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BackgroundOlder subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses.MethodsA randomised, controlled, crossover study was performed involving 51 participants (>= 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline.ResultsAmong the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF

Berries represent an important source of bioactive compounds, among which, (poly)phenols are the main constituents. (Poly)phenols have been shown to have important biological activities and in particular, to take a relevant role in mediating the modulation of gut microbiota and human health. Gut microbiota constitute significant players in the metabolism of ingested (poly)phenols and consequently in their biological effects. However, the evidence regarding the mutual contribution between (poly)phenol intake and gut microbiota activity in humans is still unclear. The aim of the current systematic review was to collect and assess results from randomized clinical trials addressing the role of berries in the modulation of the gut microbiota composition and how this can contribute to the metabolism of berry (poly)phenols. When information was available, the interaction of berry-gut microbiota on human health was evaluated. A total of 16 trials were included and analyzed. Overall, berries and their (poly)phenols could represent a driver for the modulation of intestinal microbes. The gut microbiota catabolize (poly)phenols by producing bioactive metabolites which can positively affect both the composition of commensal microbiota and also the host health.

Quale ruolo può avere un “ambassador” in un programma di Faculty Development? Con il termine ambassador si identificano quei dipendenti che assumono, all’interno di programmi formali o anche informalmente, il ruolo di “agente del cambiamento”. Si tratta, cioè, di lavoratori che sono proattivi nel creare interesse, sperimentare e condividere le innovazioni promosse da un’organizzazione. Solitamente, i lavoratori che svolgono il ruolo di Ambassador sono motivati a impegnarsi in comportamenti promossi dall’organizzazione di appartenenza che risultano coerenti con alcuni aspetti salienti delle loro identità. Pertanto, di base c’è una identificazione con l’organizzazione e con quei valori e significati che vuole diffondere in quanto percepiti come parte integrante della propria identità. Da queste premesse nasce l’idea della costituzione di una rete interna di Faculty Development Ambassador (FDA) di Unimi che supporti la trasformazione dell’Ateneo verso una didattica maggiormente innovativa e student-centered. Di base, un FDA è dunque un docente che si identifica con questa sfida ed è appassionato di didattica. Possiede inoltre peculiari competenze ed è al centro di reti relazionali formali o informali, attraverso le quali si fa portavoce delle sperimentazioni sulle metodologie e modalità di didattica innovativa emergenti. Tale figura, si impegna, dunque, nel supportare il programma di FD sia mettendo in atto sperimentazioni e uno stile di insegnamento, coerente con questo fine, sia trasmettendo informazioni sulla didattica innovativa ai propri colleghi, anche raccogliendo i bisogni formativi della comunità accademica. Si tratta di attività di informal faculty development, legate alle community of practice, le quali possono avere un ruolo cruciale nel FD. Nel nostro contributo descriveremo fasi, risorse e strategie che ci hanno permesso di costruire un gruppo di circa 20 FDA, illustrando gli obiettivi che questo gruppo si è proposto.

Alla Statale di Milano dal 2019 è attivo un progetto di Faculty Development (FD) per gli RTDB neoassunti, appartenenti alle aree Scienze della vita (LS), Scienze umane (SH) e Scienze (PE) [1,2]. A oggi, sono state svolte 3 edizioni, ciascuna su progettazione, metodologie didattiche, valutazione; nelle ultime 2 edizioni, sono state effettuate esercitazioni sulla stesura dei learning outcomes (LO) e sugli strumenti di valutazione (SV) del proprio insegnamento (nell’edizione 2: costruire un MCQ; nella 3: partendo dalle modalità e strumenti attualmente utilizzati, proporre delle valide alternative). I docenti del FD hanno dato feedback [3,4] individualizzati agli RTDB sulla performance in entrambe le esercitazioni [5]. Obiettivi Rilevare la partecipazione degli iscritti al FD alle esercitazioni proposte; indagare la tipologia di feedback dato ai partecipanti; rilevare eventuali differenze rispetto all’area di appartenenza dei rispondenti e all’edizione (2 e 3). Metodi Sono stati raccolti dati riguardanti la frequenza di intervento per modulo (LO e SV) e la tipologia di feedback assegnato e si sono confrontati per area disciplinare ed edizione. Oltre a una statistica descrittiva, è stata effettuata un’analisi di contenuto dei feedback, creando le categorie: intervento di livello Basso (B), Medio (M) o Importante (I) (se B, l’RTDB aveva effettuato correttamente l’esercitazione). Risultati Partecipazione: hanno risposto alle esercitazioni sui LO circa metà dei partecipanti delle edizioni 2 e 3 (40/88; 31/59). L’area più partecipe è stata per entrambe le edizioni quella delle LS e PE; l’SH è stata quella meno rispondente. Per l’esercitazione sugli SV, la partecipazione nell’edizione 2 è stata molto bassa (8/88) rispetto alla 3 (30/59). I più partecipi nella 2 sono stati gli RTDB di PE, quelli meno gli RTDB di SH; mentre nella 3 gli RTDB di SH hanno risposto di più e hanno risposto meno quelli di LS. Feedback: per i LO, la maggior parte degli RTDB ha avuto feedback

