Linking integrative omics-based data fusion to in vitro gastrointestinal digestion reveals ripening-driven chemical signatures in Coppa Piacentina PDO

Dry-cured meat ripening drives complex biochemical transformations that shape both product identity and gastrointestinal behaviour. In this study, an integrative strategy was applied to investigate how ripening-driven chemical organisation of Coppa Piacentina Protected Designation of Origin (PDO) influences its gastrointestinal metabolic outcome. Previously generated metabolomic, lipidomic and volatilomic datasets obtained from undigested samples at different ripening stages (fresh, 60, 90, 180 and 240 days) were integrated using a data fusion framework to obtain a system-level description of ripening-associated chemical signatures. Samples from the same ripening stages (n = 3) were subjected to the standardized INFOGEST in vitro digestion protocol, and intestinal digested samples were characterized by untargeted metabolomics using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) together with free amino acid profiling. The untargeted analysis allowed the putative annotation of 1298 mass features mainly belonging to amino acids, peptides and lipid-related metabolites. Data fusion revealed coordinated molecular networks associated with ripening, highlighting proteolysis, lipid remodelling and oxidative processes. These ripening-driven signatures were not erased during digestion but translated into distinct intestinal metabolomic profiles. Short ripening induced moderate changes in bioaccessible metabolites, whereas prolonged ripening amplified digestive complexity, promoting the release of peptide derivatives and lipid-related metabolites without increasing total free amino acid release. Notably, selected γ-glutamyl peptides showed relative resistance to gastrointestinal degradation. These findings indicate that ripening acts as a system-level biochemical driver shaping both product composition and the metabolite profile generated during digestion.