Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions

Noam Koren; Khaled Zubeidat; Yasmin Saba; Yael Horev; Or Barel; Anneke Wilharm; Oded Heyman; Sharon Wald; Luba Eli-berchoer; Hagit Shapiro; Chen Nadler; Eran Elinav; Asaf Wilensky; Immo Prinz; Hillel Bercovier; Avi Hai Hovav

doi:10.1016/j.chom.2020.12.006

Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions

Noam Koren, Khaled Zubeidat, Yasmin Saba, Yael Horev, Or Barel, Anneke Wilharm, Oded Heyman, Sharon Wald, Luba Eli-berchoer, Hagit Shapiro, Chen Nadler, Eran Elinav, Asaf Wilensky, Immo Prinz, Hillel Bercovier, Avi Hai Hovav^*

^*Corresponding author for this work

Institute of Biomedical Research at the Faculty of Dental Medicine

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Postnatal host-microbiota interplay governs mucosal homeostasis and is considered to have life-long health consequences. The intestine monolayer epithelium is critically involved in such early-life processes; nevertheless, the role of the oral multilayer epithelium remains ill defined. We demonstrate that unlike the intestine, the neonate oral cavity is immensely colonized by the microbiota that decline to adult levels during weaning. Neutrophils are present in the oral epithelium prenatally, and exposure to the microbiota postnatally further recruits them to the preamble neonatal epithelium by γδT17 cells. These neutrophils virtually disappear during weaning as the epithelium seals. The neonate and adult epithelium display distinct turnover kinetics and transcriptomic signatures, with neonate epithelium reminiscent of the signature found in germ-free mice. Microbial reduction during weaning is mediated by the upregulation of saliva production and induction of salivary antimicrobial components by the microbiota. Collectively, unique postnatal interactions between the multilayer epithelium and microbiota shape oral homeostasis. Koren and Zubeidat et al. establish that the oral microbial burden of neonates is higher than adults. Neutrophils recruited in an IL-17-/microbiota-dependent manner defend the permeable neonatal epithelium yet disappear during weaning when the epithelium seals and acquires adult immunological features while, simultaneously, saliva production reduces the microbial load.

Original language	American English
Pages (from-to)	197-209.e5
Journal	Cell Host and Microbe
Volume	29
Issue number	2
DOIs	https://doi.org/10.1016/j.chom.2020.12.006
State	Published - 10 Feb 2021

Bibliographical note

Funding Information:
We thank the Hebrew University Bioinformatics unit (Info-CORE) for Bioinformatics data analysis and the Core Research Facility at the Faculty of Medicine. This work was supported by Israel Science Foundation grant 1418/11 (A.-H.H.). N.K. K.Z. and A.H. designed research. N.K. K.Z. C.N. and A.W. analyzed data. N.K. K.Z. Y.S. O.B. Y.H. A.W. O.H. S.W. L.E.-B. and H.S. performed experiments. H.S. and E.E. contributed to experiments with germ-free mice. A.W. and I.P. contributed to manuscript preparation. A.H. and H.B. wrote the manuscript. The authors declare no financial competing interests. Dr. Eran Elinav serves as on the advisory board of this journal.

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

epithelium
microbiota
neonatal immunity
neutrophils
oral mucosa
γδ T cells

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10.1016/j.chom.2020.12.006

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Koren, N., Zubeidat, K., Saba, Y., Horev, Y., Barel, O., Wilharm, A., Heyman, O., Wald, S., Eli-berchoer, L., Shapiro, H., Nadler, C., Elinav, E., Wilensky, A., Prinz, I., Bercovier, H., & Hovav, A. H. (2021). Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions. Cell Host and Microbe, 29(2), 197-209.e5. https://doi.org/10.1016/j.chom.2020.12.006

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title = "Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions",

abstract = "Postnatal host-microbiota interplay governs mucosal homeostasis and is considered to have life-long health consequences. The intestine monolayer epithelium is critically involved in such early-life processes; nevertheless, the role of the oral multilayer epithelium remains ill defined. We demonstrate that unlike the intestine, the neonate oral cavity is immensely colonized by the microbiota that decline to adult levels during weaning. Neutrophils are present in the oral epithelium prenatally, and exposure to the microbiota postnatally further recruits them to the preamble neonatal epithelium by γδT17 cells. These neutrophils virtually disappear during weaning as the epithelium seals. The neonate and adult epithelium display distinct turnover kinetics and transcriptomic signatures, with neonate epithelium reminiscent of the signature found in germ-free mice. Microbial reduction during weaning is mediated by the upregulation of saliva production and induction of salivary antimicrobial components by the microbiota. Collectively, unique postnatal interactions between the multilayer epithelium and microbiota shape oral homeostasis. Koren and Zubeidat et al. establish that the oral microbial burden of neonates is higher than adults. Neutrophils recruited in an IL-17-/microbiota-dependent manner defend the permeable neonatal epithelium yet disappear during weaning when the epithelium seals and acquires adult immunological features while, simultaneously, saliva production reduces the microbial load.",

