In vitro bioavailability and gender-specific fermentation of an Opuntia ficus-indica extract combining cladodes and fruit skins with synergistic prebiotic and metabolic actions

Opuntia ficus-indica (OFI) is traditionally recognized for its antioxidant and health-promoting properties, yet evidence on the bioaccessibility, bioavailability, microbiota-related effects and mechanism of action of standardized OFI extracts remains scarce. Here, we investigated an OFI cladodes and fruit peels extract (cpOFI extract; aka RECOVERA®), a formulation characterized by consistently high levels of phenolic compounds. The extract was subjected to simulated digestion and colonic fermentation using microbiota from male and female donors, and its bioavailable fractions were tested in human primary skeletal muscle cells. Analysis revealed high concentrations of piscidic and eucomic acids, which remained stable under gastric conditions and showed high bioavailability. Colonic fermentation promoted the production of short-chain fatty acids, confirming prebiotic activity while preserving natural gender-related differences, with higher propionate in males and increased butyrate in females. In muscle cells, bioavailable fractions enhanced glucose uptake and glycogen accumulation. Overall, cpOFI extract emerges as a promising nutraceutical with dual benefits for metabolic regulation and gut health. • Standardized cpOFI extract is enriched with bioactive phenolic acids. • Piscidic and eucomic acids show gastric and intestinal bioaccessibility. • cpOFI fermentation promotes SCFA production and preserve gender differences. • cpOFI bioavailable fraction enhances glucose uptake and glycogen in muscle cells.