Genomic islands associated with host adaptation and probiotic-related functions in Streptococcus thermophilus

Streptococcus thermophilus is a GRAS/QPS bacterium widely used in the dairy industry for the production of yogurt, fermented milk, and cheese. Its adaptation from a commensal ancestor to the dairy environment involved extensive genomic remodeling, while horizontal gene transfer has further contributed to its evolution. Among mobile genetic elements, genomic islands (GEIs) represent important drivers of adaptation and diversification. This study investigated the genomic basis underlying the putative probiotic potential of 109 S. thermophilus strains through the analysis of their mobilome, functional gene cargo, and biosafety-associated traits. Phylogenomic analysis identified two major clusters of genomes, STH1 and STH2. Genes associated with probiotic-related functions, including cell wall and membrane biosynthesis, amino acid and carbohydrate metabolism, and secondary metabolite production, were predominantly found within the accessory and unique fractions of the genome. The panvirulome and panresistome were small, while features such as capsule-associated genes may contribute to probiotic performance. Most GEIs, as well as integrative conjugative and mobilizable elements, occupied conserved genomic regions across strains. STH2 strains exhibited greater genomic plasticity, with 20 equivalent GEIs identified among members of this lineage. Metabolic islands were the most abundant GEI category and concentrated on the majority of probiotic-associated functions, followed by virulence islands. Although metabolic activity was generally limited to a few substrates under both aerobic and anaerobic conditions, the metabolic island identified in strain CIRM-BIA 336 may support enhanced galactose utilization under anaerobic conditions through the tagatose-6-phosphate pathway. Our findings suggest that GEIs are associated with strain-specific probiotic potential of S. thermophilus and may contribute to ecological adaptation and metabolic versatility. At the same time, these elements act as major hotspots of genomic plasticity, particularly within STH2 strains. The limited virulence and resistance gene repertoire further supports the biosafety of this species and reinforces its suitability for industrial and probiotic applications.