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Previously, we reported that orally administered Emu Oil (EO) increases mucosal thickness in the small intestine and colon in rodent models of chemotherapy-induced mucositis and colitis. However, it remains unclear whether mucosal thickening (crypt and villus lengthening) represents a process of normal or aberrant growth. We sought to determine if villus height (VH) and crypt depth (CD) measurements returned to normal in EO-treated rats following withdrawal of EO therapy. Dark agouti rats ( n = 8/group) were gavaged daily for 10 days with water, olive oil (OO), or EO (0.5 mL or 1 mL). Groups of rats were euthanized on days 10 and 17. Intestinal weights, lengths, VH, and CD were quantified. P &lt; 0.05 was considered significant. On day 10, jejuno–ileum weight was increased by OO (26%) and EO (0.5 mL: 15%; 1 mL: 29%) compared to water controls ( P &lt; 0.01), which was normalized by day 17. On days 10 and 17, jejuno-ileum length was greater in OO- (12%) and EO-treated rats (0.5 mL: 8%; 1 mL: 12%; P &lt; 0.05), relative to water controls. On day 10, OO and EO increased ileal VH (OO: 32%; 0.5 EO: 22%; EO: 35%; P &lt; 0.01) and CD (OO: 17%; 0.5 EO: 13%; EO: 22%) compared to water controls. Importantly, however, after withdrawal of all oils, VH and CD measurements returned to normal control values. Moreover, the VH:CD ratio (potential indicator of dysplasia) remained unchanged in all experimental groups on days 10 and 17. The restoration of normal intestinal architecture following cessation of Emu Oil therapy supports its safety for application in intestinal disorders.    Impact statement   Uncontrolled inflammation and intestinal proliferation can predispose to the development of colorectal cancer. In previous pre-clinical studies, we demonstrated that oral administration of Emu Oil promotes intestinal repair via stimulation of the mucosa in response to tissue injury and inflammation. Therefore, it was important to determine if Emu Oil administration did not promote the precocious development of colorectal cancer. The current study revealed that Emu Oil returned indicators of intestinal proliferation back to normal values after a period of seven days. These data strongly support the safety of Emu Oil for further studies in the context of bowel inflammation.

Intestinal homeostasis is restored in mice following a period of intestinal growth induced by orally administered Emu Oil