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MAP & CROHN'S DISEASE

MAP and Crohn’s Disease

 

Crohn's disease[1] (CD) is an inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from anus to mouth, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody), vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis and inflammation of the eye.

CD is an immune-deficient disease, and it is classified as a type of inflammatory bowel disease. There has been evidence of a genetic link to CD, putting individuals with siblings afflicted with the disease at higher risk. It is understood to have a large environmental component as evidenced by the higher number of cases in western industrialized nations. Males and females are equally affected. Smokers are three times more likely to develop CD. CD affects over 2,000,000 people in North America.

 Prevalence estimates for Northern Europe have ranged from 27–48 per 100,000. Crohn's disease tends to present initially in the teens and twenties, with another peak incidence in the fifties to seventies, although the disease can occur at any age. 

Similar to Johne’s Disease in cattle, no known pharmaceutical or surgical cure for Crohn's disease currently exists for humans. Furthermore, new discoveries of MAP have been found in human patients and we believe that individuals that are genetically predisposed could possibly be contracting the disease through digestion of MAP- infected milk.

An overwhelming number of studies point to a relation between Johne’s disease and Crohn’s. 80% of the patients with Crohn’s are positive for Mycobacterium Paratubercolosis (MAP) infection when examined by intestinal biopsy. (Fouad A. K. El-Zaataria, Michael S. Osatob and David Y. Graham, a Inflammatory Bowel Disease Laboratory, Veterans Affairs Medical Center and Department of Medicine, Baylor College of Medicine, 2002 Holcombe Blvd, Rm 3A-320, Houston, TX 77030, USA)
Drinking milk from cows infected with Johne’s disease is one way people are exposed to paratuberculosis infection. Milk is the focus of exposure because cows with Johne's disease secrete MAP abundantly in their milk. Milk studies done in Europe, among them a study from Switzerland in 2003, where 1,384 bulk milk samples from different regions were tested for M. paratuberculosis using DNA probe methods, show that 19.7 percent were positive for the bacteria. Intriguingly, the cows from Swiss farms were predominantly asymptomatic – they were apparently ill, but not producing the massive diarrhea that characterizes the latter stages of M. paratuberculosis infection. MAP can be excreted into milk and colostrum in both clinically and sub-clinically infected cows. Raw milk may also be contaminated with feces during the milking process (Clarke 1997). One study has estimated that the average fecal contamination of raw milk is 10 mg of feces per liter of milk (reviewed by Rubery 2002). Feces can contain at least 106 colony forming units per gram, indicating that fecal contamination of milk may be a critical point at which MAP can enter the food supply. 

 

It is also possible that water sources may be contaminated with MAP through the excreta of infected animals (ruminant and non-ruminant). Water running off from grazing lands, or lands that have used manure from infected animals as fertilizer, may therefore contain viable MAP (Aronson et al. 1999; Grant et al. 2001; When et al. 2001). 

MAP has been shown to be able to survive some community water treatment methods currently in place in the UK and USA (Mishanga et al. 1996). MAP  has been detected in potable water supplies and has been documented as a source of mycobacteria infection of immunocompromised hosts (Aronson et al. 1999). Thus it is possible that MAP is present in potable water supplies. 

Dr. Rodrick Chiodini, at Brown University demonstrated that m. paratuberculosis sheds its cell wall in humans, and takes a new form, called a spheroblast. In a landmark study, Dr. Chiodini cultured Mycobacteria from children infected with Crohn's. 

Further establishing the causative link, M. paratuberculosis isolated from Crohn's patients was found to cause a similar disease when fed to farm animals. It is therefore evident that individuals that are genetically predisposed can be contracting the disease through digestion of Johne’s disease –infected milk.

 

 

 

How MAP triggers Crohn’s Disease

Muramyldipeptides (MDP), released from peptidoglycans constituting the mycobacterial cell walls, are potent immunomodulators and are known triggers of inflammation. MDP increases the synthesis of tumour necrosis factor and triggers the proinflammatory cytokine cascade. The protein NOD2 is able to recognize and bind MDP. Cells with a defective NOD2 gene cannot bind MDP to the necessary extent. This increases the disposition to develop Crohn’s disease at least in a proportion of patients. Peptidoglycans in the cell wall of different bacteria are associated with several inflammatory diseases. MDP has a direct effect on inflammation, but it also affects innate immunity in the perinatal period. The sensitization of T cells, epigenetic changes and modulation of apoptosis are often mentioned as effects of MDP. These pathways participate in the pathogenesis of Crohn’s disease and some autoimmune diseases. When a human meets MDP for the first time, the number of MDP molecules which participate in this meeting, the origin of the MDP and how long the meeting takes place seem to be crucial factors. The subsequent meetings of the host with MDP also play an important role. The most important sources of MAP and other mycobacteria are foodstuffs and drinking and surface waters. Mycobacteria can promote the formation of lesions after a long time when a host is stressed or as a result of a booster effect of MDP of the same or different origin



 

 

[1] Individuals who have contracted Crohn’s disease also contain the exact bacteria as the animals that contracted Johne’s disease.