Chitosan nanoparticles loaded with olive pomace phenolics modulate gut microbiota and its metabolic response in vitro

Olive pomace (OP), the solid residue left from olive oil production, is rich in bio-functional compounds, particularly phenolics with well-documented health-promoting properties. However, OP remains largely underutilised, leading to the waste of a valuable food-processing by-product. Its exploitation is further hindered by the inherent chemical instability of phenolic compounds. To address these limitations, we developed a novel nano-encapsulated hydroalcoholic OP extract embedded within a chitosan matrix cross-linked with tripolyphosphate (OPFE-lyo-NPs), a formulation designed to protect bioactive compounds and enhance their targeted delivery to the gut. Using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), we investigated the impact of OPFE-lyo-NPs and a placebo (lyo-NPs) on gut bacterial communities and their metabolic activity before (T0), after 3 and 10 days of treatment (T3, T10), and 7 days washout (W7). Both formulations increased total short-chain fatty acid (SCFA) production, with OPFE-lyo-NPs inducing higher butyrate levels than lyo-NPs in both proximal (21.68 vs 13.32 mM) and distal colon (24.50 vs 18.81 mM) at T10. Phenolics-loaded nanoparticles promoted a potentially beneficial modulation of the gut microbiota, defined by an increased relative abundance of health-associated taxa such as Lactobacillus and Faecalibacterium , and a shift toward a more butyrogenic profile. While lyo-NPs also enriched several health-associated taxa, OPFE-lyo-NPs uniquely promoted polyphenol-responsive genera with known health benefits and suppressed potentially detrimental genera, including Blautia and Microbacterium . These results suggest that the chitosan-based nanoparticles effectively deliver OP phenolics to the colon, where they exert targeted modulatory effects on the gut ecosystem, supporting potential benefits for host health.