Ellagitannin-rich food consumption for dampening chronic inflammation: A spotlight on Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic condition characterized by phases of remission and intermittent periods of active disease with progressive damage to the gastrointestinal tract. Despite therapies, a degree of subclinical inflammation may persist in the gut mucosa, contributing to a risk of relapse. A diet rich in polyphenols, like ellagitannins (ETs), may be an important factor for long-term maintenance of quiescent IBD. ETs are present in various fruits (berries, pomegranate, nuts) and can be metabolised in the human colon to different urolithins according to microbiota composition (Tomás-Barberán 2017 Mol Nutr Food Res 61:1500901). Due to a lack of clinical trials, the translation of promising preclinical findings to humans seems to be limited. In our exploratory study, patients with IBD in remission with a high risk of relapse were asked to consume a pomegranate juice in order to test systemic and mucosal changes in inflammatory response markers relative to a placebo group (Scaioli 2019 Trials 20:327). Despite a relatively small subject number, after 12 weeks of pomegranate juice consumption, we found a significant downregulation of the levels of inflammation-related genes in PBMC. Contrarily, no effects were found on expression levels of inflammatory biomarkers in colon tissues, showing high variability. To go further in the understanding of the anti-inflammatory effect of ETs, we established in vitro models of mucosal and circulating macrophages. These cells are essential for intestinal homeostasis and can differentiate in either M1 (pro-inflammatory phenotype) or M2 (anti-inflammatory) in response to the cytokine milieu. We hypothesised that human urolithin metabotypes could affect the cell transcriptome and potentially be protective against inflammation. Metabotype 0 (urolithin non-producers) did not alter the transcriptome of M1 colonic macrophages, whereas urolithins lead to a repression of the NF-κB signalling pathway. The transcriptome of M1 circulating macrophages was minimally influenced by all ET metabolites, while in M2 circulating macrophages urolithins enhanced their anti-inflammatory properties. Together these data indicate that ET-rich food consumption can represent a supplement to conventional therapy for maintaining IBD remission, and people identified as urolithin producers may receive a much greater benefit. However, a confirmatory trial is necessary. Acknowledgement: study supported by the SIR Program (grant RBSI14LHMB).