Multi-kingdom cervical microbiome structure in health and dysbiosis: a cross-sectional study from Kazakhstan.

INTRODUCTION

The cervicovaginal microbiome is a key determinant of reproductive health. Its multi-kingdom structure and ecological interactions remain insufficiently characterized across diverse populations. This study aimed to define the composition and cross-kingdom dynamics of the cervical microbiome in women without HPV infection and with normal cytology in a Kazakhstani population.

METHODS

In this cross-sectional study, cervical samples from 92 reproductive-age women were analyzed using whole-genome metagenomic sequencing to characterize bacterial, viral, fungal, and archaeal communities, together with predicted functional pathways. Microbial communities were stratified into community state types based on dominant bacterial species.

RESULTS

Bacterial composition differed markedly across community states, with Lactobacillus-dominated profiles associated with low diversity and anaerobe-rich communities associated with higher diversity. In contrast, viral, fungal, and archaeal diversity remained relatively stable, although descriptive compositional shifts indicated variation in bacteriophages, methanogenic archaea, and opportunistic fungi in non-Lactobacillus communities. Functional analyses indicated CST-associated pathway differences, suggesting greater metabolic flexibility in dysbiotic states, and exploratory network analysis revealed CST-associated restructuring of bacterial and cross-kingdom co-variation patterns. Notably, more than half of participants exhibited non-Lactobacillus-dominated communities despite the absence of infection or cytological abnormalities, indicating population-specific microbiome configurations.

DISCUSSION: Study demonstrates that the cervical microbiome is accompanied by exploratory cross-kingdom compositional variation and ecological states traditionally considered dysbiotic may represent stable, population-specific configurations, highlighting the need for context-dependent definitions of microbial health.