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Background Traditional research on the female reproductive tract (FRT) microbiome has focused on the dominance of bacteria, particularly Lactobacillus , as a marker of health. This bacteriocentric paradigm, however, cannot fully explain clinical enigmas like the high recurrence of bacterial vaginosis (BV) or the persistence of HPV infection. This review introduces a new pan-microbiome framework that highlights the overlooked roles of the virome and mycobiome as the ecosystem’s neglected components. Methods We conducted a systematic scoping review following the PRISMA-ScR guidelines. We searched PubMed, Embase, and Web of Science databases for studies published up to October 2025. Inclusion criteria focused on original research and metagenomic studies examining the female reproductive tract (FRT) virome, mycobiome, and bacteriome, specifically their interactions and clinical associations with bacterial vaginosis (BV) and HPV persistence. Data were extracted and synthesized to evaluate the pan-microbiome framework. Results The virome and mycobiome, despite their low biomass, are increasingly recognized as potential ecosystem modulators. Bacteriophages, for instance, are proposed to act as community “modulators,” either through lytic cycles that maintain bacterial diversity or lysogenic cycles that may contribute to stabilizing pathogenic biofilms in dysbiosis like BV by introducing virulence genes. Similarly, fungi like Candida can transition from harmless commensals to pathogens when the protective bacterial balance is disturbed. Conclusion FRT health is an emergent property of the complex interactions among bacteria, viruses, and fungi. A comprehensive understanding requires a pan-microbiome perspective. Future therapeutic strategies should move beyond a “one-bug, one-drug” approach toward “ecosystem restoration,” using targeted methods like phage therapy or vaginal microbiota transplantation to attempt to restore the balance of the entire microbial community.
Liu et al. (Fri,) studied this question.