Normal pregnancy represents a unique, transient, and dynamic state of altered anatomy, physiology, and immune function. Preterm birth, i.e., before 37 weeks of gestation, occurs in approximately 11% of pregnancies and is the leading cause of neonatal death. In both term and preterm pregnancies, the interplay between the microbiota and the host remains poorly understood. The human indigenous microbial communities (microbiota) play critical roles in health and may be especially important for mother and fetus during pregnancy. We are interested in understanding how the microbiome helps to shape maternal health and fetal development during pregnancy, and how pregnancy shapes the microbiome.

In a 2015 study, using a case-control cohort of 40 women, we characterized weekly variation in the vaginal, gut, and oral microbiota during and after pregnancy. Microbiota membership remained relatively stable at each body site during pregnancy. An altered vaginal microbial community was associated with preterm birth; this finding was corroborated by an analysis of samples from an additional cohort of nine women. We also discovered an abrupt change in the vaginal microbiota at delivery that persisted in some cases for at least 1 year. Our findings suggest that pregnancy outcomes might be predicted by features of the microbiota early in gestation, and serve as the basis for ongoing further investigations.

Multiomics Modeling of the Immunome, Transcriptome, Microbiome, Proteome, and Metabolome Adaptations During Human Pregnancy

Mohammad Sajjad Ghaemi, Daniel B DiGiulio, Kévin Contrepois, Benjamin Callahan, Thuy Ngo, Brittany Lee-McMullen, Benoit Lehallier, Anna Robaczewska, David Mcilwain, Yael Rosenberg-Hasson, Ronald J Wong, Cecele Quaintance, Anthony Culos, Natalie Stanley, Athena Tanada, Amy Tsai, Dyani Gaudilliere, Edward Ganio, Xiaoyuan Han, Kazuo Ando, Leslie McNeil, Martha Tingle, Paul Wise, Ivana Maric, Marina Sirota, Tony Wyss-Coray, Virginia D Winn, Maurice L Druzin, Ronald Gibbs, Gary L Darmstadt, David B Lewis, Vahid Partovi Nia, Bruno Agard, Robert Tibshirani, Garry Nolan, Michael P Snyder, David A Relman, Stephen R Quake, Gary M Shaw, David K Stevenson, Martin S Angst, Brice Gaudilliere, Nima Aghaeepour (2018) Bioinformatics

Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women

Benjamin J. Callahan, Daniel B. DiGiulio, Daniela S. Aliaga Goltsman, Christine L. Sun, Elizabeth K. Costello, Pratheepa Jeganathan, Joseph R. Biggio, Ronald J. Wong, Maurice L. Druzin, Gary M. Shaw, David K. Stevenson, Susan P. Holmes, and David A. Relman (2017) PNAS.

[Anaylsis Files hosted at Stanford Digital Repository]

Temporal and spatial variation of the human microbiota during pregnancy

DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, Sun CL, Goltsman DSA, Wong RJ, Shaw G, Stevenson Dk, Holmes SP, and Relman DA (2016) PNAS.

[Data Files Hosted by SP Holmes]

A microbial perspective of human developmental biology

Mark R. Charbonneau, Laura V. Blanton, Daniel B. DiGiulio, David A. Relman, Carlito B. Lebrilla, David A. Mills, Jeffrey I. Gordon (2016) Nature.