The evaluation of food intake in older subjects is crucial in order to be able to verify adherence to nutritional recommendations. In this context, estimation of the intake of specific dietary bioactives, such as polyphenols, although particularly challenging, is necessary to plan possible intervention strategies to increase their intake. The aims of the present study were to: (i) evaluate the nutritional composition of dietary menus provided in a residential care setting; (ii) estimate the actual intake of nutrients and polyphenols in a group of older subjects participating in the MaPLE study; and (iii) investigate the impact of an eight-week polyphenol-rich dietary pattern, compared to an eight-week control diet, on overall nutrient and polyphenol intake in older participants. The menus served to the participants provided ~770 mg per day of total polyphenols on average with small variations between seasons. The analysis of real consumption, measured using weighed food diaries, demonstrated a lower nutrient (~20%) and polyphenol intake (~15%) compared to that provided by the menus. The feasibility of dietary patterns that enable an increase in polyphenol intake with putative health benefits for age-related conditions is discussed, with a perspective to developing dietary guidelines for this target population.

There is an increasing interest in investigating dietary strategies able to modulate the gut microbial ecosystem which, in turn, may play a key role in human health. Dietary fibers (DFs) are widely recognized as molecules with prebiotic effects. The main objective of this systematic review was to: (i) analyze the results available on the impact of DF intervention on short chain fatty acids (SCFAs) production; (ii) evaluate the interplay between the type of DF intervention, the gut microbiota composition and its metabolic activities, and any other health associated outcome evaluated in the host. To this aim, initially, a comprehensive database of literature on human intervention studies assessing the effect of confirmed and candidate prebiotics on the microbial ecosystem was developed. Subsequently, studies performed on DFs and analyzing at least the impact on SCFA levels were extracted from the database. A total of 44 studies from 42 manuscripts were selected for the analysis. Among the different types of fiber, inulin was the DF investigated the most (n = 11). Regarding the results obtained on the ability of fiber to modulate total SCFAs, seven studies reported a significant increase, while no significant changes were reported in five studies, depending on the analytical methodology used. A total of 26 studies did not show significant differences in individual SCFAs, while the others reported significant differences for one or more SCFAs. The effect of DF interventions on the SCFA profile seemed to be strictly dependent on the dose and the type and structure of DFs. Overall, these results underline that, although affecting microbiota composition and derived metabolites, DFs do not produce univocal significant increase in SCFA levels in apparently healthy adults. In this regard, several factors (i.e., related to the study protocols and analytical methods) have been identified that could have affected the results obtained in the studies evaluated. Future studies are

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 = 0.0

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and agerelated diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies.

Increasing evidence links intestinal permeability (IP), a feature of the intestinal barrier, to several pathological or dysfunctional conditions. Several host and environmental factors, including dietary factors, can affect the maintenance of normal IP. In this regard, food bioactives, such as polyphenols, have been proposed as potential IP modulators, even if the mechanisms involved are not yet fully elucidated. The aim of the present paper is to provide a short overview of the main evidence from in vitro and in vivo studies supporting the role of polyphenols in modulating IP and briefly discuss future perspectives in this research area.

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.

Growing evidence support association between polyphenol intake and reduced risk for chronic diseases, even if there is a broad debate about the effective amount of polyphenols able to exert such protective effect. The present systematic review provides an overview of the last 10-year literature on the evaluation of polyphenol intake and its association with specific disease markers and/or endpoints. An estimation of the mean total polyphenol intake has been performed despite the large heterogeneity of data reviewed. In addition, the contribution of dietary sources was considered, suggesting tea, coffee, red wine, fruit and vegetables as the main products providing polyphenols. Total flavonoids and specific subclasses, but not total polyphenols, have been apparently associated with a low risk of diabetes, cardiovascular events and all-cause mortality. However, large variability in terms of methods for the evaluation and quantification of polyphenol intake, markers and endpoints considered, makes it still difficult to establish an evidence-based reference intake for the whole class and subclass of compounds. Nevertheless, the critical mass of data available seem to strongly suggest the protective effect of a polyphenol-rich dietary pattern even if further well targeted and methodologically sound research should be encouraged in order to define specific recommendations.

Many studies suggest that distributing energy and nutrient intake across 4–5 eating occasions/day (rather than across three standard meals) could favourably affect human health. The inclusion of 1–2 snacks in the daily pattern alleviates the potential digestive and metabolic overload caused by fewer heavier meals and might contribute to meet recommendations for food groups (e.g. fruits, dairy) and nutrients like fibre and vitamins. The snack composition should be evaluated taking into account the whole day’s diet. In early and late ages, and for specific population groups, snacking may need to follow particular characteristics in order to be optimal, both in terms of composition and timing. This document, which is the result of a collaboration of experts across several fields of research, intends to provide a review of the current scientific literature on meal frequency and health, highlighting the beneficial effects of correct snack consumption across the human lifespan.