Helicobacter infection decreases basal colon inflammation, but increases disease activity in experimental IBD

Abstract

Background: Helicobacter species are best known for their roles in the pathology of gastritis; however, several Helicobacter species also colonize the intestine, and less is known about effects of Helicobacter on the development of intestinal inflammation. To evaluate contributions of Helicobacter in inflammatory bowel disease, we investigated whether and how pre-existing intestinal colonization would affect disease severity and biomarkers of inflammation in experimental IBD. Materials and Methods: Mice were infected with H. muridarum 2 weeks prior to induction of colitis mediated by 3% dextran sulfate (DSS). Disease activity index, stool blood and consistency, colon length, myeloperoxidase, histopathology, blood and lymphatic vessels, and numbers of dilated mucosal crypts were measured in control, DSS-only, H. muridarum-infected, and H. muridarum-infected + DSS mice. Results: Prior to DSS challenge, H. muridarum-infected mice showed little distal gut injury by several indices of colon inflammation with decreased blood vessel density in the submucosa, and lower lymphatic density in the mucosa and submucosa. However, after DSS colitis, H. muridarum-infected mice exhibited significantly greater disease. Weight change, stool bleeding, diarrhea, and angiogenesis were all increased in H. muridarum-infected mice in DSS colitis compared to DSS controls. Conclusions: Our data show that Helicobacter colonization of the intestine, unlike that of the stomach, lowers basal gut inflammatory scores, but increases disease activity and inflammation in an acute colitis model. Intestinal Helicobacter infection may therefore represent a significant sub-clinical factor which predisposes the gut to inflammatory injury.