Epigenetics and the vaginal microbiome: influence of the microbiota on the histone deacetylase level in vaginal epithelial cells from pregnant women

BACKGROUND: Histone deacetylase (HDAC) influences the acetylation status of histones at gene promotor loci, providing an epigenetic mechanism that regulates gene expression. METHODS: We determined if variations in the composition of the vaginal microbiome in pregnant women were associated with alterations in the level of HDAC1 in vaginal epithelial cells and whether this influenced the concentration of compounds present in vaginal fluid. Vaginal epithelial cells were obtained from 150 women in their first trimester of pregnancy, lysed and assayed for HDAC1 by ELISA. Composition of the vaginal microbiome was determined by classification of sequences amplified from the V1-V3 region of bacterial ribosomal 16S rRNA genes. Vaginal secretions were assayed for total protein, matrix metalloproteinase (MMP)-8, the 70kDa heat shock protein (hsp70) and the D- and L-lactic acid isomers. RESULTS: Lactobacilli were numerically dominant in 119 (79.3%) of the women, with Lactobacillus crispatus being the most prevalent (45.3% of women). Gardnerella was the most prevalent non-Lactobacillus species (10.7% of women). The median HDAC1 level in epithelial cells was 6.1 ng/mL when lactobacilli predominated vs. 20.5 ng/mL when non-lactobacilli were dominant (P=0.0039). Levels were lowest when L.crispatus was dominant (3.8 ng/mL) and highest with Streptococcus dominance (38.1 ng/mi.). The concentration of HDAC1 was negatively correlated with the D-lactic acid level (P=0.0183) and positively correlated with concentrations of MMP-8 and hsp70 (P<0.0001) in the vaginal fluid. CONCLUSIONS: We propose that the composition of the vaginal microbiome and level of D-lactic acid, by influencing the HDAC1 level in vaginal epithelial cells, may epigenetically contribute to variations in the concentration of compounds in vaginal fluid.