Microbiome profiling of Grana Padano and Parmigiano Reggiano cheeses reveals cheese-specific biomarkers, psychobiotic potential, and bioprotective activities

: Grana Padano (GP), Trentingrana (TG), and Parmigiano Reggiano (PR) are among the finest Italian Protected Designation of Origin (PDO) cheeses. GP, TG, and PR undergo extensive proteolysis during ripening, where the microbiome metabolizes amino acids, producing flavour and bioactive molecules. We explored the microbiome, volatilome, and metaproteome of PDO GP (n = 42), TG (n = 18), and PR (n = 60). Findings revealed diverse microbial communities enriched in proteolytic microbes, associated with cheese-specific processing technology. Correlations between lactic acid bacteria strains and specific volatile compounds were identified in PR. Importantly, we identified genes involved in the production of neuroactive molecules, suggesting potential connections between cheeses consumption and mental health, along with genes related to bacteriocin biosynthesis, possibly enhancing cheese safety, shelf life, and process sustainability. This study provides novel insights into the functional attributes of long-ripened cheeses microbiome, highlighting their potential as sources of psychobiotics and bioprotective strains.