Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium
- University of Michigan, United States
- Montana State University, United States
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 naïve 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.
Data availability
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RNA-seq of human intestinal organoids colonized with E. coli and other immature intestinal tissuesPublicly available at ArrayExpress (accession no. E-MTAB-5801).
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Transcriptional Profiling of human pluripotent stem cells and and derived tissuesPublicly available at ArrayExpress (accession no. E-MTAB-3158).
Article and author information
Author details
Funding
National Institutes of Health (U19AI116482)
- Vincent B Young
National Institutes of Health (U01DK103141)
- Jason R Spence
National Institutes of Health (T32AI007528)
- David R Hill
National Institutes of Health (UL1TR000433)
- David R Hill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animal experiments were approved by the University of Michigan Institutional Animal Care and Use Committee (IACUC; protocol # PRO00006609).
Human subjects: Normal, de-identified human fetal intestinal tissue was obtained from the University of Washington Laboratory of Developmental Biology. Normal, de-identified human adult intestinal issue was obtained from deceased organ donors through the Gift of Life, Michigan. All human tissue used in this work was obtained from non-living donors, was de-identified and was conducted with approval from the University of Michigan IRB (protocol # HUM00093465 and HUM00105750).
Copyright
© 2017, Hill et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium
eLife 6:e29132.
https://doi.org/10.7554/eLife.29132
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