PT  - JOURNAL ARTICLE
AU  - David R. Hill
AU  - Sha Huang
AU  - Melinda S. Nagy
AU  - Veda K. Yadagiri
AU  - Courtney Fields
AU  - Dishari Mukherjee
AU  - Brooke Bons
AU  - Priya H. Dedhia
AU  - Alana M. Chin
AU  - Yu-Hwai Tsai
AU  - Shrikar Thodla
AU  - Thomas M. Schmidt
AU  - Seth Walk
AU  - Vincent B. Young
AU  - Jason R. Spence
TI  - Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium
AID  - 10.1101/144568
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 144568
4099  - http://biorxiv.org/content/early/2017/10/30/144568.short
4100  - http://biorxiv.org/content/early/2017/10/30/144568.full
AB  - 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 diZcult 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.