Skip to main content
Top
Published in: BMC Geriatrics 1/2020

Open Access 01-12-2020 | Respiratory Microbiota | Study protocol

Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial

Authors: Simone Guglielmetti, Stefano Bernardi, Cristian Del Bo’, Antonio Cherubini, Marisa Porrini, Giorgio Gargari, Nicole Hidalgo-Liberona, Raul Gonzalez-Dominguez, Gregorio Peron, Raul Zamora-Ros, Mark S. Winterbone, Benjamin Kirkup, Paul A. Kroon, Cristina Andres-Lacueva, Patrizia Riso

Published in: BMC Geriatrics | Issue 1/2020

Login to get access

Abstract

Background

During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role.

Methods

MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome.

Discussion

Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols−microbiota−IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects.

Trial registration

The trial is registered at (ISRCTN10214981); April 28, 2017.
Literature
1.
2.
go back to reference Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, et al. Intestinal permeability - a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14(1):1–25.CrossRef Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, et al. Intestinal permeability - a new target for disease prevention and therapy. BMC Gastroenterol. 2014;14(1):1–25.CrossRef
3.
go back to reference Meier J, Sturm A. The intestinal epithelial barrier: does it become impaired with age? Dig Dis. 2009;27(3):240–5.PubMedCrossRef Meier J, Sturm A. The intestinal epithelial barrier: does it become impaired with age? Dig Dis. 2009;27(3):240–5.PubMedCrossRef
5.
go back to reference Camilleri M, Madsen K, Spiller R, Van Meerveld BG, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil. 2012;24(10):976.CrossRef Camilleri M, Madsen K, Spiller R, Van Meerveld BG, Verne GN. Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil. 2012;24(10):976.CrossRef
6.
go back to reference Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012;61(9):1355–64.PubMedCrossRef Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012;61(9):1355–64.PubMedCrossRef
7.
go back to reference Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science (80- ). 2012;338(6103):120–3.CrossRef Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan TJ, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science (80- ). 2012;338(6103):120–3.CrossRef
9.
go back to reference Malago J. Contribution of microbiota to the intestinal physicochemical barrier. Benef Microbes. 2015;6(3):295–3.PubMedCrossRef Malago J. Contribution of microbiota to the intestinal physicochemical barrier. Benef Microbes. 2015;6(3):295–3.PubMedCrossRef
10.
go back to reference Kiesslich R, Goetz M, Angus EM, Hu Q, Guan Y, Potten C, et al. Identification of epithelial gaps in human small and large intestine by confocal Endomicroscopy. Gastroenterology. 2007;133(6):1769–78.PubMedCrossRef Kiesslich R, Goetz M, Angus EM, Hu Q, Guan Y, Potten C, et al. Identification of epithelial gaps in human small and large intestine by confocal Endomicroscopy. Gastroenterology. 2007;133(6):1769–78.PubMedCrossRef
11.
go back to reference Queipo-Ortuno MI, Boto-Ordonez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R, et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. Am J Clin Nutr. 2012 Jun;95(6):1323–34.PubMedCrossRef Queipo-Ortuno MI, Boto-Ordonez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R, et al. Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. Am J Clin Nutr. 2012 Jun;95(6):1323–34.PubMedCrossRef
12.
go back to reference Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M. Six-week consumption of a wild blueberry powder drink increases Bifidobacteria in the human gut. J Agric Food Chem. 2011;59(24):12815–20.PubMedCrossRef Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M. Six-week consumption of a wild blueberry powder drink increases Bifidobacteria in the human gut. J Agric Food Chem. 2011;59(24):12815–20.PubMedCrossRef
13.
go back to reference Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JPE. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr. 2011;93(1):62–72.PubMedCrossRef Tzounis X, Rodriguez-Mateos A, Vulevic J, Gibson GR, Kwik-Uribe C, Spencer JPE. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr. 2011;93(1):62–72.PubMedCrossRef
14.
go back to reference Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85.PubMedPubMedCentralCrossRef Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19(5):576–85.PubMedPubMedCentralCrossRef
