Host-microbiome interactions in distinct subsets of preterm labor and birth
Jose Galaz,
Roberto Romero,
Jonathan M. Greenberg,
Kevin R. Theis,
Marcia Arenas-Hernandez,
Yi Xu,
Marcelo Farias-Jofre,
Derek Miller,
Tomi Kanninen,
Valeria Garcia-Flores,
Nardhy Gomez-Lopez
Affiliations
Jose Galaz
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
Roberto Romero
Pregnancy 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; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA; Corresponding author
Jonathan M. Greenberg
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Kevin R. Theis
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Marcia Arenas-Hernandez
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Yi Xu
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Marcelo Farias-Jofre
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
Derek Miller
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA
Tomi Kanninen
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
Valeria Garcia-Flores
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA
Nardhy Gomez-Lopez
Pregnancy 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; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Corresponding author
Summary: 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.
