(799) Microbes common in a Lactobacillus-deplete microbiota are negatively correlated with lipid metabolite abundance in pregnancy

A lipid-deplete cervicovaginal (CV) microenvironment is associated with short cervix, a sonographic marker of premature cervical remodeling and risk factor for spontaneous preterm birth (sPTB). Select CV microbiota have been implicated in cervical remodeling preceding sPTB. Whether lipid metabolites are associated with specific CV microbes remains unknown. We sought to examine correlations between cervicovaginal microbes and lipid metabolites in pregnancy.


Study Design:

This was a secondary analysis of a completed prospective pregnancy cohort. CV fluid was obtained between 20-24 weeks’ gestation. Participants selected for metabolomic profiling were frequency matched by birth outcome and CV microbiota profile. Microbiota was analyzed by 16S rRNA sequencing. Microbes present in at least half of the cohort were included for analyses. Metabolites (n=21) were chosen for analysis if significantly associated with short cervix in a prior analysis. Metabolite levels below the limit of detection (LOD) were imputed with the LOD/√2. Bacterial abundance and volume normalized lipid levels were log₂ transformed. Pearson correlation coefficients were calculated. Significance was determined using a Bonferroni P value threshold of P< 8.5E-5 (0.05/588 comparisons).


Results:

This analysis included 272 participants (Table 1). Lactobacillus crispatus was positively correlated with multiple lipid metabolites, while Megasphaera, Atopobium vaginae, Sneathia sanguinegens, and Gardnerella vaginalis were negatively correlated with multiple lipid metabolites (Fig. 1). Glycosyl-N-palmitoyl-sphingosine and behenoyl sphingomyelin correlated most commonly with microbial abundance.


Conclusion:

Anaerobes common in a Lactobacillus-deplete microbiota are negatively correlated with CV lipid metabolite abundance, particularly sphingolipids. This class of lipids promotes stabilization of cell membranes. Whether our findings reflect increased host cell turnover in response to anaerobes, increased microbial lipid utilization or degradation, or decreased lipid production warrants future investigation. SMFM/AAOGF (KG), 5R01NR014784 (ME)