15.
go back to reference Ferrario C, Taverniti V, Milani C, Fiore W, Laureati M, De Noni I, et al. Modulation of fecal Clostridiales Bacteria and butyrate by probiotic intervention with lactobacillus paracasei DG varies among healthy adults. J Nutr. 2014;144(11):1787–96.PubMedCrossRef Ferrario C, Taverniti V, Milani C, Fiore W, Laureati M, De Noni I, et al. Modulation of fecal Clostridiales Bacteria and butyrate by probiotic intervention with lactobacillus paracasei DG varies among healthy adults. J Nutr. 2014;144(11):1787–96.PubMedCrossRef
16.
go back to reference Plöger S, Stumpff F, Penner G, Schulzke J, Gäbel G, Martens H, et al. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci. 2012;1258:52–9.PubMedCrossRef Plöger S, Stumpff F, Penner G, Schulzke J, Gäbel G, Martens H, et al. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci. 2012;1258:52–9.PubMedCrossRef
17.
go back to reference Wada M, Tamura A, Takahashi N, Tsukita S. Loss of claudins 2 and 15 from mice causes defects in paracellular Na + flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology. 2013;144(2):369–80.PubMedCrossRef Wada M, Tamura A, Takahashi N, Tsukita S. Loss of claudins 2 and 15 from mice causes defects in paracellular Na + flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology. 2013;144(2):369–80.PubMedCrossRef
18.
go back to reference Claesson MJ, Jeffery IB, Conde S, Power SE, O’connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–84.PubMedCrossRef Claesson MJ, Jeffery IB, Conde S, Power SE, O’connor EM, Cusack S, et al. Gut microbiota composition correlates with diet and health in the elderly. Nature. 2012;488(7410):178–84.PubMedCrossRef
19.
go back to reference Tiihonen K, Ouwehand AC, Rautonen N. Human intestinal microbiota and healthy ageing. Ageing Res Rev. 2010;9(2):107–16.PubMedCrossRef Tiihonen K, Ouwehand AC, Rautonen N. Human intestinal microbiota and healthy ageing. Ageing Res Rev. 2010;9(2):107–16.PubMedCrossRef
20.
go back to reference Biagi E, Candela M, Franceschi C, Brigidi P. The aging gut microbiota: new perspectives. Ageing Res Rev. 2011;10(4):428–9.PubMedCrossRef Biagi E, Candela M, Franceschi C, Brigidi P. The aging gut microbiota: new perspectives. Ageing Res Rev. 2011;10(4):428–9.PubMedCrossRef
22.
go back to reference Peron G, Hidalgo-Liberona N, González-Domínguez R, Garcia-Aloy M, Guglielmetti S, Bernardi S, et al. Exploring the Molecular Pathways behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications. J Agric Food Chem. 2019. https://doi.org/10.1021/acs.jafc.9b01687.PubMedCrossRef Peron G, Hidalgo-Liberona N, González-Domínguez R, Garcia-Aloy M, Guglielmetti S, Bernardi S, et al. Exploring the Molecular Pathways behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications. J Agric Food Chem. 2019. https://​doi.​org/​10.​1021/​acs.​jafc.​9b01687.PubMedCrossRef
23.
go back to reference Boto-Ordonez M, Urpi-Sarda M, Queipo-Ortuno MI, Tulipani S, Tinahones FJ, Andres-Lacueva C. High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: a randomized clinical trial. Food Funct. 2014 Aug;5(8):1932–8.PubMedCrossRef Boto-Ordonez M, Urpi-Sarda M, Queipo-Ortuno MI, Tulipani S, Tinahones FJ, Andres-Lacueva C. High levels of Bifidobacteria are associated with increased levels of anthocyanin microbial metabolites: a randomized clinical trial. Food Funct. 2014 Aug;5(8):1932–8.PubMedCrossRef
24.
go back to reference Cardonaa F, Andrés-Lacuevac C, Tulipania S, Tinahonesb FJ. María Isabel Queipo-Ortuño. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24:1415–22.CrossRef Cardonaa F, Andrés-Lacuevac C, Tulipania S, Tinahonesb FJ. María Isabel Queipo-Ortuño. Benefits of polyphenols on gut microbiota and implications in human health. J Nutr Biochem. 2013;24:1415–22.CrossRef
25.
go back to reference Zamora-ros R, Cherubini A, Urp M, Bandinelli S, Ferrucci L, Andres-lacueva C. High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults. J Nutr. 2013;143:1445–50.PubMedPubMedCentralCrossRef Zamora-ros R, Cherubini A, Urp M, Bandinelli S, Ferrucci L, Andres-lacueva C. High concentrations of a urinary biomarker of polyphenol intake are associated with decreased mortality in older adults. J Nutr. 2013;143:1445–50.PubMedPubMedCentralCrossRef
26.
go back to reference Agbor AG, Vinson JA, Donnelly PE. Folin-Ciocalteau reagent for Polyphenolic assay. Int J Food Sci Nutr Diet. 2014;3(8):147–56.CrossRef Agbor AG, Vinson JA, Donnelly PE. Folin-Ciocalteau reagent for Polyphenolic assay. Int J Food Sci Nutr Diet. 2014;3(8):147–56.CrossRef
