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Microecology, intestinal epithelial barrier and necrotizing enterocolitis

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Abstract

Soon after birth, the neonatal intestine is confronted with a massive antigenic challenge of microbial colonization. Microbial signals are required for maturation of several physiological, anatomical, and biochemical functions of intestinal epithelial barrier (IEB) after birth. Commensal bacteria regulate intestinal innate and adaptive immunity and provide stimuli for ongoing repair and restitution of IEB. Colonization by pathogenic bacteria and/or dysmature response to microbial stimuli can result in flagrant inflammatory response as seen in necrotizing enterocolitis (NEC). Characterized by inflammation and hemorrhagic–ischemic necrosis, NEC is a devastating complication of prematurity. Although there is evidence that both prematurity and presence of bacteria, are proven contributing factors to the pathogenesis of NEC, the molecular mechanisms involved in IEB dysfunction associated with NEC have begun to emerge only recently. The metagenomic advances in the field of intestinal microecology are providing insight into the factors that are required for establishment of commensal bacteria that appear to provide protection against intestinal inflammation and NEC. Perturbations in achieving colonization by commensal bacteria such as premature birth or hospitalization in intensive care nursery can result in dysfunction of IEB and NEC. In this article, microbial modulation of functions of IEB and its relationship with barrier dysfunction and NEC are described.

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Abbreviations

IEB:

Intestinal epithelial barrier

NEC:

Necrotizing enterocolitis

IM:

Intestinal microecology

GALT:

Gut-associated lymphoid tissue

IEL:

Intestinal epithelial lymphocyte

PRRs:

Pattern recognition receptors

MAMPs:

Microbial-associated molecular patterns

TLR:

Toll-like receptor

NOD:

Nucleotide-binding oligomerization domain

FPRs:

Formylated peptide receptors

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

NFκB:

Nuclear factor kappa B

Rel:

Proteins coded by rel oncogenes

M-cells:

Microfold-cells

CARD:

Caspase recruitment domain

Myd88:

Myeloid differentiation primary-response gene 88

T-reg:

T regulatory

Th:

T helper

APRIL:

A proliferation-inducing ligand

BAFF:

B-cell activating factor

SLP1:

Secretory leucocyte peptidase inhibitor 1

AMP:

Antimicrobial peptide

CXC:

Chemokine

IRAK:

IL-1-R associated protein kinase

TNF-α:

Tumor necrosis factor-α

NO:

Nitric oxide

IL:

Interleukin

DGGE:

Denaturing gradient gel electrophoresis

PCR-TTGE:

Polymerase chain reaction-temporal temperature gradient gel electrophoresis

rRNA:

Ribosomal RNA

ARISA:

Automated ribosomal intergenic spacer analysis

FISH:

Fluorescent in situ hybridization

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Acknowledgments

This work was supported by the National Institute of Health grant 1RO1 HD059143-01.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, University of Florida at Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA

    Renu Sharma

  2. Department of Surgery, University of Florida at Jacksonville, Jacksonville, USA

    Joseph J. Tepas III

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  1. Renu Sharma
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  2. Joseph J. Tepas III
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Correspondence to Renu Sharma.

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Sharma, R., Tepas, J.J. Microecology, intestinal epithelial barrier and necrotizing enterocolitis. Pediatr Surg Int 26, 11–21 (2010). https://doi.org/10.1007/s00383-009-2536-2

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