Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

Shiloh R. Lueschow, Jessica Stumphy, Huiyu Gong, Stacy L. Kern, Timothy G. Elgin, Mark Underwood, Karen M. Kalanetra, David A. Mills, Melissa H. Wong, David K. Meyerholz, Misty Good, Steven J. McElroy

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature hostmicrobial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine.

Original languageEnglish (US)
Article numbere0204967
JournalPLoS One
Volume13
Issue number10
DOIs
StatePublished - Oct 1 2018

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Paneth Cells
enterocolitis
Necrotizing Enterocolitis
immatures
mice
Histology
Flow cytometry
cells
Electron microscopy
Microbiota
Animals
Intestines
homeostasis
intestines
Homeostasis
Microbial Interactions
Chemical Models
Klebsiella
Gastrointestinal Microbiome
microbiome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis. / Lueschow, Shiloh R.; Stumphy, Jessica; Gong, Huiyu; Kern, Stacy L.; Elgin, Timothy G.; Underwood, Mark; Kalanetra, Karen M.; Mills, David A.; Wong, Melissa H.; Meyerholz, David K.; Good, Misty; McElroy, Steven J.

In: PLoS One, Vol. 13, No. 10, e0204967, 01.10.2018.

Research output: Contribution to journalArticle

Lueschow, SR, Stumphy, J, Gong, H, Kern, SL, Elgin, TG, Underwood, M, Kalanetra, KM, Mills, DA, Wong, MH, Meyerholz, DK, Good, M & McElroy, SJ 2018, 'Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis', PLoS One, vol. 13, no. 10, e0204967. https://doi.org/10.1371/journal.pone.0204967
Lueschow, Shiloh R. ; Stumphy, Jessica ; Gong, Huiyu ; Kern, Stacy L. ; Elgin, Timothy G. ; Underwood, Mark ; Kalanetra, Karen M. ; Mills, David A. ; Wong, Melissa H. ; Meyerholz, David K. ; Good, Misty ; McElroy, Steven J. / Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis. In: PLoS One. 2018 ; Vol. 13, No. 10.
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