27.
go back to reference Yates AA, Erdman JW, Shao A, Dolan LC, Griffiths JC. Bioactive nutrients - time for tolerable upper intake levels to address safety. Regul Toxicol Pharmacol. 2017;84:94–101.PubMedCrossRef Yates AA, Erdman JW, Shao A, Dolan LC, Griffiths JC. Bioactive nutrients - time for tolerable upper intake levels to address safety. Regul Toxicol Pharmacol. 2017;84:94–101.PubMedCrossRef
28.
go back to reference French Ministry of Health. Decree Establishing the List of Plants, Other than Fungi, Authorized in Food Supplements and the Conditions of Their Employment, F.R. Off J French Repub. 2014;. French Ministry of Health. Decree Establishing the List of Plants, Other than Fungi, Authorized in Food Supplements and the Conditions of Their Employment, F.R. Off J French Repub. 2014;.
30.
go back to reference Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). 2010;2010 Article ID bap024. Neveu V, Perez-Jiménez J, Vos F, Crespy V, du Chaffaut L, Mennen L, et al. Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). 2010;2010 Article ID bap024.
31.
go back to reference Seefeldt VD, Harrison GG. In: Anthropometric Standardization Reference Manual, Lohman TG, Roche AF, Martorell R, Eds. Champaign: Human Kinetics Books; 1988: pg 111. Seefeldt VD, Harrison GG. In: Anthropometric Standardization Reference Manual, Lohman TG, Roche AF, Martorell R, Eds. Champaign: Human Kinetics Books; 1988: pg 111.
32.
go back to reference Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42(6):1206–52.CrossRefPubMed Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42(6):1206–52.CrossRefPubMed
33.
go back to reference Knopfholz J, Disserol CCD, Pierin AJ, Schirr FL, Streisky L, Takito LL, et al. Validation of the friedewald formula in patients with metabolic syndrome. Cholesterol. 2014;2014:261878.PubMedPubMedCentralCrossRef Knopfholz J, Disserol CCD, Pierin AJ, Schirr FL, Streisky L, Takito LL, et al. Validation of the friedewald formula in patients with metabolic syndrome. Cholesterol. 2014;2014:261878.PubMedPubMedCentralCrossRef
35.
go back to reference Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP. How can we measure insulin sensitivity/resistance? Diabetes Metab. 2011;37(3):179–88.PubMedCrossRef Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP. How can we measure insulin sensitivity/resistance? Diabetes Metab. 2011;37(3):179–88.PubMedCrossRef
36.
go back to reference Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384.PubMedPubMedCentralCrossRef Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384.PubMedPubMedCentralCrossRef
37.
go back to reference Ciccia F, Guggino G, Rizzo A, Alessandro R, Luchetti MM, Milling S, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017;76(6):1123–32.PubMedCrossRef Ciccia F, Guggino G, Rizzo A, Alessandro R, Luchetti MM, Milling S, et al. Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis. Ann Rheum Dis. 2017;76(6):1123–32.PubMedCrossRef
38.
go back to reference Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernández-Real JM. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One. 2012;7(5):e37160.PubMedPubMedCentralCrossRef Moreno-Navarrete JM, Sabater M, Ortega F, Ricart W, Fernández-Real JM. Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS One. 2012;7(5):e37160.PubMedPubMedCentralCrossRef
39.
go back to reference Li C, Gao M, Zhang W, Chen C, Zhou F, Hu Z, et al. Zonulin regulates intestinal permeability and facilitates enteric Bacteria permeation in coronary artery disease. Sci Rep. 2016;6:29142.PubMedPubMedCentralCrossRef Li C, Gao M, Zhang W, Chen C, Zhou F, Hu Z, et al. Zonulin regulates intestinal permeability and facilitates enteric Bacteria permeation in coronary artery disease. Sci Rep. 2016;6:29142.PubMedPubMedCentralCrossRef
40.
go back to reference Amar J, Lange C, Payros G, Garret C, Chabo C, Lantieri O, et al. Blood Microbiota Dysbiosis Is Associated with the Onset of Cardiovascular Events in a Large General Population: The D.E.S.I.R. Study. PLoS One. 2013;8(1):e54461.PubMedPubMedCentralCrossRef Amar J, Lange C, Payros G, Garret C, Chabo C, Lantieri O, et al. Blood Microbiota Dysbiosis Is Associated with the Onset of Cardiovascular Events in a Large General Population: The D.E.S.I.R. Study. PLoS One. 2013;8(1):e54461.PubMedPubMedCentralCrossRef
41.
