Host-microbiome interactions in distinct subsets of preterm labor and birth

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. We report that intra-amniotic delivery of LPS triggers inflammatory responses in the amniotic cavity and cervico-vaginal microenvironment, causing vaginal microbiome changes and signs of active labor. Intra-amniotic IL-1α delivery causes a moderate inflammatory response in the amniotic cavity but increasing inflammation in the cervico-vaginal space, leading to vaginal microbiome disruption and signs of active labor. Conversely, progesterone action blockade by RU-486 triggers local immune responses accompanying signs of active labor without altering the vaginal microbiome. Preterm labor facilitates ascension of cervico-vaginal bacteria into the amniotic cavity, regardless of stimulus. This study provides compelling mechanistic insights into the dynamic host-microbiome interactions within the cervico-vaginal microenvironment that accompany premature labor and birth.