Maternal factors associate with microbiota-derived extracellular vesicle profiles in pregnancy: a clinical cohort study.

BACKGROUND

While most clinical microbiome research has investigated gut microbiota, less is known about extracellular vesicles (EVs) produced by microbiota. Microbiota-derived EVs form a distinct taxonomic entity from the gut microbiota. Recently, microbiota-derived EVs from maternal microbiota have been shown to reach the fetus, which could be an important mechanism of microbiota-host interaction during the fetal period. We hypothesized that maternal factors could change the composition of microbiota-derived EVs during pregnancy.

METHODS

We compared the influence of antibiotics and maternal weight on microbiota-derived EVs secreted by maternal microbiota during pregnancy. We collected fecal samples from 60 pregnant women and 18 amniotic fluid samples from those undergoing C-section. Microbiota-derived EVs were isolated from the samples using size-exclusion chromatography and density-gradient ultracentrifugation and characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). RNA was isolated from the microbiota-derived EVs and converted to complementary DNA (cDNA), and 16 S rRNA gene sequencing was performed.

RESULTS

Altogether, 18 (30%) women had received antibiotics during pregnancy and 37 (62%) during delivery. Twenty (33%) women were lean, 27 (45%) had overweight and 13 had obesity (22%) during the first trimester. Taxonomic diversity of microbiota-secreted microbiota-derived EVs was lower in women exposed to antibiotics during pregnancy. When women exposed to antibiotics during delivery were excluded, the differences were not statistically significant. The microbiota-derived EVs differed in the amniotic fluid and maternal feces in women with overweight and obesity, gestational diabetes (GDM), and those who gained > 15 kg during pregnancy, as many bacterial origins of microbiota-derived EVs were depleted in these women. A beta diversity analysis of microbiota-derived EVs from fecal samples showed significant differences between the overweight and obesity groups. Diversity analysis showed no differences in various health factors during pregnancy, including asthma, allergies, or smoking.

CONCLUSIONS

Maternal factors influence the composition of microbiota-derived extracellular vesicles in feces and amniotic fluid of pregnant women, which may change host-microbiota interaction in the fetal period.