As inflammatory bowel diseases (IBD) develop, the host’s homeostatic relationship with their microbiota changes. Early “preclinical” stages of colitis are relatively understudied, especially with respect to host-microbiota interactions. Intestinal epithelial cells (IECs) serve as the primary host interface for host-microbiota interactions, and their functions are achieved through specific transcriptional regulatory programs. Hepatocyte nuclear factor 4 alpha (HNF4A) is a nuclear receptor transcription factor known to regulate IEC development, barrier function, and metabolism.