A Model of Piroxicam-Accelerated Enterocolitis in Interleukin-10 Knockout Mice for Studying Inflammation-Induced Metabolic Alterations

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract affecting over 10 million individuals globally. While substantial research has focused on the immunologic mechanisms and consequences underlying IBD, less is understood about how mucosal inflammation contributes to metabolic dysregulation, including weight loss and reduced appetite. Here, the authors describe a mouse model of piroxicam-accelerated enterocolitis in interleukin-10-knockout (IL-10-KO) mice to study inflammation-induced metabolic dysregulation. IL-10-KO mice are known to develop spontaneous enterocolitis and have heightened susceptibility to enterocolitis triggered by infections or drugs. However, vivarium conditions and strain background have been reported as confounders in colitis development in this model. Piroxicam, a non-steroidal anti-inflammatory drug (NSAID), has been demonstrated to trigger or accelerate enterocolitis in animal models by increasing mucosal exposure to luminal bacteria. In this protocol, male and female IL-10-KO mice were fed a piroxicam-fortified diet in place of a regular chow diet. Food intake and body weight were measured daily to reflect whole-body metabolic alterations, along with clinical manifestations of enterocolitis such as diarrhea and rectal bleeding. The protocol is efficient and reproducible, inducing enterocolitis simultaneously in multiple mice, and allows assessment of metabolic dysregulation in an inflammatory bowel disease model. Further studies using this protocol may investigate the effects of enterocolitis on other components of metabolic dysregulation, such as energy expenditure and body composition, revealing broader connections between inflammatory bowel disease and host metabolism.