2015) Potential application of non-flavonoid phenolics in diabetes: antiinflammatory effects. Curr Med Chem 22:112–131

    Article  CAS  PubMed  Google Scholar 

  10. Xiao JB, Högger P (2015) Dietary polyphenols and type 2 diabetes: current insights and future perspectives. Curr Med Chem 22:23–38

    Article  PubMed  Google Scholar 

  11. Guasch-Ferré M, Merino J, Sun Q, Fitó M, Salas-Salvadó J (2017) Dietary polyphenols, mediterranean diet, prediabetes, and type 2 diabetes: a narrative review of the evidence. Oxid Med Cell Longev 2017:6723931. https://doi.org/10.1155/2017/6723931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rocha DMUP, Caldas APS, da Silva BP, Hermsdorff HHM, Alfenas RCG (2019) Effects of blueberry and cranberry consumption on type 2 diabetes glycemic control: a systematic review. Crit Rev Food Sci Nutr 59:1816–1828. https://doi.org/10.1080/10408398.2018.1430019

    Article  CAS  PubMed  Google Scholar 

  13. Tangney CC, Rasmussen HE (2013) Polyphenols, inflammation, and cardiovascular disease. Curr Atheroscler Rep 15:324. https://doi.org/10.1007/s11883-013-0324-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shay J, Elbaz HA, Lee I, Zielske SP, Malek MH, Hüttemann M (2015) Molecular mechanisms and therapeutic effects of (-)-epicatechin and other polyphenols in cancer, inflammation, diabetes, and neurodegeneration. Oxid Med Cell Longev 2015:181260. https://doi.org/10.1155/2015/181260

    Article  PubMed  PubMed Central  Google Scholar 

  15. 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 18:1818–1892. https://doi.org/10.1089/ars.2012.4581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Scalbert A, Manach C, Morand C, Remesy C, Jimenez L (2005) Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr 45:287–306

    Article  CAS  PubMed  Google Scholar 

  17. Cuervo A, Valdés L (2014) Pilot study of diet and microbiota: interactive associations of fibers and polyphenols with human intestinal bacteria. J Agric Food Chem 62:5330–5336. https://doi.org/10.1021/jf501546a

    Article  CAS  PubMed  Google Scholar 

  18. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI (2013) Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem 24:1415–1422. https://doi.org/10.1016/j.jnutbio.2013.05.001

    Article  CAS  PubMed  Google Scholar 

  19. Selma MV, Espín JC, Tomás-Barberán FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57:6485–6501. https://doi.org/10.1021/jf902107d

    Article  CAS  PubMed  Google Scholar 

  20. Clifford MN (2004) Diet-derived phenols in plasma and tissues and their implication for health. Planta Med 70:1103–1114

    Article  CAS  PubMed  Google Scholar 

  21. Pérez-Jiménez J, Saura-Calixto F (2015) Macromolecular antioxidants or non-extractable polyphenols in fruit and vegetables: intake in four european countries. Food Res Int 74:315–323. https://doi.org/10.1016/j.foodres.2015.05.007

    Article  CAS  PubMed  Google Scholar 

  22. Arranz S, Silván JM, Saura-Calixto F (2010) Nonextractable polyphenols, usually ignored, are the major part of dietary polyphenols: a study on the Spanish diet. Mol Nutr Food Res 54:1646–1658. https://doi.org/10.1002/mnfr.200900580

    Article  CAS  PubMed  Google Scholar 

  23. Pérez-Jiménez J, Díaz-Rubio ME, Saura-Calixto F (2013) Non-extractable polyphenols, a major dietary antioxidant: occurrence, metabolic fate and health effects. Nutr Res Rev 26:118–129. https://doi.org/10.1017/S0954422413000097

    Article  CAS  PubMed  Google Scholar 

  24. Neveu V, Pérez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, Knox C, Eisner R, Cruz J, Wishart D, Scalbert A (2010) Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford) 20:024. https://doi.org/10.1093/database/bap024

