Pistachio leaf waste transformed into a gut-targeted bioactive phytocomplex

The human gut microbiota is integral to host physiology, influencing immune responses, metabolic regulation, and digestion. Disruptions in this microbial community are linked to inflammatory and metabolic disorders. In this study, we explored the potential of pistachio leaf extract (PLE), a polyphenol-rich natural product, to support gut health. The extract, obtained from <i>Pistacia vera</i> leaves harvested in Sicily, was chemically characterized and assessed for prebiotic-like, antimicrobial, antioxidant, and anti-inflammatory effects. It promoted the growth of beneficial gut bacteria, inhibited pathogenic strains, and exhibited marked antioxidant activity. In patient-derived intestinal organoids, the extract reduced inflammation and enhanced antioxidant defenses, with no detectable cytotoxicity in human colon cells. These results suggested that PLE is a safe and multifunctional compound that may contribute to intestinal homeostasis, offering promise for its inclusion in future functional food formulations aimed at promoting gastrointestinal health.