Evidence for a Modulatory Effect of a 12‐Week Pomegranate Juice Intervention on the Transcriptional Response in Inflammatory Bowel Disease Patients Reducing Fecal Calprotectin Levels: Findings From a Proof‐of‐Principle Study

Ilaria Minato, Pedro Mena, Luigi Ricciardiello, Eleonora Scaioli, Andrea Belluzzi, Enrica Rotondo, Eleonora Derlindati, Barbara Montanini, Costanza Michelini, Nicole Tosi, Vicente Agullò Garcià, Gianfranco Picone, Carlo Mengucci, Sara Dobani, Paloma Salamanca, Alice Rosi, Margherita Dall'Asta, Letizia Bresciani, Claudio Curti, Enzo Spisni, Alessandra Dei Cas, Alessandra Bordoni, Francisco A. Tomás‐Barberán, Lynnette R. Ferguson, Daniele Del Rio, Francesca Danesi

Source abstract

ABSTRACT This study aimed at investigating the effects of pomegranate juice (POMJ) consumption on inflammatory biomarkers and gene expression in patients with inflammatory bowel disease (IBD) in clinical remission. In this randomized, placebo‐controlled trial, 16 subjects with IBD in remission consumed POMJ or placebo for 12 weeks. POMJ consumption significantly reduced fecal calprotectin (FC) and plasma endotoxin levels. Transcriptomic analysis of peripheral blood mononuclear cells revealed upregulation of genes involved in mucosal immunity, including aryl hydrocarbon receptor ( AHR ), neutrophil cytosolic factor 4 ( NCF4 ), and nuclear factor, interleukin 3 regulated ( NFIL3 ). Urolithin metabotypes were predominantly of the B type, associated with intestinal dysbiosis. No significant changes were observed in serum inflammatory markers or colonic mucosal cytokine expression. POMJ consumption reduced markers of intestinal inflammation and modulated gene expression related to mucosal immunity and barrier function in patients with IBD. These findings suggest the potential of POMJ as a beneficial dietary intervention for maintaining remission in IBD, highlighting the promise of targeted nutritional strategies in managing chronic inflammatory conditions. Further research is needed to elucidate the long‐term clinical implications of these molecular changes. Trial Registration ClinicalTrials.gov identifier: NCT03000101 .