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Elife. 2017 Nov 7;6. pii: e29132. doi: 10.7554/eLife.29132.

Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium.

Author information

1
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, United States.
2
Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, United States.
3
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, United States.
4
Department of Surgery, University of Michigan, Ann Arbor, United States.
5
Department of Microbiology and Immunology, Montana State University, Bozeman, United States.
6
Department of Cell andDevelopmental Biology, University of Michigan, Ann Arbor, United States.
#
Contributed equally

Abstract

The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine.

KEYWORDS:

E. coli; developmental biology; epithelial barrier function; human; infectious disease; innate defense; intestinal epithelium; microbiology; microbiota; neonatal intestinal colonization; stem cells

PMID:
29110754
PMCID:
PMC5711377
DOI:
10.7554/eLife.29132
[Indexed for MEDLINE]
Free PMC Article

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