Cervicovaginal microbiome composition and absolute quantity are associated with pelvic inflammatory disease

Pelvic inflammatory disease (PID), which involves infection and inflammation of the female reproductive tract, can lead to sequelae including chronic pelvic pain, ectopic pregnancy and tubal factor infertility. A causative pathogen is not identified in many PID cases (idiopathic PID) and does not develop in all women with a sexually transmitted infection or bacterial vaginosis. Therefore, there is a need to better understand the pathogenesis of PID. A case-control study was conducted to explore microbiome, antibiotic resistance and immune gene expression in PID. Microbial profiling using both 16S rRNA gene amplicon and metagenomic approaches revealed that bacterial vaginosis-associated bacteria such as <i>Gardnerella vaginalis</i>, <i>Fannyhessea vaginae</i>, <i>Ureaplasma parvum</i> and members of the <i>Prevotella</i> spp. were significantly enriched in PID cases, while healthy controls were associated with <i>Lactobacillus</i> (<i>L</i>.) <i>crispatus</i>. Quantitative analysis with species-specific quantitative real-time PCR (qPCR) indicated that a high copy number of <i>L. crispatus</i> (measured using calibrated copy estimates by qPCR) was strongly associated with cervical samples from women in the control group, whereas PID cases with this organism had low copies when measured using qPCR. Antibiotic resistance to tetracyclines was more frequently predicted in metagenome-assembled genomes from PID cases, and corresponding isolates cultured from cases were less susceptible to doxycycline (<i>L. iners</i>). Overall, this study supports that PID is associated with cervicovaginal dysbiosis and an absence or low quantity of <i>L. crispatus</i>.