Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium
Authors: McKee Kimberly , Bassis Christine M. , Golob Jonathan , Palazzolo Beatrice , Sen Ananda , Comstock Sarah S. , Rosas-Salazar Christian , Stanford Joseph B. , O’Connor Thomas , Gern James E. , Paneth Nigel , Dunlop Anne L. ,   ECHO Cohort Consortium, Smith P. Brian , Newby L. Kristin , Adair Linda , Jacobson Lisa P. , Catellier Diane , McGrath Monica , Douglas Christian , Duggal Priya , Knapp Emily , Kress Amii , Blackwell Courtney K. , Mansolf Maxwell A. , Lai Jin-Shei , Ho Emily , Cella David , Gershon Richard , Macy Michelle L. , Das Suman R. , Freedman Jane E. , Mallal Simon A. , McLean John A. , Shah Ravi V. , Shilts Meghan H. , Alshawabkeh Akram N. , Cordero Jose F. , Meeker John , Trasande Leonardo , Camargo Carlos A. , Hasegawa Kohei , Zhu Zhaozhong , Sullivan Ashley F. , Dabelea Dana , Perng Wei , Bekelman Traci A. , Wilkening Greta , Magzamen Sheryl , Moore Brianna F. , Starling Anne P. , Rinehart Deborah J. , Mitchell Daphne Koinis , D’Sa Viren , Deoni Sean C. L. , Mueller Hans-Georg , Duarte Cristiane S. , Monk Catherine , Canino Glorisa , Posner Jonathan , Murray Tenneill , Lugo-Candelas Claudia , Dunlop Anne L. , Brennan Patricia A. , Hockett Christine , Elliott Amy , Ferrara Assiamira , Croen Lisa A. , Hedderson Monique M. , Ainsworth John , Bacharier Leonard B. , Bendixsen Casper G. , Gern James E. , Gold Diane R. , Hartert Tina V. , Jackson Daniel J. , Johnson Christine C. , Joseph Christine L. M. , Kattan Meyer , Hershey Gurjit K. Khurana , Lemanske Robert F. , Lynch Susan V. , Miller Rachel L. , O’Connor George T. , Ober Carole , Ownby Dennis , Rivera-Spoljaric Katherine , Ryan Patrick H. , Seroogy Christine M. , Singh Anne Marie , Wood Robert A. , Zoratti Edward M. , Habre Rima , Farzan Shohreh , Gilliland Frank D. , Hertz-Picciotto Irva , Bennett Deborah H. , Schweitzer Julie B. , Schmidt Rebecca J. , LaSalle Janine M. , Hipwell Alison E. , Keenan Kate E. , Karr Catherine J. , Bush Nicole R. , LeWinn Kaja Z. , Sathyanarayana Sheela , Zhao Qi , Tylavsky Frances , Carroll Kecia N. , Loftus Christine T. , Leve Leslie D. , Ganiban Jody M. , Neiderhiser Jenae M. , Weiss Scott T. , Litonjua Augusto A. , McEvoy Cindy T. , Spindel Eliot R. , Tepper Robert S. , Newschaffer Craig J. , Lyall Kristen , Volk Heather E. , Landa Rebecca , Ozonoff Sally , Piven Joseph , Hazlett Heather , Pandey Juhi , Schultz Robert , Dager Steven , Botteron Kelly , Messinger Daniel , Stone Wendy , Ames Jennifer , O’Connor Thomas G. , Miller Richard K. , Oken Emily , Hacker Michele R. , James-Todd Tamarra , O’Shea T. Michael , Fry Rebecca C. , Frazier Jean A. , Singh Rachana , Rollins Caitlin , Montgomery Angela , Vaidya Ruben , Joseph Robert M. , Washburn Lisa K. , Gogcu Semsa , Bear Kelly , Rollins Julie V. , Hooper Stephen R. , Taylor Genevieve , Jackson Wesley , Thompson Amanda , Daniels Julie , Hernandez Michelle , Lu Kun , Msall Michael , Lenski Madeleine , Obeid Rawad , Pastyrnak Steven L. , Jensen Elizabeth , Sakai Christina , Santos Hudson , Kerver Jean M. , Paneth Nigel , Barone Charles J. , Elliott Michael