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Updated: Jul 9, 2025
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Published on: January 27, 2019
Host-microbiome interactions in distinct subsets of preterm labor and birth
Jose Galaz1,2,3, Roberto Romero1,4,5, Jonathan M Greenberg1,2
1Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD 20892, USA.
Insights
Premature labor involves complex host-microbiome interactions. Different triggers affect the vaginal microbiome and amniotic cavity differently, influencing preterm birth risk.
Area of Science:
- Reproductive biology
- Microbiome research
- Immunology
Background:
- Preterm birth is a major cause of infant mortality and morbidity.
- Premature labor, a common precursor to preterm birth, is not well understood, particularly its relationship with the host microbiome.
- Understanding the mechanisms of premature labor is crucial for developing effective prevention strategies.
Purpose of the Study:
- To investigate the mechanistic relationship between premature labor and host-microbiome interactions.
- To elucidate how different stimuli initiate labor and impact the cervico-vaginal and amniotic environments.
- To determine the role of the vaginal microbiome in the development of premature labor.
Main Methods:
- Utilized three distinct preterm birth models in preclinical studies.
- Administered intra-amniotic lipopolysaccharide (LPS) and interleukin-1 alpha (IL-1α) to induce labor.
- Blocked progesterone action using RU-486 to assess its impact on labor and microbiome.
- Analyzed inflammatory responses in the amniotic cavity and cervico-vaginal microenvironment.
- Monitored changes in the vaginal microbiome composition and signs of active labor.
Main Results:
- Intra-amniotic LPS induced inflammation, vaginal microbiome changes, and labor.
- Intra-amniotic IL-1α caused moderate amniotic inflammation but significant cervico-vaginal inflammation, microbiome disruption, and labor.
- Progesterone blockade (RU-486) triggered labor and immune responses without altering the vaginal microbiome.
- Preterm labor facilitated the upward movement of cervico-vaginal bacteria into the amniotic cavity irrespective of the initial trigger.
Conclusions:
- Host-microbiome interactions in the cervico-vaginal microenvironment are dynamically involved in premature labor.
- Different stimuli initiate labor through distinct pathways, impacting the microbiome variably.
- The findings provide crucial mechanistic insights into the development of preterm birth, highlighting the importance of the cervico-vaginal microbiome.
Abstract:
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.
