Microbiome-producing SCFAs are associated with preterm birth via trophoblast function modulation.

Area of Science:

• Microbiology
• Obstetrics
• Metabolomics

Background:

• Preterm birth (PTB) is a major cause of infant mortality and morbidity, with complex and incompletely understood etiology.
• The cervicovaginal microbiome and its metabolites, like short-chain fatty acids (SCFAs), are implicated in PTB risk.
• Understanding these microbial-placental interactions is crucial for developing predictive and preventive strategies.

Purpose of the Study:

• To investigate the association between cervicovaginal microbiota composition, SCFA levels, and PTB.
• To explore the functional role of SCFAs in placental trophoblast cells.
• To identify potential biomarkers for the prediction and diagnosis of PTB.

Main Methods:

• 16S rRNA gene sequencing and targeted metabolomics on cervicovaginal swabs from pregnant women.
• In vitro functional assays using placental trophoblast cells (HTR8/SVneo).
• Integrated analysis of microbial and metabolic data, including gas chromatography-mass spectrometry.

Main Results:

• Significant cervicovaginal dysbiosis (reduced lactobacilli, increased anaerobes) was associated with PTB (P=0.036).
• Higher acetic acid levels were found in the preterm group (P=0.047), positively correlated with Gardnerella vaginalis.
• A diagnostic marker set (pregnancy type, acetic acid, community state type) accurately predicted PTB.
• Acetate promoted IL-8, IL-6, and trophoblast cell migration/invasion via ERK1/2 signaling.

Conclusions:

• Cervicovaginal microbiota dysbiosis is a significant etiological factor in PTB.
• Cervicovaginal microbiota and SCFAs can be used for PTB prediction and diagnosis.
• Findings support the microbiota-placenta axis theory and suggest potential for microecological interventions.