R. , Ruden Douglas M. , Fussman Chris , Herbstman Julie B. , Margolis Amy , Schantz Susan L. , Geiger Sarah Dee , Aguiar Andrea , Tabb Karen , Strakovsky Rita , Woodruff Tracey , Morello-Frosch Rachel , Padula Amy , Stanford Joseph B. , Porucznik Christina A. , Giardino Angelo P. , Wright Rosalind J. , Wright Robert O. , Collett Brent , Baumann-Blackmore Nicole , Gangnon Ronald , Jackson Daniel J. , McKennan Chris G. , Wilson Jo , Altman Matt , Aschner Judy L. , Stroustrup Annemarie , Merhar Stephanie L. , Moore Paul E. , Pryhuber Gloria S. , Hudak Mark , Lyndaker Ann Marie Reynolds , Lampland Andrea L. , Rochelson Burton , Jan Sophia , Blitz Matthew J. , Katzow Michelle W. , Brown Zenobia , Chiuzan Codruta , Rafael Timothy , Lewis Dawnette , Meirowitz Natalie , Poindexter Brenda , Gebretsadik Tebeb , Osmundson Sarah , Straughen Jennifer K. , Eapen Amy , Cassidy-Bushrow Andrea , Wegienka Ganesa , Sitarik Alex , Woodcroft Kim , Urquhart Audrey , Levin Albert , Johnson-Hooper Tisa , Davidson Brent , Ma Tengfei , Barrett Emily S. , Blaser Martin J. , Dominguez-Bello Maria Gloria , Horton Daniel B. , Jimenez Manuel , Rosen Todd , Palomares Kristy , Avalos Lyndsay A. , Zhu Yeyi , Hunt Kelly J. , Newman Roger B. , Bloom Michael S. , Alkis Mallory H. , Roberts James R. , Mumford Sunni L. , Burris Heather H. , DeMauro Sara B. , Yee Lynn M. , Hamvas Aaron , Olidipo Antonia F. , Haddad Andrew S. , Eiland Lisa R. , Spillane Nicole T. , Suri Kirin N. , Fisher Stephanie A. , Goldstein Jeffrey A. , Mithal Leena B. , DeRegnier Raye-Ann O. , Maitre Nathalie L. , Nguyen Ruby H. N. , JaKa Meghan M. , Sidebottom Abbey C. , Paidas Michael J. , Potter JoNell E. , Ruby Natale , Duthely Lunthita , Jayakumar Arumugam , Young Karen , Maldonado Isabel , Miller Meghan , Slaughter Jonathan L. , Keim Sarah A. , Lynch Courtney D. , Venkatesh Kartik K. , Whitworth Kristina W. , Symanski Elaine , Northrup Thomas F. , Mendez-Figueroa Hector , Mosquera Ricardo A. , Karagas Margaret R. , Madan Juliette C. , MacKenzie Debra M. , Lewis Johnnye L. , Rennie Brandon J. , Leventhal Bennett L. , Kim Young Shin , Bishop Somer , Nozadi Sara S. , Luo Li , Lester Barry M. , Marsit Carmen J. , Everson Todd , Loncar Cynthia M. , McGowan Elisabeth C. , Sheinkopf Stephen J. , Carter Brian S. , Check Jennifer , Helderman Jennifer B. , Neal Charles R. , Smith Lynne M. 
Published: May 2024

Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors. After adjustment, lower education, rather than self-identified race, remained a robust predictor of L. iners dominant (CST III) and diverse (CST IV) (OR = 8.44, 95% CI = 4.06–17.6 and OR = 4.18, 95% CI = 1.88–9.26, respectively). In random forest models, we identified specific taxonomic features of host factors, particularly urogenital pathogens associated with pregnancy complications (Aerococcus christensenii and Gardnerella spp.) among other facultative anaerobes and key markers of community instability (L. iners). Sociodemographic factors were robustly associated with vaginal microbiota structure in pregnancy and should be considered as sources of variation in human microbiome studies.