¿CHIOS MASTIC GUM FROM PISTACIA LENTISCUS AS A MODULATOR OF INFLAMMATION AND INTESTINAL BARRIER FUNCTION: AN IN VITRO AND CLINICAL INVESTIGATION.¿

Inflammatory Bowel Disease (IBD) is an immune-mediated disorder characterized by dysregulated inflammation and impaired intestinal barrier function. Although effective, current therapies present limitations, highlighting the need for complementary approaches. Chios Mastic Gum (CMG), a resin from Pistacia lentiscus, has shown anti-inflammatory and barrier-protective properties in preclinical models. During this PhD project, an integrated clinical and mechanistic study was conducted to evaluate CMG (trade name Selpic) in patients with IBD. A randomized, double-blind, placebo-controlled trial involved 31 adults diagnosed with ulcerative colitis or Crohn's disease who were in clinical remission yet exhibited subclinical inflammation. Standardized questionnaires and faecal biomarkers (calprotectin, zonulin), were utilized to assess clinical outcomes. Concurrently, in vitro experiments compared Selpic with its isolated Supermastic® triterpene fraction in Caco-2 cells and lipopolysaccharide-stimulated THP-1 macrophages. Clinically, no significant differences were observed in the questionnaires and calprotectin levels, although a downward trend was noted for the latter (p=0.062). Faecal zonulin levels showed a significant decrease over time (p=0.017), with within-group analysis indicating a significant reduction in the Selpic group (p=0.036). No intergroup treatment effect was identified (p=0.107). In vitro, Selpic was found to suppress pro-inflammatory cytokine levels, diminish reactive oxygen species, encourage anti-inflammatory macrophage polarization, and enhance the expression of ZO-1 tight junction protein. Still, it modulated the endocannabinoid system by reducing N-acylethanolamines SEA and PEA. Analysis of gut microbiota indicated no alterations in α-diversity, but a temporal shift in β-diversity was observed within the Selpic group. In conclusion, faecal zonulin levels decreased over time, with a significant reduction in the Selpic group, though no intergroup treatment effect was confirmed. These results, combined with in vitro immunomodulatory and barrier-restorative effects, support Selpic potential as an adjuvant nutraceutical in IBD management. Larger multicentre trials are warranted to validate its clinical utility.