@article{7ea1891f371641e7a269adf09016a209,
title = "Heritable vaginal bacteria influence immune tolerance and relate to early-life markers of allergic sensitization in infancy",
abstract = "Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy and asthma risk in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) and paired infant stool (n = 172) samples, we identify four compositionally and functionally distinct Lactobacillus-dominated vaginal microbiota clusters (VCs) that relate to prenatal maternal health and exposures and infant serum immunoglobulin E (IgE) status at 1 year. Variance in bacteria shared between mother and infant pairs relate to VCs, maternal allergy/asthma status, and infant IgE levels. Heritable bacterial gene pathways associated with infant IgE include fatty acid synthesis and histamine and tryptophan degradation. In vitro, vertically transmitted Lactobacillus jensenii strains induce immunosuppressive phenotypes on human antigen-presenting cells. Murine supplementation with L. jensenii reduces lung eosinophils, neutrophilic expansion, and the proportion of interleukin-4 (IL-4)+ CD4+ T cells. Thus, bacterial and atopy heritability are intimately linked, suggesting a microbial component of intergenerational disease transmission.",
keywords = "Lactobacillus, asthma, atopy, immune tolerance, inherited bacteria, microbiota, prenatal, transmission, vaginal, vaginal microbiota",
author = "{for the ECHO Children's Respiratory and Environmental Workgroup} and McCauley, {Kathryn E.} and Elze Rackaityte and Brandon LaMere and Fadrosh, {Douglas W.} and Fujimura, {Kei E.} and Panzer, {Ariane R.} and Lin, {Din L.} and Lynch, {Kole V.} and Joanna Halkias and Mendoza, {Ventura F.} and Burt, {Trevor D.} and Casper Bendixsen and Kathrine Barnes and Haejin Kim and Kyra Jones and Ownby, {Dennis R.} and Johnson, {Christine C.} and Seroogy, {Christine M.} and Gern, {James E.} and Boushey, {Homer A.} and Lynch, {Susan V.}",
note = "Funding Information: We greatly appreciate the contributions, time, and continued commitment from participants in the MAAP and WISC studies and tissue donors who made this study possible. We thank the study coordinators and research staff from the WISC and MAAP study sites for their many contributions in establishing these birth cohorts, as well as the data managers who coordinated and harmonized data between cohorts. Non-author contributors from these institutions include: Alex Binder, Eneida A. Mendonca, Laura Ladick, Lisa Gress, and Sweta Singh from the CREW Informatics Core; Alexandra Sitarik, Amanda Cyrus, Anthony Wahlman, Audrey Urquhart, Brent Davidson, Ganesa Wegienka, Katherine Graham McNeil, Kevin Bobbitt, Kimberley Woodcroft, Shirley Zhang, Stacy Bellemore, and Suzanne Havstad from the MAAP cohort; Amy Dresen, Brent F. Olson, Deanna Cole, Deborah Chasman, Elizabeth Armagost, Erin Donnerbauer, Heather Floerke, Irene Ong, Jeffrey J. VanWormer, Jennifer Meece, Kristine Grindle, Matthew C. Keifer, Michael D. Evans, Ronald E. Gangnon, Rose Vrtis, Tammy Kronenwetter Koepel, Tara Johnson, Terry Foss, Tressa Pappas, Vicki Moon, Wayne Frome, Yury Bochkov from the WISC cohort. We especially thank Edward M. Zoratti, a co-PI of MAAP, for support of the project. Research reported in this publication was supported by the CREW consortium, Office of the Director, National Institutes of Health under award 5UH3 OD023282. E.R. was supported by NSF Graduate Research Fellowship grant 1650113 and by the NIAID F31AI136336 award. J.H. was supported by NIAID grant K08 AI128007. T.D.B. was supported by an award from the Burroughs Wellcome Fund Preterm Birth Initiative. C.B. was supported by CTSA grant UL1 TR002373 NIH-ICTR. D.R.O. was supported by NIH award 5P01AI089473-07. J.E.G was supported by NIH/NIAID award 5U19AI104317. We acknowledge the PFCC (RRID: