TY - JOUR
T1 - A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects
T2 - The MaPLE randomised controlled trial
AU - Del Bo', Cristian
AU - Bernardi, Stefano
AU - Cherubini, Antonio
AU - Porrini, Marisa
AU - Gargari, Giorgio
AU - Hidalgo-Liberona, Nicole
AU - González-Domínguez, Raúl
AU - Zamora-Ros, Raul
AU - Peron, Gregorio
AU - Marino, Mirko
AU - Gigliotti, Letizia
AU - Winterbone, Mark S.
AU - Kirkup, Benjamin
AU - Kroon, Paul A.
AU - Andres-Lacueva, Cristina
AU - Guglielmetti, Simone
AU - Riso, Patrizia
N1 - Funding Information:
This work was completed as part of the MAPLE project (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) supported within the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, http://www.healthydietforhealthylife.eu/ ) granted by Mipaaf (Italy, D.M. 8245/7303/2016), MINECO (Spain, PCIN-2015-238), and BBSRC (U.K., BB/R012512/1). Cristina Andres-Lacueva was also supported by grant 2017SGR1546 from the Generalitat de Catalunya's Agency AGAUR, funds from CIBERFES (co-funded by the FEDER Program from the European Union), and ICREA Academia Award 2018. Additional funding was provided by the Biotechnology and Biological Sciences Research Council (UK) through an Institute Strategic Programme Grant (‘Food Innovation and Health’; Grant No. BB/R012512/1 1 and its constituent projects BBS/E/F/000PR10343 (Theme 1, Food Innovation) and BBS/E/F/000PR10346 (Theme 3, Digestion and Fermentation in the Lower GI Tract) to the Quadram Institute Bioscience. Raúl González-Domínguez thanks the “Juan de la Cierva” program from MINECO (FJCI-2015-26590). Raul Zamora-Ros was supported by the “Miguel Servet” program (CP15/00100) from the Institute of Health Carlos III (Co-funded by the European Social Fund (ESF) - ESF investing in your future). Cristian Del Bo’ was supported by “ Piano di sostegno alla ricerca- Linea 2, Azione A, Università degli Studi di Milano, DeFENS -grant number PSR2019- CDELB and PSR2018-CDELB ”.
Publisher Copyright:
© 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/5
Y1 - 2021/5
N2 - Background & aim: Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP. The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects. Methods: A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated. Results: Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women. Interestingly, a significant increase in fibre-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention. The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features. Conclusions: These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fibre-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations. This study was registered at www.isrctn.org as: ISRCTN10214981.
AB - Background & aim: Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP. The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects. Methods: A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated. Results: Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women. Interestingly, a significant increase in fibre-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention. The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features. Conclusions: These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fibre-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations. This study was registered at www.isrctn.org as: ISRCTN10214981.
KW - Ageing
KW - Flavonoids
KW - Gut barrier function
KW - Inflammation
KW - Leaky gut
KW - Phenolics
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U2 - 10.1016/j.clnu.2020.12.014
DO - 10.1016/j.clnu.2020.12.014
M3 - Article
AN - SCOPUS:85098661954
VL - 40
SP - 3006
EP - 3018
JO - Clinical Nutrition
JF - Clinical Nutrition
SN - 0261-5614
IS - 5
ER -