Removal of the cecum affects intestinal fermentation, enteric bacterial community structure, and acute colitis in mice

Abstract

ABSTRACTThe murine cecum is a major site of fermentation of dietary materials, and production of short chain fatty acids (SCFAs). To examine the role that the cecum plays in acute bacterial infection in mice, the cecum was surgically removed, and changes in bacterial communities and production of SCFAs were analyzed relative to surgical sham animals. To incite bacterial colitis, mice were orally challenged with Citrobacter rodentium. The impact of butyrate administered directly into the colon was also examined. Concentrations of SCFAs in feces were substantially lower in mice with an excised cecum. Bacterial communities were also less diverse in cecectomized mice, and densities of major SCFA-producing taxa including bacteria within the Ruminococcaceae and Lachnospiraceae families were reduced. Colonization of the intestine by C. rodentium was not affected by removal of the cecum, and the bacterium equally incited acute colitis in mice with and without a cecum. However, cecectomized mice exhibited lower body weights at later stages of infection indicating an impaired ability to recover following challenge with C. rodentium. Furthermore, removal of the cecum altered immune and inflammatory responses to infection including increased inflammatory markers in the proximal colon (Tnfα, Il10, βd1), and heightened inflammatory response in the proximal and distal colon (Ifnγ, Tnfα, Relmβ). Exogenous administration of butyrate was insufficient to normalize responses to C. rodentium in cecectomized mice. The murine cecum plays a critical role in maintaining intestinal health, and the murine cecectomy model may be a useful tool in elucidating key aspects of intestine-pathogen-microbiota interactions.