Objectives: Older subjects are more prone to develop inflammation and intestinal permeability (IP). Diets rich in (poly)phenols could represent a potential strategy to reduce IP. The goal of the present study was to test the hypothesis that a (poly)phenol-rich diet can affect markers of IP and inflammation in older subjects. Methods: A randomized, controlled, crossover study was carried out in which 66 subjects (≥ 60 years old) with increased IP were randomly assigned to one of two intervention groups: a (poly)phenol rich diet (PR-diet) or a control diet (C-diet). Each intervention was 8-week long and separated by an 8-week washout period. The PR-diet provided approximately twice the amount of total (poly)phenols compared to the C-diet. Serum and fecal samples, collected at the beginning and the end of each period, were used for the quantification of zonula occludens-1 (ZO-1), occludin, fecal zonulin, adiponectin, calprotectin, cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial (VE)-cadherin levels using ELISA kits. Results: Fifty-one out of 66 enrolled subjects completed the intervention. The PR-diet reduced fecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) compared to the C-diet. A time effect was observed for VE-cadherin levels showing a reduction (p = 0.038) following PR-diet, but not C-diet. Conversely, a significant increase in ZO-1 was registered (p = 0.001) after both the interventions (PR-diet and C-diet). No significant effect was observed for the other variables. Conclusions: Overall, the study data suggest that (poly)phenols, in the context of a PR-diet, may reduce IP and inflammation in older subjects. The data also suggest that serum and fecal calprotectin may be promising targets in studies of the effects of (poly)phenols on systemic and intestinal inflammation in this target population. Funding Sources: The study was funded within the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL), granted by Mipaaf and partially supported under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3 by the Italian Ministry of University and Research through the European Union—NextGenerationEU funding.
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