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

ABSTRACT

The 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.

KEYWORDS:

• Cecum
• Cecectomy
• Dysbiosis
• Short Chain Fatty Acids
• Inflammation

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors would like to thank the following individuals at Agriculture and Agri-Food Canada Lethbridge Research and Development Centre: Tara Shelton for overseeing, conducting, or assisting with all aspects of the animal component of the study; Angela Bamra, Paige Fletcher and Kaylie Graham for their assistance with sample collection and animal husbandry; and Toby Entz for experimental design and statistical advice.

Authors’ contributions

G.D.I. conceived the research; K.B., R.R.E.U, and G.D.I. designed the research; G.D.I. obtained ethics approvals; K.B., R.R.E.U., and G.D.I. performed experiments; K.B. and G.D.I. analyzed data; K.B., R.R.E.U, and G.D.I interpreted results of experiments; K.B. and G.D.I. prepared figures; K.B. and G.D.I. generated the initial draft of the manuscript; K.B., D.W.A., R.R.E.U, and G.D.I. edited the manuscript and approved final version of manuscript

Additional information

Funding

This work was funded by grant QFH-11-013 from Alberta Innovates Bio Solutions (AI Bio) and grant 2014H001R from the Alberta Livestock and Meat Agency (ALMA).