Vaginal microbiome and metabolome associated with HPV persistence in Chinese women: a prospective study

Vaginal microbiome (VM) associated with the risk of persistent HPV infection and progression of cervical intraepithelial neoplasia (CIN). However, there is a deficiency in prospective studies investigating those associations, especially in functional aspects. This study included 76 HPV-positive Chinese women with the clinical outcomes of HPV infection. Participants were stratified into three groups: natural HPV clearance (HPV_C, n = 18), HPV persistence with CIN1 (HPV_PL, n = 20), or CIN2+ (HPV_PH, n = 38). Vaginal swabs were collected for integrated VM and vaginal metabolome as well as Bayesian network analysis. Lactobacillus -dominant (LD) communities, primarily composed of L. crispatus (CST_I) and L. iners (CST_III), correlated with HPV clearance and lower CIN grade. CST was the most significant factor influencing metabolomic profiles ( p < 0.0001). LD samples showed enrichment in amino acid metabolism, while non- Lactobacillus -dominant (NLD) samples exhibited elevated levels of metabolites involved in pyrimidine metabolism and biogenic amines. CST_I were enriched in amino acids metabolism and some other metabolites like indole-3-lactic acid compared to CST_III. Metabolomic variations by comparing LD and NLD samples were more significant than those across clinical groupings. Bayesian network analysis suggested a bidirectional relationship, with microbiome affecting HPV outcomes (CSTs → metabolites → Group) and HPV persistence potentially modulating microbiome (HPV persistence → CSTs → metabolites). Metabolic differences exist between LD and NLD environments, as well as between different Lactobacillus species. Interplays between VM, metabolome, and HPV infection outcomes appear bidirectional, with VM influencing HPV persistence through metabolic mediators, and HPV infection potentially modulating VM, thus establishing a feedback loop that further promotes HPV persistence and CIN progression.