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author = "Noam Koren and Khaled Zubeidat and Yasmin Saba and Yael Horev and Or Barel and Anneke Wilharm and Oded Heyman and Sharon Wald and Luba Eli-berchoer and Hagit Shapiro and Chen Nadler and Eran Elinav and Asaf Wilensky and Immo Prinz and Hillel Bercovier and Hovav, {Avi Hai}",

note = "Funding Information: We thank the Hebrew University Bioinformatics unit (Info-CORE) for Bioinformatics data analysis and the Core Research Facility at the Faculty of Medicine. This work was supported by Israel Science Foundation grant 1418/11 (A.-H.H.). N.K. K.Z. and A.H. designed research. N.K. K.Z. C.N. and A.W. analyzed data. N.K. K.Z. Y.S. O.B. Y.H. A.W. O.H. S.W. L.E.-B. and H.S. performed experiments. H.S. and E.E. contributed to experiments with germ-free mice. A.W. and I.P. contributed to manuscript preparation. A.H. and H.B. wrote the manuscript. The authors declare no financial competing interests. Dr. Eran Elinav serves as on the advisory board of this journal. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

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Koren, N, Zubeidat, K, Saba, Y, Horev, Y, Barel, O, Wilharm, A, Heyman, O, Wald, S, Eli-berchoer, L, Shapiro, H, Nadler, C, Elinav, E, Wilensky, A, Prinz, I, Bercovier, H & Hovav, AH 2021, 'Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions', Cell Host and Microbe, vol. 29, no. 2, pp. 197-209.e5. https://doi.org/10.1016/j.chom.2020.12.006

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AU - Koren, Noam

AU - Zubeidat, Khaled

AU - Saba, Yasmin

AU - Horev, Yael

AU - Barel, Or

AU - Wilharm, Anneke

AU - Heyman, Oded

AU - Wald, Sharon

AU - Eli-berchoer, Luba

AU - Shapiro, Hagit

AU - Nadler, Chen

AU - Elinav, Eran

AU - Wilensky, Asaf

AU - Prinz, Immo

AU - Bercovier, Hillel

AU - Hovav, Avi Hai

N1 - Funding Information: We thank the Hebrew University Bioinformatics unit (Info-CORE) for Bioinformatics data analysis and the Core Research Facility at the Faculty of Medicine. This work was supported by Israel Science Foundation grant 1418/11 (A.-H.H.). N.K. K.Z. and A.H. designed research. N.K. K.Z. C.N. and A.W. analyzed data. N.K. K.Z. Y.S. O.B. Y.H. A.W. O.H. S.W. L.E.-B. and H.S. performed experiments. H.S. and E.E. contributed to experiments with germ-free mice. A.W. and I.P. contributed to manuscript preparation. A.H. and H.B. wrote the manuscript. The authors declare no financial competing interests. Dr. Eran Elinav serves as on the advisory board of this journal. Publisher Copyright: © 2020 Elsevier Inc.

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N2 - Postnatal host-microbiota interplay governs mucosal homeostasis and is considered to have life-long health consequences. The intestine monolayer epithelium is critically involved in such early-life processes; nevertheless, the role of the oral multilayer epithelium remains ill defined. We demonstrate that unlike the intestine, the neonate oral cavity is immensely colonized by the microbiota that decline to adult levels during weaning. Neutrophils are present in the oral epithelium prenatally, and exposure to the microbiota postnatally further recruits them to the preamble neonatal epithelium by γδT17 cells. These neutrophils virtually disappear during weaning as the epithelium seals. The neonate and adult epithelium display distinct turnover kinetics and transcriptomic signatures, with neonate epithelium reminiscent of the signature found in germ-free mice. Microbial reduction during weaning is mediated by the upregulation of saliva production and induction of salivary antimicrobial components by the microbiota. Collectively, unique postnatal interactions between the multilayer epithelium and microbiota shape oral homeostasis. Koren and Zubeidat et al. establish that the oral microbial burden of neonates is higher than adults. Neutrophils recruited in an IL-17-/microbiota-dependent manner defend the permeable neonatal epithelium yet disappear during weaning when the epithelium seals and acquires adult immunological features while, simultaneously, saliva production reduces the microbial load.

AB - Postnatal host-microbiota interplay governs mucosal homeostasis and is considered to have life-long health consequences. The intestine monolayer epithelium is critically involved in such early-life processes; nevertheless, the role of the oral multilayer epithelium remains ill defined. We demonstrate that unlike the intestine, the neonate oral cavity is immensely colonized by the microbiota that decline to adult levels during weaning. Neutrophils are present in the oral epithelium prenatally, and exposure to the microbiota postnatally further recruits them to the preamble neonatal epithelium by γδT17 cells. These neutrophils virtually disappear during weaning as the epithelium seals. The neonate and adult epithelium display distinct turnover kinetics and transcriptomic signatures, with neonate epithelium reminiscent of the signature found in germ-free mice. Microbial reduction during weaning is mediated by the upregulation of saliva production and induction of salivary antimicrobial components by the microbiota. Collectively, unique postnatal interactions between the multilayer epithelium and microbiota shape oral homeostasis. Koren and Zubeidat et al. establish that the oral microbial burden of neonates is higher than adults. Neutrophils recruited in an IL-17-/microbiota-dependent manner defend the permeable neonatal epithelium yet disappear during weaning when the epithelium seals and acquires adult immunological features while, simultaneously, saliva production reduces the microbial load.

KW - epithelium

KW - microbiota

KW - neonatal immunity

KW - neutrophils

KW - oral mucosa

KW - γδ T cells

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Maturation of the neonatal oral mucosa involves unique epithelium-microbiota interactions

Abstract

Bibliographical note

Keywords

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