Genomic Insights into Probiotic Lactococcus lactis T-21, a Wild Plant-Associated Lactic Acid Bacterium, and Its Preliminary Clinical Safety for Human Application

<i>Lactococcus lactis</i> T-21 is a lactic acid bacterium isolated from wild cranberries in Japan that demonstrates significant immunomodulatory properties and has been incorporated into commercial health products. However, probiogenomic analyses specific to T-21 have remained largely unexplored. This study performed a thorough genomic characterisation of T-21 and evaluated its safety in initial clinical trials. Genomic analysis revealed substantial genetic diversity and metabolic capabilities, including enhanced fermentative potential demonstrated by its ability to metabolise a wide range of plant-derived carbohydrates, and genetic determinants associated with exopolysaccharide biosynthesis and nisin production, distinguishing T-21 from domesticated dairy strains. These attributes, reflective of its wild plant origin, may contribute to its metabolic versatility and unique probiotic functionalities. A preliminary clinical trial assessing the safety of T-21-fermented milk in healthy Japanese adults indicated no significant adverse outcomes, corroborating its safety for human consumption. Together, these findings support the feasibility of utilising non-dairy, wild plant-origin strains in dairy fermentation processes as probiotics. This study expands our understanding of the genomic basis for T-21's probiotic potential and lays the groundwork for further investigations into its functional mechanisms and potential applications in promoting human health.