The Vaginal Microbiome-Mitochondria Axis: Implications for Genital Tract Infections.

The vaginal microbiome influences epithelial and immune homeostasis through microbial metabolites, virulence factors, and other molecular signals, yet intracellular mechanisms translating microbial activity into host responses remain largely unexplored. Here, we propose the vaginal microbiome-mitochondria axis as a functional framework linking microbial activity to host-cell metabolism, redox signaling, immunity, and cell fate. We integrated evidence from vaginal microbiology, mitochondrial biology, mucosal immunology, and immunometabolism, distinguishing direct observations in the female genital tract from mechanistic evidence obtained in other host-microbe systems. Available evidence indicates that microbial products relevant to vaginal homeostasis and dysbiosis can modulate mitochondrial bioenergetics, reactive oxygen species generation and redox signaling, membrane potential, dynamics, and quality control pathways, while mitochondrial responses can influence epithelial integrity and antimicrobial and inflammatory functions. We further propose that the balance between mitochondrial adaptation and dysfunction may contribute to resolution or persistence of vaginal disorders and that incomplete mitochondrial recovery could contribute to an incomplete microbial ecosystem-host reset and recurrence. Although direct vaginal evidence remains limited, this framework identifies mitochondria as a potentially important functional interface between microbial ecology and host response and generates testable hypotheses for investigating whether mitochondrial homeostasis contributes to durable resolution of vaginal dysbiosis and infection.