Could Mycobacterium avium subspecies paratuberculosis cause Crohn's disease, ulcerative colitis…and colorectal cancer?

Abstract

Infectious agents are known causes of human cancers. Schistosoma japonicum and Schistosoma mansoni cause a percentage of colorectal cancers in countries where the respective Schistosoma species are prevalent. Colorectal cancer is a complication of ulcerative colitis and colonic Crohn's disease, the two main forms of idiopathic inflammatory bowel disease (IIBD). Mycobacterium avium subspecies paratuberculosis (MAP), the cause of a chronic intestinal disease in domestic and wild ruminants, is one suspected cause of IIBD. MAP may therefore be involved in the pathogenesis of IIBD-associated colorectal cancer as well as colorectal cancer in individuals without IIBD (sporadic colorectal cancer) in countries where MAP infection of domestic livestock is prevalent and MAP's presence in soil and water is extensive. MAP organisms have been identified in the intestines of patients with sporadic colorectal cancer and IIBD when high magnification, oil immersion light microscopy (×1000 total magnification rather than the usual ×400 total magnification) is used. Research has demonstrated MAP's ability to invade intestinal goblet cells and cause acute and chronic goblet cell hyperplasia. Goblet cell hyperplasia is the little-recognized initial pathologic lesion of sporadic colorectal cancer, referred to as transitional mucosa, aberrant crypt foci, goblet cell hyperplastic polyps or transitional polyps. It is the even lesser-recognized initial pathologic feature of IIBD, referred to as hypermucinous mucosa, hyperplastic-like mucosal change, serrated epithelial changes, flat serrated changes, goblet cell rich mucosa or epithelial hyperplasia. Goblet cell hyperplasia is the precursor lesion of adenomas and dysplasia in the classical colorectal cancer pathway, of sessile serrated adenomas and serrated dysplasia in the serrated colorectal cancer pathway, and of flat and elevated dysplasia and dysplasia-associated lesions or masses in IIBD-associated intestinal cancers. MAP's invasion of intestinal goblet cells may result in the initial pathologic lesion of IIBD and sporadic colorectal cancer. MAP's persistence in infected intestines may result in the eventual development of both IIBD-associated and sporadic colorectal cancer.

Keywords: Aberrant foci; Adenomas; Cancerization; Carcinomas; Goblet; Infection; Inflammatory bowel disease; Serrated; Transitional mucosa.

Fig. 1

Goblet cell changes in Citrobacter rodentium infection. a The well-known pathologic features of Citrobacter rodentium infection include crypt elongation, and variation in shape and “depletion” of the apical mucinogen granule compartment of goblet cells. (H&E, original magnification ×200) b Goblet cell hyperplasia is the rarely recognized pathologic feature of the resolving phase of Citrobacter rodentium infection. (PAS, original magnification ×200) Photomicrographs courtesy of Dr. Bruce Vallance