    Article  CAS  Google Scholar 

  25. Bhagwat S, Haytowitz DB, Wasswa-Kintu SI, Pehrsson PR (2015) Process of formulating USDA's expanded flavonoid database for the assessment of dietary intakes: a new tool for epidemiological research. Br J Nutr 114:472–480. https://doi.org/10.1017/S0007114515001580

    Article  CAS  PubMed  Google Scholar 

  26. Saura-Calixto F, Serrano J, Goñi I (2007) Intake and bioaccessibility of total polyphenols in a whole diet. Food Chem 101:492–501. https://doi.org/10.1016/j.foodchem.2006.02.006

    Article  CAS  Google Scholar 

  27. Edwards CA, Havlik J, Cong W, Mullen W, Preston T, Morrison DJ, Combet E (2017) Polyphenols and health: interactions between fibre, plant polyphenols and the gut microbiota. Nutr Bull 42:356–360. https://doi.org/10.1111/nbu.12296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Russell W, Duthie G (2011) Influences of food constituents on gut health plant secondary metabolites and gut health: the case for phenolic acids. Proc Nutr Soc 70:389–396. https://doi.org/10.1017/S0029665111000152

    Article  CAS  PubMed  Google Scholar 

  29. de Enseñanza C, de Nutrición S (2008) Tablas de Composición de Alimentos por Medidas Caseras de Consumo Habitual en España. McGraw-Hill, Barcelona

    Google Scholar 

  30. Marlett JA, Cheung TF (1997) Database and quick methods of assessing typical dietary fiber intakes using data for 228 commonly consumed foods. J Am Diet Assoc 97:1139–1151. https://doi.org/10.1016/S0002-8223(97)00275-7

    Article  CAS  PubMed  Google Scholar 

  31. Apak R, Güçlü K, Ozyürek M, Karademir SE, Altun M (2005) Total antioxidant capacity assay of human serum using copper(II)-neocuproine as chromogenic oxidant: the CUPRAC method. Free Radic Res 39:949–961. https://doi.org/10.1080/10715760500210145

    Article  CAS  PubMed  Google Scholar 

  32. Gérard-Monnier D, Erdelmeier I, Régnard K, Moze-Henry N, Yadan JC, Chaudière J (1998) Reactions of 1-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Analytical applications to a colorimetric assay of lipid peroxidation. Chem Res Toxicol 11:1176–1183. https://doi.org/10.1021/tx9701790

    Article  PubMed  Google Scholar 

  33. Salazar N, López P, Valdés L, Margolles A, Suárez A (2013) Microbial targets for the development of functional foods accordingly with nutritional and immune parameters altered in the elderly. J Am Coll Nutr 32:399–406. https://doi.org/10.1080/07315724.2013.827047

    Article  CAS  PubMed  Google Scholar 

  34. Arboleya S, Binetti A, Salazar N, Fernández N, Solis G (2012) Establishment and development of intestinal microbiota in preterm neonates. FEMS Microbiol Ecol 79:763–772. https://doi.org/10.1111/j.1574-6941.2011.01261.x

    Article  CAS  PubMed  Google Scholar 

  35. Salazar N, Gueimonde M, Hernández-Barranco AM (2008) Exopolysaccharides produced by intestinal Bifidobacterium strains act as fermentable substrates for human intestinal bacteria. Appl Environ Microbiol 74:4737–4745. https://doi.org/10.1128/AEM.00325-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fraga CG, Croft KD, Kennedy DO, Tomás-Barberán FA (2019) The effects of polyphenols and other bioactives on human health. Food Funct 10:514–528. https://doi.org/10.1039/c8fo01997e

    Article  CAS  PubMed  Google Scholar 

  37. Wiciński M, Gębalski J, Mazurek E, Podhorecka M, Śniegocki M, Szychta P, Sawicka E, Malinowski B (2020) The influence of polyphenol compounds on human gastrointestinal tract microbiota. Nutrients 12:350. https://doi.org/10.3390/nu12020350

