One-year restoration of vaginal health: synergistic dynamics of microbiome and metabolome following the elimination of high-grade cervical intraepithelial neoplasia
ABSTRACT
Therapeutic elimination of high-grade cervical intraepithelial neoplasia (CIN) is widely implemented for cervical cancer prevention. Despite the demonstrated dysbiosis of vaginal microenvironment in high-grade CIN, its post-therapy restorations remain to be poorly understood, especially in functional aspects. This study aimed to characterize temporal changes in both vaginal microbiota (VM) and metabolome (VMeta) following therapeutic elimination of high-grade CIN. We conducted a longitudinal study of 32 HPV-positive women with high-grade CIN who underwent therapeutic procedures. Vaginal swabs were collected at baseline (pre-therapy) and at 6- and 12-month follow-up visits for integrated VM and VMeta analysis. We observed a gradual restoration of
Lactobacillus crispatus
levels from baseline to 12 months (
P
< 0.05). Concurrently, we detected significant decreases in dysbiosis-associated bacteria, including
Prevotella bivia
,
Ureaplasma parvum
, and
Peptoniphilus
sp. 6 months post-therapy compared to the baseline. VMeta analysis revealed distinct metabolic shifts across the follow-up periods. The early post-therapy phase (baseline to 6 months) was characterized by enrichment of glycerophospholipids and depletion of nucleotide metabolites, while the later phase (6–12 months) showed increases in flavonoids, lysophospholipids, bioactive amides, and amino acid metabolism. Integration of correlation and dynamic Bayesian network analysis indicated potential regulatory relationships and time-lag effects involving HPV infection,
L. crispatus
,
Bifidobacterium
sp.,
Streptococcus anginosus
,
Megasphaera
sp.,
U. parvum,
and those metabolites. This study enhances our understanding of a sequential restoration process post-therapy in the vaginal microenvironment.
IMPORTANCE
Therapeutic elimination of high-grade CIN is routine, yet functional recovery of the vaginal ecosystem is poorly defined. In a 12-month longitudinal multi-omics study of 32 women, we show stepwise restoration: progressive
L. crispatus
dominance with sustained decreases in dysbiosis-associated taxa (
P. bivia, U. parvum, Peptoniphilus
). Metabolically, an early rise in glycerophospholipids and fall in nucleotide metabolites is followed by later enrichment of flavonoids, lysophospholipids, bioactive amides, and amino acid derivatives. Correlation and dynamic Bayesian network analyses reveal putative regulatory links, time-lag effects, and downstream impacts of HPV clearance. These findings deliver a functional roadmap of post-therapy recovery, nominate measurable microbial–metabolite milestones and candidate biomarkers for monitoring, and suggest targets for adjunct interventions to accelerate re-establishment of protective states. This work informs precision follow-up in cervical cancer prevention programs.