SCR_018206), supported in part by grant NIH P30 DK063720 and by NIH S10 Instrumentation Grant S10 1S10OD021822-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. K.E.M. E.R. C.C.J. C.M.S. J.E.G. and S.V.L. designed the study. C.B. K.B. H.K. and K.J. coordinated sample collection within each study site. E.R. B.L. D.W.F. K.E.F. A.R.P. and K.V.L. performed sample extraction and 16S rRNA sequencing. K.E.M. and E.R. performed statistical analyses. S.V.L. and E.R. conceptualized and designed microbiological, immunological, and murine studies. E.R. J.H. V.F.M. and T.D.B. assisted with human sample collection. E.R. performed microbiological, immunological, and murine studies, A.R.P. and D.L.L. assisted with murine studies. K.E.M. E.R. and S.V.L. wrote the manuscript. D.R.O. C.C.J. C.M.S. H.A.B. and J.E.G. reviewed the manuscript and provided significant contributions toward its direction. J.E.G. is a paid consultant for AstraZeneca, Meissa Vaccines Inc. and Gossamer Bio and has stock options in Meissa Vaccines Inc. H.A.B. serves on a scientific advisory committee for Siolta Therapeutics Inc. S.V.L. is a co-founder and member of the board and consults for and holds stock options in Siolta Therapeutics Inc.; she also consults for Solarea Bio. The Regents of UCSF have filed a patent application (PCT/US2019/045,354) on behalf of S.V.L. and E.R. relating to the methods and compositions of fetal bacteria. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper received support from a program designed to increase minority representation in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: We greatly appreciate the contributions, time, and continued commitment from participants in the MAAP and WISC studies and tissue donors who made this study possible. We thank the study coordinators and research staff from the WISC and MAAP study sites for their many contributions in establishing these birth cohorts, as well as the data managers who coordinated and harmonized data between cohorts. Non-author contributors from these institutions include: Alex Binder, Eneida A. Mendonca, Laura Ladick, Lisa Gress, and Sweta Singh from the CREW Informatics Core; Alexandra Sitarik, Amanda Cyrus, Anthony Wahlman, Audrey Urquhart, Brent Davidson, Ganesa Wegienka, Katherine Graham McNeil, Kevin Bobbitt, Kimberley Woodcroft, Shirley Zhang, Stacy Bellemore, and Suzanne Havstad from the MAAP cohort; Amy Dresen, Brent F. Olson, Deanna Cole, Deborah Chasman, Elizabeth Armagost, Erin Donnerbauer, Heather Floerke, Irene Ong, Jeffrey J. VanWormer, Jennifer Meece, Kristine Grindle, Matthew C. Keifer, Michael D. Evans, Ronald E. Gangnon, Rose Vrtis, Tammy Kronenwetter Koepel, Tara Johnson, Terry Foss, Tressa Pappas, Vicki Moon, Wayne Frome, Yury Bochkov from the WISC cohort. We especially thank Edward M. Zoratti, a co-PI of MAAP, for support of the project. Research reported in this publication was supported by the CREW consortium, Office of the Director, National Institutes of Health under award 5UH3 OD023282 . E.R. was supported by NSF Graduate Research Fellowship grant 1650113 and by the NIAID F31AI136336 award. J.H. was supported by NIAID grant K08 AI128007 . T.D.B. was supported by an award from the Burroughs Wellcome Fund Preterm Birth Initiative. C.B. was supported by CTSA grant UL1 TR002373 NIH-ICTR. D.R.O. was supported by NIH award 5P01AI089473-07 . J.E.G was supported by NIH/ NIAID award 5U19AI104317 . We acknowledge the PFCC (RRID: SCR_018206 ), supported in part by grant NIH P30 DK063720 and by NIH S10 Instrumentation Grant S10 1S10OD021822-01 . 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: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = aug,
day = "16",
doi = "10.1016/j.xcrm.2022.100713",
language = "English (US)",
volume = "3",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "8",
}