PT - JOURNAL ARTICLE AU - David R. Hill AU - Sha Huang AU - Courtney Fields AU - Disharee Mukherjee AU - Brooke Bons AU - Shrikar Thodla AU - Priya H. Dedhia AU - Alana M. Chin AU - Yu-Hwai Tsai AU - Melinda S. Nagy AU - Thomas Schmidt AU - Seth Walk AU - Vincent B. Young AU - Jason R. Spence TI - Bacterial colonization stimulates a complex physiological response in immature human intestinal epithelium AID - 10.1101/144568 DP - 2017 Jan 01 TA - bioRxiv PG - 144568 4099 - http://biorxiv.org/content/early/2017/05/31/144568.short 4100 - http://biorxiv.org/content/early/2017/05/31/144568.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 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.