Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis

Bacterial vaginosis (BV), the most common vaginal condition of reproductive-aged women, is associated with a highly diverse and heterogeneous microbiota. Here we present a proof-of-principle analysis to uncover the function of the microbiota using meta-RNA-seq to uncover genes and pathways that potentially differentiate healthy vaginal microbial communities from those in the dysbiotic state of bacterial vaginosis (BV). The predominant organism, Lactobacillus iners, was present in both conditions and showed a differing expression profile in BV compared to healthy. Despite its minimal genome, L. iners differentially expressed over 10% of its gene complement. Notably, in a BV environment L. iners increased expression of a cholesterol-dependent cytolysin, and of mucin and glycerol transport and related metabolic enzymes. Genes belonging to a CRISPR system were greatly upregulated suggesting that bacteriophage influence the community. Reflective of L. iners, the bacterial community as a whole demonstrated a preference for glycogen and glycerol as carbon sources under BV conditions. The predicted end-products of metabolism under BV conditions include an abundance of succinate and other short-chain fatty-acids, while healthy conditions are predicted to largely contain lactic acid. Our study underscores the importance of understanding the functional activity of the bacterial community in addition to characterizing the population structure when investigating the human microbiome.