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

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

doi:10.1371/journal.pone.0204967

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

Journal article

Open access

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

Steven J Mcelroy, Shiloh R Lueschow, Jessica Stumphy, Huiyu Gong, Stacy L Kern, Timothy G Elgin, Mark A Underwood, Karen M Kalanetra, David A Mills, Melissa H Wong, …

PLoS One, Vol.13(10), pp.e0204967-e0204967

10/01/2018

DOI: 10.1371/journal.pone.0204967

PMCID: PMC6166990

PMID: 30273395

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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 host-microbial 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.

Medical Microbiology

Digestive System

Microbiology

Genomics

Bacteria

Genetics

Anatomy

Cell Biology

Klebsiella

Gastrointestinal Tract

Science

Paneth Cells

Organisms

Microbial Genomics

Bacterial Pathogens

Pathology and Laboratory Medicine

Cell Processes

Cell Death

Research Article

Enterobacteriaceae

Pathogens

Cellular Types

Medicine and Health Sciences

Epithelial Cells

Microbial Pathogens

Epithelium

Medicine

Autophagic Cell Death

Biology and Life Sciences

Biological Tissue

Animal Cells

Microbiome

Small Intestine

Details

Title: Subtitle: Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis
Creators: Steven J Mcelroy
Shiloh R Lueschow
Jessica Stumphy
Huiyu Gong
Stacy L Kern
Timothy G Elgin
Mark A Underwood
Karen M Kalanetra
David A Mills - University of California, Davis
Melissa H Wong
David K Meyerholz
Misty Good
Resource Type: Journal article
Publication Details: PLoS One, Vol.13(10), pp.e0204967-e0204967
DOI: 10.1371/journal.pone.0204967
PMID: 30273395
PMCID: PMC6166990
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK083677; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK097335; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK101608; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK111473; DOI: 10.13039/100000062, name: National Institute of Diabetes and Digestive and Kidney Diseases, award: DK085525; DOI: 10.13039/100000054, name: National Cancer Institute, award: CA060533
Language: English
Date published: 10/01/2018
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Internal Medicine
Record Identifier: 9984083269402771

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