    Article  CAS  PubMed Central  Google Scholar 

  38. Gutiérrez-Díaz I, Fernández-Navarro T, Sánchez B, Margolles A, González S (2016) Mediterranean diet and faecal microbiota: a transversal study. Food Funct 7:2347–2356. https://doi.org/10.1039/c6fo00105j

    Article  PubMed  Google Scholar 

  39. Fernández-Navarro T, Salazar N, Gutiérrez-Díaz I, Sánchez B (2018) Bioactive compounds from regular diet and faecal microbial metabolites. Eur J Nutr 57:487–497. https://doi.org/10.1007/s00394-016-1332-8

    Article  CAS  PubMed  Google Scholar 

  40. Ludwig IA, Rubió L, Mosele JI, Motilva MJ (2018) Metabolic Fate of Extractable and Non-extractable Polyphenols. In: Saura-Calixto F, Pérez-Jiménez J (eds) Non-extractable polyphenols and carotenoids: importance in human nutrition and health. Royal Society of Chemistry, London, pp 220–240

    Chapter  Google Scholar 

  41. Goñi I, Hernández-Galiot A (2019) Intake of nutrient and non-nutrient dietary antioxidants Contribution of macromolecular antioxidant polyphenols in an elderly mediterranean population. Nutrients 11:2165. https://doi.org/10.3390/nu11092165

    Article  CAS  PubMed Central  Google Scholar 

  42. Hervert-Hernández D, García OP, Rosado JL, Goñi I (2011) The contribution of fruits and vegetables to dietary intake of polyphenols and antioxidant capacity in a Mexican rural diet: importance of fruit and vegetable variety. Food Res Int 44:1182–1189. https://doi.org/10.1016/j.foodres.2010.09.021

    Article  CAS  Google Scholar 

  43. Renard CMGC, Watrelot AA, Le Bourvellec C (2017) Interactions between polyphenols and polysaccharides: Mechanisms and consequences in food processing and digestion. Trends Food Sci Technol 60:43–51. https://doi.org/10.1016/j.tifs.2016.10.022

    Article  CAS  Google Scholar 

  44. Tomás-Barberán FA, Selma MV, Espín JC (2016) Interactions of gut microbiota with dietary polyphenols and consequences to human health. Curr Opin Clin Nutr Metab Care 19:471–476. https://doi.org/10.1097/MCO.0000000000000314

    Article  CAS  PubMed  Google Scholar 

  45. Jeffery IB, O’Toole PW (2013) Diet-microbiota interactions and their implications for healthy living. Nutrients 5:234–252. https://doi.org/10.3390/nu5010234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, Sinha R, Gilroy E, Gupta K, Baldassano R, Nessel L, Li H, Bushman FD, Lewis JD (2011) Linking long-term dietary patterns with gut microbial enterotypes. Science 334:105–108. https://doi.org/10.1126/science.1208344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Etxeberria U, Fernández-Quintela A, Milagro FI, Aguirre L, Martínez JA, Portillo MP (2013) Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition. J Agric Food Chem 61:9517–9533. https://doi.org/10.1021/jf402506c

    Article  CAS  PubMed  Google Scholar 

  48. Vitaglione P, Mennella I, Ferracane R, Rivellese AA, Giacco R, Ercolini D, Gibbons SM, La Storia A, Gilbert JA, Jonnalagadda S, Thielecke F, Gallo MA, Scalfi L, Fogliano V (2015) Whole-grain wheat consumption reduces inflammation in a randomized controlled trial on overweight and obese subjects with unhealthy dietary and lifestyle behaviors: role of polyphenols bound to cereal dietary fiber. Am J Clin Nutr 101:251–261. https://doi.org/10.3945/ajcn.114.088120

