TY - JOUR
T1 - The composition of human vaginal microbiota transferred at birth affects offspring health in a mouse model
AU - Jašarević, Eldin
AU - Hill, Elizabeth M.
AU - Kane, Patrick J.
AU - Rutt, Lindsay
AU - Gyles, Trevonn
AU - Folts, Lillian
AU - Rock, Kylie D.
AU - Howard, Christopher D.
AU - Morrison, Kathleen E.
AU - Ravel, Jacques
AU - Bale, Tracy L.
N1 - Funding Information:
We thank Mike Humphrys from the Institute for Genome Sciences, Microbiome Service Laboratory at the University of Maryland School of Medicine for 16 S rRNA gene sequencing. We thank Dr. Kevin Brown for assistance with development of the CyTOF antibody panel, Michael Solga and Claude Chew from the University of Virginia School of Medicine with acquisition of single-cell mass cytometry data, and Dr. El-ad David Amir and the Astrolabe platform for technical assistance with CyTOF data analysis. We also thank Dr. Yasmine Cisse and Dr. Hannah Zierden for insightful discussion and critical feedback on the manuscript. Research reported in this publication was supported in part by National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, and the Institute for Nursing Research of the National Institutes of Health under award numbers R33MH104184 (T.L.B.), R37MH108286 (T.L.B.), R01HD097093 (T.L.B.), R01ES028202 (T.L.B.), R01NR014826 (J.R.), R01NR015495 (J.R.), K99HD091376 (K.E.M.), and K01DK121734 (E.J.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.
AB - Newborns are colonized by maternal microbiota that is essential for offspring health and development. The composition of these pioneer communities exhibits individual differences, but the importance of this early-life heterogeneity to health outcomes is not understood. Here we validate a human microbiota-associated model in which fetal mice are cesarean delivered and gavaged with defined human vaginal microbial communities. This model replicates the inoculation that occurs during vaginal birth and reveals lasting effects on offspring metabolism, immunity, and the brain in a community-specific manner. This microbial effect is amplified by prior gestation in a maternal obesogenic or vaginal dysbiotic environment where placental and fetal ileum development are altered, and an augmented immune response increases rates of offspring mortality. Collectively, we describe a translationally relevant model to examine the defined role of specific human microbial communities on offspring health outcomes, and demonstrate that the prenatal environment dramatically shapes the postnatal response to inoculation.
UR - http://www.scopus.com/inward/record.url?scp=85118468339&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26634-9
DO - 10.1038/s41467-021-26634-9
M3 - Article
C2 - 34725359
AN - SCOPUS:85118468339
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6289
ER -