Citrus Pomace-Derived Plant Complexes Enhance Caco-2 Wound Closure In Vitro and Modulate Selected Probiotic Strains

Citrus processing by-products represent a sustainable source of bioactive plant complexes with potential applications in intestinal health. This study investigated the effects of standardized food-grade orange (OE) and lemon (LE) pomace extracts and their simulated gastrointestinal digestates (DIGs) on intestinal epithelial responses and selected probiotic strains. Caco-2 cells were used to assess cytotoxicity, epithelial wound closure, and, in differentiated monolayers challenged with lipopolysaccharide (LPS), extracellular levels of SOD2, catalase, Nrf2, IL-6, IL-8, TNF-α, and IL-1β. In parallel, the effects of OE, LE, and their corresponding DIGs on the growth and cell-surface hydrophobicity of four probiotic lactic acid bacteria were evaluated. OE and LE DIGs were non-cytotoxic and promoted epithelial wound closure in a concentration- and time-dependent manner. In LPS-challenged monolayers, both DIGs counteracted alterations in extracellular oxidative stress-related proteins and reduced pro-inflammatory cytokine levels without affecting cell viability. OE and LE also produced strain-dependent effects on probiotic growth and cell-surface hydrophobicity, which were modified by gastrointestinal digestion. Overall, these findings extend previous evidence on the intestinal bioactivity of Citrus pomace-derived plant complexes and support their further investigation as sustainable food-grade ingredients for gut health applications.