Vaginal microbial profiling in a preterm birth high-risk cohort using shallow shotgun metagenomics

Abstract

Preterm birth (PTB) is a significant health problem globally, with an estimate of 15 million cases annually. Approximately 10% of neonates born early will die prematurely, while a subset will develop severe life-long morbidities. Unfortunately, preterm birth's syndromic nature has evaded prevention strategies, and it continues to impose a high burden on healthcare systems and families. The role of vaginal bacteria in triggering biomolecular causes of PTB has been recognised for years. However, translating this knowledge to practical diagnostic and therapeutic strategies has remained elusive. New techniques in high-throughput sequencing have improved our understanding of the nature and role of the vaginal microbiome during pregnancy. Several multi-ethnic and multi-geographical studies into the vaginal microbiome have identified five distinct bacterial profiles termed community state types (CSTs), one of which is positively associated with dysbiosis and increased risk of PTB. In a small pilot study of first-trimester vaginal microbial DNA obtained from pregnant women at high-risk of PTB, we compared the CST profiles generated using standard 16S amplicon sequencing with shallow shotgun metagenomics (SSM). Both methods identified the presence of the five CSTs as has been reported previously, although the metagenomic data showed greater taxonomic resolution and more accurate CST assignation. These findings suggest that SSM is a cost-effective and potentially superior alternative to 16S sequencing for vaginal microbiome analysis.