New Insight and Knowledge on anti-inflammatory Effectiveness of dietary phenolics: a work-in-progress report of the NIKE Project

Diet may be an important factor in managing inflammatory bowel disease (IBD) symptoms. Patients with IBD who reached clinical remission have an expected relapse rate of ≈50%. We aim to explore the pomegranate juice supplementation as a potential strategy for the prevention of clinical relapse in asymptomatic IBD patients at high risk of flare. Methods: Faecal calprotectin is used as a surrogate marker of mucosal inflammation to predict the risk of relapse [1]. In a double-blind, randomised controlled trial (RCT), patients with IBD, ulcerative colitis and Crohn's disease, in stable clinical remission (≥3 months) have to consume either 125 mL pomegranate juice or placebo twice daily for 12 weeks. Before and after each intervention, biological samples (blood, urine, stool, and bowel biopsies) are collected. A food frequency questionnaire [2] and a dietary diary are administered. This trial is registered at ClinicalTrials.gov as NCT03000101 and conducted at the St. Orsola-Malpighi Hospital in Bologna (Italy). Results: Clinical, biochemical, and endoscopic parameters are assessed. The primary outcome is to measure changes to the faecal calprotectin. The secondary outcomes include systemic and mucosal changes of biochemical and molecular inflammatory response markers [3]. The compliance of trial participants is tested by a uHPLC system coupled to a mass spectrometer to quantify ellagitannin (ET)-derived metabolites in plasma and urine. Plasma level of trimethylamine-N-oxide is also evaluated as a potential biomarker of disease activity in IBD [4]. The recruitment is currently ongoing; no adverse events are observed. Furthermore, we are studying the effect of different combinations of ET-derived metabolites on modulation of expression of selected inflammatory response genes in polarised primary human macrophages [5]. Conclusions: The screening procedure is appeared to be feasible; the main reason why individuals are not included in the study is the treatment with corticosteroids within the last 2 months. Because the RCT is still ongoing, no final results can be presented. The in vitro preliminary findings suggest that supplementation with ET-derived metabolites may modulate the inflammation processes in polarised human macrophages. Further experiments and analysis are underway. Acknowledgments. This study is funded by the Italian Ministry of Education, University and Research MIUR - SIR Programme (grant no. RBSI14LHMB, funded to F. Danesi). Pomegranate juice is supplied by Gat Foods (M.P. Hefer; Israel). All experimental beverages are provided by Conserve Italia (Bologna; Italy). References. [1] Konikoff & Denson. Inflamm Bowel Dis 2006; 12:524-34. [2] Pellegrini et al. J Nutr 2007; 137:93-8. [3] Mesko et al. BMC Med Genomics 2010; 3:15. [4] Wilson et al. Dig Dis Sci 2015; 60:3620-30. [5] Dall’Asta et al. Nutr Metab Cardiovasc Dis 2012; 22:387-92.