Maternal-Fetal Microbiome

About the Program

The Maternal-Fetal Microbiome Unit focuses on the application of molecular microbiology techniques and bioinformatics to identify the roles of microorganisms in adverse pregnancy outcomes, especially spontaneous preterm birth. We are particularly interested in the dynamic interactions between microbiomes and host immunity in the vagina and intra-amniotic environment during pregnancy. Through participation in the Unit’s research, Maternal-Fetal Fellows gain hands-on experience in contemporary microbiome approaches, including automated high-throughput DNA extraction, next-generation sequencing technologies, comparative genomics, and multivariate data analysis.

Objectives

  • To comprehensively and accurately characterize the human perinatal microbiome throughout gestation
  • To identify and manage microbial etiologies of the great obstetrical syndromes, especially preterm labor with intact membranes and preterm prelabor rupture of membranes
  • To train Medical and Postdoctoral Fellows in the latest molecular microbiology techniques

Research Focus

  • Elucidating how specific elements of the microbiome interact with immune mediators in the human reproductive tract
  • Determining the extent of clinically-relevant variation in the pangenomes of key members of the vaginal microbiome
  • Evaluating whether, and if so how, variation in the vaginal microbiome translates to the likelihood of spontaneous preterm birth
  • Capitalizing on comparative genomics of the vaginal microbiome to identify virulence factors promoting microbial invasion of the amniotic cavity

Highlights

  • Demonstrated that the human placenta does not have a microbial signal beyond that also evident in background technical controls in typical pregnancies.
  • Using nonhuman primate and mouse models, further demonstrated that the mammalian fetus is not colonized by microbial communities in utero.
  • Efficaciously characterized the molecular microbiology of the human upper genital tract outside pregnancy and demonstrated that the endometrium is not dominated by Lactobacillus, as has been widely reported.
  • Showed that the majority of bacteria associated with intra-amniotic infection ascended into the amniotic cavity from the lower genital tract.

Selected Publications

  • Theis KR, Romero R, Winters AD, Jobe AH, Gomez-Lopez N. Lack of evidence for microbiota in the placental and fetal tissues of rhesus macaques. mSphere. 2020; 5(3):e00210- 20. doi: 10.1128/mSphere.00210-20.
  • Theis KR, Romero R, Greenberg JM, Winters AD, Garcia-Flores V, Motomura K, Ahmad MA, Galaz J, Arenas-Hernandez M, Gomez-Lopez N. No consistent evidence for microbiota in murine placental and fetal tissues. mSphere. 2020; 5(1):e00933-19. doi: 10.1128/mSphere.00933-19.
  • Theis KR, Romero R, Motomura K, Galaz J, Winters AD, Pacora P, Miller D, Slutsky R, Florova V, Levenson D, Para R, Varrey A, Kacerovsky M, Hsu C-D, Gomez-Lopez N. Microbial burden in inflammasome activation in amniotic fluid of patients with preterm prelabor rupture of membranes. Journal of Perinatal Medicine. 2020; 48(2):115-131. doi: 10.1515/jpm-2019-0398.
  • Romero R, Gomez-Lopez N, Winters AD, Jung E, Shaman M, Bieda J, Panaitescu B, Pacora P, Erez O, Greenberg JM, Ahmad MM, Hsu C-D, Theis KR. Evidence that intra-amniotic infections are often the result of an ascending invasion – a molecular microbiological study. Journal of Perinatal Medicine. 2019; 47(9):915-931. doi: 10.1515/jpm-2019-0297.
  • Winters AD, Romero R, Gervasi MT, Gomez-Lopez N, Tran MR, Garcia-Flores V, Pacora P, Jung E, Hassan SS, Hsu C-D, Theis KR. Does the endometrial cavity have a molecular microbial signature? Scientific Reports. 2019; 9:9905. doi: 10.1038/s41598-019-46173-0.
  • Theis KR, Romero R, Winters AD, Greenberg JM, Gomez-Lopez N, Alhousseini A, Bieda J, Maymon E, Pacora P, Fettweis JM, Buck GA, Jefferson KK, Strauss III JF, Erez O, Hassan SS. Does the human placenta delivered at term have a microbiota? Results of cultivation, quantitative real-time PCR, 16S rRNA gene sequencing, and metagenomics. American Journal of Obstetrics and Gynecology. 2019; 220:267.e1-39. doi: 10.1016/j.ajog.2018.10.018.

Distinguished Faculty

 

Kevin R. Theis, PhD

Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, and the Perinatology Research Branch, NICHD/NIH/DHHS

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