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      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

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          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.

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          Most cited references28

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          Benefits of polyphenols on gut microbiota and implications in human health.

          The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship "polyphenols ↔ microbiota" are still poorly understood. Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health. Copyright © 2013 Elsevier Inc. All rights reserved.
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            The Brain-Gut-Microbiome Axis

            Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.
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              Intestinal permeability – a new target for disease prevention and therapy

              Data are accumulating that emphasize the important role of the intestinal barrier and intestinal permeability for health and disease. However, these terms are poorly defined, their assessment is a matter of debate, and their clinical significance is not clearly established. In the present review, current knowledge on mucosal barrier and its role in disease prevention and therapy is summarized. First, the relevant terms ‘intestinal barrier’ and ‘intestinal permeability’ are defined. Secondly, the key element of the intestinal barrier affecting permeability are described. This barrier represents a huge mucosal surface, where billions of bacteria face the largest immune system of our body. On the one hand, an intact intestinal barrier protects the human organism against invasion of microorganisms and toxins, on the other hand, this barrier must be open to absorb essential fluids and nutrients. Such opposing goals are achieved by a complex anatomical and functional structure the intestinal barrier consists of, the functional status of which is described by ‘intestinal permeability’. Third, the regulation of intestinal permeability by diet and bacteria is depicted. In particular, potential barrier disruptors such as hypoperfusion of the gut, infections and toxins, but also selected over-dosed nutrients, drugs, and other lifestyle factors have to be considered. In the fourth part, the means to assess intestinal permeability are presented and critically discussed. The means vary enormously and probably assess different functional components of the barrier. The barrier assessments are further hindered by the natural variability of this functional entity depending on species and genes as well as on diet and other environmental factors. In the final part, we discuss selected diseases associated with increased intestinal permeability such as critically illness, inflammatory bowel diseases, celiac disease, food allergy, irritable bowel syndrome, and – more recently recognized – obesity and metabolic diseases. All these diseases are characterized by inflammation that might be triggered by the translocation of luminal components into the host. In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.

                Author and article information

                Contributors
                patrizia.riso@unimi.it
                Journal
                BMC Geriatr
                BMC Geriatr
                BMC Geriatrics
                BioMed Central (London )
                1471-2318
                26 February 2020
                26 February 2020
                2020
                : 20
                : 77
                Affiliations
                [1 ]ISNI 0000 0004 1757 2822, GRID grid.4708.b, Department of Food, Environmental and Nutritional Sciences (DeFENS), , Università degli Studi di Milano, ; 20133 Milan, Italy
                [2 ]Geriatria, Accettazione Geriatrica e Centro di Ricerca per l’Invecchiamento, IRCCS INRCA, 60127 Ancona, Italy
                [3 ]ISNI 0000 0004 1937 0247, GRID grid.5841.8, Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Food Technology Reference Net (XaRTA), Nutrition and Food Safety Research Institute (INSA), Faculty of Pharmacy and Food Sciences, , University of Barcelona, ; 08028 Barcelona, Spain
                [4 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), , Instituto de Salud Carlos III, ; 08028 Barcelona, Spain
                [5 ]ISNI 0000 0001 2097 8389, GRID grid.418701.b, Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, , Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), ; Barcelona, Spain
                [6 ]ISNI 0000 0000 9347 0159, GRID grid.40368.39, Quadram Institute Bioscience, Norwich Research Park, ; Norwich, NR4 7UQ UK
                Author information
                http://orcid.org/0000-0002-9204-7257
                Article
                1472
                10.1186/s12877-020-1472-9
                7045478
                32102662
                af90524b-29ab-4c90-b195-ccc59ee2054c
                © The Author(s). 2020

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 September 2019
                : 12 February 2020
                Funding
                Funded by: Mipaaft
                Award ID: D.M. 8245/7303/2016
                Award Recipient :
                Funded by: MINECO
                Award ID: PCIN-2015-238
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000268, Biotechnology and Biological Sciences Research Council;
                Award ID: BB/R012512/1
                Categories
                Study Protocol
                Custom metadata
                © The Author(s) 2020

                Geriatric medicine
                gut barrier function,leaky gut,flavonoids,phenolics,inflammation,aging,inflamm-aging
                Geriatric medicine
                gut barrier function, leaky gut, flavonoids, phenolics, inflammation, aging, inflamm-aging

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