A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial.


Journal

Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603

Informations de publication

Date de publication:
05 2021
Historique:
received: 06 03 2020
revised: 02 12 2020
accepted: 12 12 2020
pubmed: 4 1 2021
medline: 1 9 2021
entrez: 3 1 2021
Statut: ppublish

Résumé

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. 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. 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. 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. ISRCTN10214981.

Sections du résumé

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.

Identifiants

pubmed: 33388204
pii: S0261-5614(20)30689-0
doi: 10.1016/j.clnu.2020.12.014
pii:
doi:

Substances chimiques

Haptoglobins 0
Polyphenols 0
Protein Precursors 0
zonulin 0

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3006-3018

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R012512/1
Pays : United Kingdom

Informations de copyright

Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no conflicts of interest.

Auteurs

Cristian Del Bo' (C)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Stefano Bernardi (S)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Antonio Cherubini (A)

Geriatria, Accettazione Geriatrica e Centro di Ricerca per l'Invecchiamento, IRCCS INRCA, 60127 Ancona, Italy.

Marisa Porrini (M)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Giorgio Gargari (G)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Nicole Hidalgo-Liberona (N)

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Instituto de Salud Carlos III, 08028 Barcelona, Spain.

Raúl González-Domínguez (R)

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Instituto de Salud Carlos III, 08028 Barcelona, Spain.

Raul Zamora-Ros (R)

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Spain.

Gregorio Peron (G)

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Instituto de Salud Carlos III, 08028 Barcelona, Spain.

Mirko Marino (M)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Letizia Gigliotti (L)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Mark S Winterbone (MS)

Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, United Kingdom.

Benjamin Kirkup (B)

Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, United Kingdom.

Paul A Kroon (PA)

Quadram Institute Bioscience, Norwich Research Park, Norwich NR4 7UQ, United Kingdom.

Cristina Andres-Lacueva (C)

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Instituto de Salud Carlos III, 08028 Barcelona, Spain.

Simone Guglielmetti (S)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy.

Patrizia Riso (P)

Università, degli Studi di Milano, Department of Food, Environmental and Nutritional Sciences (DeFENS), 20133 Milan, Italy. Electronic address: patrizia.riso@unimi.it.

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Classifications MeSH