Under normal conditions butyrate produced by obligate anaerobes (e.g. firmicutes) provides the dominant energy source for colonocytes via β-oxidation and the tricarboxylic acid cycle. Ulcerative Colitis (UC) is an inflammatory bowel disease (IBD) characterized by reduced butyrate metabolism and intestinal epithelial cell (IEC) mitochondria (needed for β-oxidation). Given that nonhealing ulcers in UC are associated with reduced crypt fissioning and branching, we asked whether there was a relationship between mitochondrial deficiency and butyrate-induced crypt branching using colonoid cultures grown from human biopsies.