go back to reference Lelouvier B, Servant F, Païssé S, Brunet AC, Benyahya S, Serino M, et al. Changes in blood microbiota profiles associated with liver fibrosis in obese patients: a pilot analysis. Hepatology. 2016;64(6):2015–27.PubMedCrossRef Lelouvier B, Servant F, Païssé S, Brunet AC, Benyahya S, Serino M, et al. Changes in blood microbiota profiles associated with liver fibrosis in obese patients: a pilot analysis. Hepatology. 2016;64(6):2015–27.PubMedCrossRef
42.
go back to reference Lluch J, Servant F, Païssé S, Valle C, Valière S, Kuchly C, et al. The characterization of novel tissue microbiota using an optimized 16S metagenomic sequencing pipeline. PLoS One. 2015;10(11):e0142334.PubMedPubMedCentralCrossRef Lluch J, Servant F, Païssé S, Valle C, Valière S, Kuchly C, et al. The characterization of novel tissue microbiota using an optimized 16S metagenomic sequencing pipeline. PLoS One. 2015;10(11):e0142334.PubMedPubMedCentralCrossRef
43.
go back to reference Païssé S, Valle C, Servant F, Courtney M, Burcelin R, Amar J, et al. Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. Transfusion. 2016;56(5):1138–47.PubMedCrossRef Païssé S, Valle C, Servant F, Courtney M, Burcelin R, Amar J, et al. Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. Transfusion. 2016;56(5):1138–47.PubMedCrossRef
44.
go back to reference Nadkarni MA, Martin FE, Jacques NA, Hunter N. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology. 2002;148(Pt 1):257–66.PubMedCrossRef Nadkarni MA, Martin FE, Jacques NA, Hunter N. Determination of bacterial load by real-time PCR using a broad-range (universal) probe and primers set. Microbiology. 2002;148(Pt 1):257–66.PubMedCrossRef
45.
go back to reference Escudié F, Auer L, Bernard M, Mariadassou M, Cauquil L, Vidal K, et al. FROGS: find, rapidly, OTUs with galaxy solution. Bioinformatics. 2018;34(8):1287–94.PubMedCrossRef Escudié F, Auer L, Bernard M, Mariadassou M, Cauquil L, Vidal K, et al. FROGS: find, rapidly, OTUs with galaxy solution. Bioinformatics. 2018;34(8):1287–94.PubMedCrossRef
46.
go back to reference Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852–7.PubMedPubMedCentralCrossRef Bolyen E, Rideout JR, Dillon MR, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852–7.PubMedPubMedCentralCrossRef
47.
go back to reference Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: a versatile open source tool for metagenomics. PeerJ. 2016;18(4):e2584.CrossRef Rognes T, Flouri T, Nichols B, Quince C, Mahé F. VSEARCH: a versatile open source tool for metagenomics. PeerJ. 2016;18(4):e2584.CrossRef
48.
go back to reference Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27(16):2194–200.PubMedPubMedCentralCrossRef Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics. 2011;27(16):2194–200.PubMedPubMedCentralCrossRef
49.
go back to reference McMurdie PJ, Holmes S. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8(4):e61217.PubMedPubMedCentralCrossRef McMurdie PJ, Holmes S. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013;8(4):e61217.PubMedPubMedCentralCrossRef
50.
go back to reference Hasan NA, Young BA, Minard-Smith AT, et al. Microbial community profiling of human saliva using shotgun metagenomic sequencing. PLoS One. 2014;9(5):e97699.PubMedPubMedCentralCrossRef Hasan NA, Young BA, Minard-Smith AT, et al. Microbial community profiling of human saliva using shotgun metagenomic sequencing. PLoS One. 2014;9(5):e97699.PubMedPubMedCentralCrossRef
52.
go back to reference Valentini L, Ramminger S, Haas V, Postrach E, Werich M, Fischer A, et al. Small intestinal permeability in older adults. Physiol Rep. 2014;2(4):e00281.PubMedPubMedCentralCrossRef Valentini L, Ramminger S, Haas V, Postrach E, Werich M, Fischer A, et al. Small intestinal permeability in older adults. Physiol Rep. 2014;2(4):e00281.PubMedPubMedCentralCrossRef
Metadata
Title
Effect of a polyphenol-rich dietary pattern on intestinal permeability and gut and blood microbiomics in older subjects: study protocol of the MaPLE randomised controlled trial
Authors
Simone Guglielmetti
Stefano Bernardi
Cristian Del Bo’
Antonio Cherubini
Marisa Porrini
Giorgio Gargari
Nicole Hidalgo-Liberona
Raul Gonzalez-Dominguez
Gregorio Peron
Raul Zamora-Ros
Mark S. Winterbone
Benjamin Kirkup
Paul A. Kroon
Cristina Andres-Lacueva
Patrizia Riso
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2020
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-020-1472-9

Other articles of this Issue 1/2020

BMC Geriatrics 1/2020 Go to the issue