    Article  CAS  PubMed  Google Scholar 

  49. Tzounis X, Vulevic J, Kuhnle GGC, George T, Leonczak J, Gibson GR, Kwik-Uribe C, Spencer JPE (2008) Flavanol monomer-induced changes to the human faecal microflora. Br J Nutr 99:782–792. https://doi.org/10.1017/S0007114507853384

    Article  CAS  PubMed  Google Scholar 

  50. Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L (2016) Bifidobacteria and butyrate-producing colon bacteria: Importance and strategies for their stimulation in the human gut. Front Microbiol 7:979. https://doi.org/10.3389/fmicb.2016.00979

    Article  PubMed  PubMed Central  Google Scholar 

  51. Rios-Covian D, Gueimonde M, Duncan SH (2015) Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett 362:176. https://doi.org/10.1093/femsle/fnv176

    Article  CAS  Google Scholar 

  52. Saura-Calixto F, Pérez-Jiménez J, Touriño S, Serrano J, Fuguet E, Torres JL, Goñi I (2010) Proanthocyanidin metabolites associated with dietary fibre from in vitro colonic fermentation and proanthocyanidin metabolites in human plasma. Mol Nutr Food Res 54:939–946. https://doi.org/10.1002/mnfr.200900276

    Article  CAS  PubMed  Google Scholar 

  53. Goñi I, Serrano J (2005) The intake of dietary fiber from grape seeds modifies the antioxidant status in rat cecum. J Sci Food Agric 85:1877–1881. https://doi.org/10.1002/jsfa.2213

    Article  CAS  Google Scholar 

  54. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227. https://doi.org/10.1038/nature11053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was funded by Plan Estatal de I + D + I through projects AGL2017-83653-R (AEI/FEDER, UE) and RTI2018-098288-B-I00 (MCIU/AEI/FEDER, UE) and by contracts with Biopolis SL (Valencia, Spain), CAUCE Foundation (Oviedo, Spain) and Alimerka Foundation (Llanera, Spain). NS. is granted by a postdoctoral contract awarded by the Fundación para la Investigación Biosanitaria de Asturias (FINBA).

Author information

Authors and Affiliations

  1. Department of Functional Biology, University of Oviedo, Oviedo, Spain

    Isabel Gutiérrez-Díaz & Sonia González

  2. Diet, Microbiota and Health Research Team, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

    Isabel Gutiérrez-Díaz, Nuria Salazar, Clara G. de los Reyes-Gavilán, Miguel Gueimonde & Sonia González

  3. Department of Microbiology and Biochemistry of Dairy Products), Spanish Research Council (IPLA-CSIC), Instituto de Productos Lácteos de Asturias, Villaviciosa, Spain

    Nuria Salazar, Clara G. de los Reyes-Gavilán & Miguel Gueimonde

  4. Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Madrid, Spain

    Jara Pérez-Jiménez

Authors
  1. Isabel Gutiérrez-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuria Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jara Pérez-Jiménez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clara G. de los Reyes-Gavilán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miguel Gueimonde
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sonia González
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.G., C.G.R. and S.G. designed the experimental work and wrote the manuscript. I.G.-D. carried out the nutritional and anthropometric determinations. N.S., M.G and C.G.R. were involved in gut microbiota analysis. J.P. provided information for dietary polyphenol assessment. All authors reviewed and approved the submitted version of the manuscript.

Corresponding author

Correspondence to Sonia González.

Ethics declarations

Conflicts of interest

The authors declare no conflicts of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gutiérrez-Díaz, I., Salazar, N., Pérez-Jiménez, J. et al. New players in the relationship between diet and microbiota: the role of macromolecular antioxidant polyphenols. Eur J Nutr 60, 1403–1413 (2021). https://doi.org/10.1007/s00394-020-02339-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-020-02339-5

Keywords

  • Dietary polyphenols
  • Macromolecular antioxidants
  • Microbiota
  • Non-extratable polyphenols