Host-microbiome interactions in preterm labor induced by microbial or sterile intra-amniotic inflammation or progesterone action blockade
Preterm birth, the leading cause of perinatal morbidity, often follows premature labor, a syndrome whose prevention remains a challenge. To better understand the relationship between premature labor and host-microbiome interactions, we conducted a mechanistic investigation using three preterm birth models. Our findings demonstrated that intra-amniotic delivery of LPS triggered inflammatory responses in the amniotic cavity and cervico-vaginal microenvironment, causing vaginal microbiome changes and active labor. Intra-amniotic delivery of IL-1alpha caused a moderate inflammatory response in the amniotic cavity but increasing inflammation in the cervico-vaginal space, leading to vaginal microbiome disruption and active labor. Conversely, progesterone action blockade by RU-486 triggered local immune responses during active labor but did not alter the vaginal microbiome. Preterm labor facilitated the ascension of cervico-vaginal bacteria into the amniotic cavity, despite the stimulus. This study provides compelling mechanistic insights into the dynamic host-microbiome interactions in the cervico-vaginal microenvironment leading to premature labor and birth.