Abstract
Toxin-antitoxin (TA) systems are widespread genetic modules in prokaryotes, implicated in diverse functions including stress adaptation, genome stability, and virulence. While extensively studied in pathogenic bacteria, their presence and roles in beneficial gut microbes like Bifidobacterium remain underexplored. This review consolidates current knowledge on type II TA systems within the Bifidobacterium genus, highlighting their diversity, genomic context, and potential functional roles. Genomic analyses reveal a predominance of MazEF and RelBE families, with other systems such as VapBC, YefM-YoeB, and PumAB also identified, albeit less frequently. Experimental validation is limited, with most studies focused on B. longum strains. Emerging evidence suggests that these systems may contribute to acid and osmotic stress responses and mobile genetic element maintenance. The species- and strain-specific distribution of TA loci suggests their potential utility as molecular markers for strain-level microbiome analysis. Given their multifaceted roles, further functional studies are warranted to elucidate the biological significance of TA systems in Bifidobacterium and their implications for gut health and probiotic efficacy.