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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 languageAmerican English
Pages (from-to)197-209.e5
JournalCell Host and Microbe
Issue number2
StatePublished - 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.


  • epithelium
  • microbiota
  • neonatal immunity
  • neutrophils
  • oral mucosa
  • γδ T cells


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