Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease.
Highlights
Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne’s disease, in dairy cows and every other species of mammal in which it has been identified
While other organisms have been identified in the intestines of patients with Crohn’s disease [23], no other putative pathogenic organism causes a chronic granulomatous inflammation of the intestines in every other species in which it is present. ‘‘For MAP in this situation not to contribute to pathogenesis and merely to have a bystander role, it would be necessary to accept that despite its specific ability to cause chronic inflammation of the intestine in so many animals, including primates, it is somehow harmless to man’’ [24]
If Crohn’s disease is caused by MAP, like other mycobacterial species that cause human disease, large numbers of MAP organisms might be present in some of the histologic lesions of Crohn’s disease, organisms that because of their presence in large numbers could be seen under the microscope, if only we looked in the right places
Summary
Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne’s disease, in dairy cows and every other species of mammal in which it has been identified. If some patients with Crohn’s disease might have pluribacillary MAP infection, i.e., if some of their histologic lesions might have large numbers of MAP organisms, and if MAP might be present within endothelial cells lining lymphatic and vascular walls, two kinds of places where no one has yet looked for them by either direct or indirect methods might have abundant MAP organisms—places where there are large blood vessels or lymphatics and places where there many small blood vessels or lymphatics.
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