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.

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 ( 65 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

A randomised controlled trial to assess the impact of a polyphenol-enriched diet on intestinal permeability in the elderly: The MaPLE study

Intestinal permeability increases in elderly populations and can result in increased systemic inflammation and contribute to low grade chronic inflammation. The barrier function of the gut can be affected by the gut microbiota and by dietary components. Dietary intervention strategies have the potential to improve intestinal barrier function either directly by affecting intestinal tissue functions or indirectly by beneficially altering the structure/function of the gut microbiota. In the context of a diet-microbiota-intestinal permeability (IP) axis, food bioactives such as polyphenols are a good candidate because there is emerging evidence that they can (i) affect the expression of intestinal tight junction proteins and (ii) beneficially alter gut microbiota profiles by increasing the populations of commensal bacteria. Within this framework the MaPLE project* (Microbiome mAnipulation through Polyphenols for managing gut Leakiness in the Elderly) has been developed to test the hypothesis that an increased intake of polyphenol-rich foods can reduce IP and lower inflammogenic bacterial factors in the bloodstream, promoting a protective metabolic phenotype in the elderly. The first specific tasks addressed have been the development of a polyphenol-rich dietary pattern to use for the intervention study and the evaluation of intestinal permeability in the target population. A polyphenol rich dietary pattern has been developed for the randomised, controlled cross-over dietary intervention study (polyphenol-rich (PR)-diet versus control (C)-diet) carried out on subjects (>60 y) living in a well-controlled setting (i.e. nursing home and associated independent houses at OIC Foundation, Padua Italy). To define the PR-diet, baseline polyphenol intake was firstly calculated through the analysis of recipes used to prepare the daily menu served at OIC Foundation (using www.phenol-explorer.eu). Mean baseline polyphenol intake in the target population was estimated to be about 750 mg/day. Three daily portions of polyphenol-rich food products were added to the PR-diet in order to double the amount regularly introduced by the older volunteers. PR-foods included: berries and derived products, blood oranges and derived products, pomegranate juice, Renetta apple and pur\ue9e, green tea and dark chocolate products. The control treatment (C-diet) was defined in order to be comparable in terms of energy intake and nutrient composition except for the polyphenol-rich products. IP evaluation in the volunteers was performed by quantifying serum zonulin levels using an ELISA kit).Where possible, IP was also evaluated using a multi-sugar test which involves quantifying sugars in 6 h urine collections following the intake of 5 g of lactulose and 1 g of mannitol. High IP is conveyed for urine lactulose (L)/mannitol (M) ratio > 0.03, evaluated through mass spectrometry analysis

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

17nonenoneDel Bo' C; Bernardi S; Cherubini A; Porrini M; Gargari G; Hidalgo-Liberona N; González-Domínguez R; Zamora-Ros R; Peron G; Marino M; Gigliotti L; Winterbone MS; Kirkup B; Kroon PA; Andres-Lacueva C; Guglielmetti S; Riso PDel Bo', C; Bernardi, S; Cherubini, A; Porrini, M; Gargari, G; Hidalgo-Liberona, N; González-Domínguez, R; Zamora-Ros, R; Peron, G; Marino, M; Gigliotti, L; Winterbone, Ms; Kirkup, B; Kroon, Pa; Andres-Lacueva, C; Guglielmetti, S; Riso,