Microbiota manipulation to increase macrophage IL-10 improves colitis and limits colitis-associated colorectal cancer
Daniel Fernando Zegarra Ruiz, Dasom V. Kim, Kendra Norwood, Fatima B. Saldana-Morales, Myunghoo Kim, Charles Ng, Ryann Callaghan, Maisha Uddin, Lin-Chun Chang, Randy Longman, Gretchen E. Diehl
Abstract
Inflammatory bowel disease (IBD) is a chronic life-long inflammatory disease affecting almost 2 million Americans. Although new biologic therapies have been developed, the standard medical treatment fails to selectively control the dysregulated immune pathways involved in chronic colonic inflammation. Further, IBD patients with uncontrolled colonic inflammation are at a higher risk for developing colorectal cancer (CRC). Intestinal microbes can impact many immune functions, and here we asked if they could be used to improve intestinal inflammation. By utilizing an intestinal adherent E. coli that we find increases IL-10 producing macrophages, we were able to limit intestinal inflammation and restrict tumor formation. Macrophage IL-10 along with IL-10 signaling to the intestinal epithelium were required for protection in both inflammation and tumor development. Our work highlights that administration of immune modulating microbes can improve intestinal outcomes by altering tissue inflammation.