Vaginal metabolites may be an early predictor of spontaneous preterm birth

Vaginal metabolites may be early predictors of spontaneous preterm birth (sPTB), according to a recent study.

Although sPTB is a major cause of maternal and neonatal morbidity, there are few options for early risk identification and prevention. While the vaginal microbiome is associated with SPTB, the relationship between these 2 factors remains unclear.

Metabolites have shown associations with the microbiome, inflammation, and preterm birth, causing local and systemic effects. Researchers conducted a study to further understand the role of metabolites in SPTB.

The second trimester vaginal metabolome was measured in 232 pregnant women. Of those, 80 pregnancies ended prematurely. There were 635 metabolites identified, of which 549 were observed in more than half of the study population, and 108 of which were observed in the entire population.

Associations were found between the metabolome and the microbiome, but community state types (CSTs) were not well distinguished. Although microbiomes were well isolated. This indicates a strong but incomplete relationship between the vaginal microbiome and metabolome.

Six metabolite clusters (MC) were found, with no significant separation between the vaginal microbiome and CSTs. Polyamine metabolism was the most enriched metabolite sub-pathway within each MC. Also, the researchers found different enrichments of CST in MCs.

There was a significant difference between the metabolomes of black and white women, but only mild differences when looking at associations with MCs. Several MCs were significantly associated with SPTB in black women but not in white women. This indicated prematurity in black women rather than microbiome composition.

Four metabolites were significantly associated with sPTB, of which 3 were from exogenous sources. These 3 were ethyl β-glucopyranoside, tartrate, and diethanolamine. The researchers found these metabolites in more than 95% of the study population.

Choline, an essential nutrient, was found to have lower levels in women with subsequent sPTB. Low levels of choline are associated with low betaine levels. Since diethanolamine has been associated with impaired choline metabolism, the researchers hypothesized that high diethanolamine levels in SPTB could lower choline and betaine levels.

There were 13 vagal metabolites previously associated with SPTB. These sugars or sugar alcohol metabolites are found to be high in early preterm birth. Interactions with both race and SPTB time were found, with additional SPTB-associated xenobiotics also found.

These results showed enriched metabolite signatures among black women with SPTB. Exogenous metabolites were also associated with SPTB, indicating important risk factors.


Kindschuh WF, Baldini F, Liu MC, Liao J, Meydan Y, Lee HH, et al. Preterm birth is associated with xenobiotics and predicted by vaginal metabolome. Nat Microbiol. 2023. doi:10.1038/s41564-022-01293-8

Leave a Comment