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bioRxiv · 10.64898/2026.03.23.713732

Cervicovaginal Dysbiosis in HPV-Negative Women: Metagenomic Evidence Implicates Achromobacter in Female Infertility

Ali, H.·Sujan, M. S. I.·Nahar, K.·Ahmed, M. F.·Azmuda, N.·Akter, S.·Adnan, N.
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Abstract

The cervicovaginal microbiome is pivotal to reproductive health, yet its dynamics in HPV-negative women with gynaecological disorders remain underexplored. We investigated microbial diversity and taxonomic shifts in HPV-negative women from Bangladesh using 16S rRNA gene sequencing and shotgun metagenomics. Of 224 women screened, 136 were HPV-negative; 29 underwent 16S profiling, and three infertility-associated cases were further analyzed by shotgun metagenomics. Healthy controls exhibited low alpha diversity and a Lactobacillus-dominated profile (98.2%), reflecting ecological stability. In contrast, pathological cases displayed significantly elevated richness and evenness, reduced Lactobacillus (28.0%), and enrichment of anaerobic and opportunistic taxa, including Bifidobacterium (23.4%), Achromobacter (12.9%) and Sneathia (7.5%). Distinct microbial signatures emerged across clinical subgroups: pelvic inflammatory disease was enriched in Bifidobacterium, intra-menstrual bleeding retained moderate Lactobacillus, while infertility exhibited prominent dominance of Achromobacter (45.5%). Shotgun metagenomics confirmed Achromobacter spp. (A. ruhlandii, A. dolens, A. xylosoxidans) as the predominant taxa (84.9%) in infertility cases, accompanied by depletion of protective Lactobacillus. Functional inference revealed conserved metabolic backbones but disease-specific enrichment of stress-response and biosynthetic pathways, particularly in infertility and PID. Co-occurrence network analysis identified condition-specific microbial consortia, with Achromobacter forming infertility-associated clusters. This study represents the first integrated application of amplicon and shotgun metagenomic approaches to profile the cervicovaginal microbiota in HPV-negative women. It identifies Achromobacter as a potential microbial biomarker of infertility and highlights the urgent need for microbiome-informed diagnostics and targeted interventions to restore cervicovaginal homeostasis.

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Ali, H., Sujan, M. S. I., Nahar, K., Ahmed, M. F., Azmuda, N., Akter, S., Adnan, N.. 2026-03-25. Cervicovaginal Dysbiosis in HPV-Negative Women: Metagenomic Evidence Implicates Achromobacter in Female Infertility. https://doi.org/10.64898/2026.03.23.713732

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