The bile acid regulation of the intestinal epithelial cell homeostasis during bacterial-induced colitis

 Enteric bacterial infections, such as the human enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively), are of great global health concern. Infections with these enteric pathogens can cause a wide array of clinical symptoms, ranging from ephemeral diarrhea episodes and non-specific gastrointestinal symptoms to severe colitis and serious organ dysfunction. The intestinal epithelial cells (IECs) have intimate contact with a variety of enteric pathogens, microbial metabolites, and immunomodulatory molecules, including bile acids (BAs). The BAs are known to regulate the IECs’ functions in health and disease by modulating apoptotic pathways and enhancing IEC proliferation during intestinal insults. Using a murine model (C57BL/6) of bacterial-induced colitis, we have investigated the roles played by BA signaling during enteric infection with C. rodentium infection. We have found that a functional BA signaling pathway protects IECs from cell death, most likely by modulating the inflammasome and autophagy pathways. Targeting the BA signaling, and autophagy may provide novel approaches for preventing a wide array of chronic intestinal inflammatory conditions such as human inflammatory bowel disease (IBD).