Paratuberculosis and Crohn's Disease: Got Milk?
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Paratuberculosis and Crohn's Disease: Got Milk?
Association or Causation?
Just because Crohn's sufferers are much more likely to have MAP found in their gut does not necessarily mean that MAP caused the disease. Another explanation of the finding could be that this is just an opportunistic invasion of MAP into diseased tissue, leading to a chicken and egg scenario of which came first. If MAP just has an affinity for inflamed tissue, however, one would expect that one would also find MAP more frequently in biopsies of similar diseases like ulcerative colitis, but this is not the case. Conversely, if you look for the DNA of other nonspecific mycobacteria, one finds that they are uniformly distributed between Crohn's patients versus controls. This finding is consistent with the known environmental distribution of mycobacteria, which are present in 30-50% of all environmental samplings -- including water, soil, even air. So other mycobacteria people routinely come in contact with, even the closely related Mycobacterium avium subspecies silvaticum, are equally distributed among people whether they have Crohn's disease, or colon cancer, or are completely healthy as one might expect.
In medicine there is a method used to try to prove that a specific pathogen causes a specific disease. The first person to definitively prove that a disease was caused by a particular organism was Robert Koch, who uncovered the bacterial origin of anthrax in 1876. Koch cultured the bacteria from a diseased animal, gave anthrax to a healthy animal by inoculating her or him with a pure culture of the bacilli, and then was able to recover and reculture the bug once again. These experiments fulfilled criteria proposed 36 years earlier by Henle as necessary to establish a causal relation between a specific agent and a specific disease. These criteria are now known as the Koch postulates.
Not only are these experiments arguably unethical, they also can be unreliable in clinical medicine, as other animals may not be susceptible to the same diseases that we are. For example, the case to prove that H. pylori caused ulcers was hindered by animal research, as rats and pigs were tested and seemed to be immune. For this and other reasons, there are some recognized infectious diseases which have never fulfilled Koch's postulates. Leprosy, for example, has still never fulfilled more than one of the four criteria, because it is not possible to culture the culprit bacterium in the laboratory. Nonetheless, Mycobacterium leprae is known to be the cause of leprosy, and leprosy is known to be an infectious disease. So while not absolutely necessary to fulfill Koch's postulates to prove causation, they are the most widely accepted method. So researchers set out to the task and they succeeded -- twice.
Chiodini fed chickens pure cultures of the paratuberculosis bacteria he recovered from the surgically removed intestines of children with Crohn's disease. The chickens then developed an intestinal disease resembling Crohn's. In 1986, a different lab fed infant goats a human strain of paratuberculosis and also found that the bacteria induced a Crohn's-like intestinal disease in the goats. The same strain was then recovered back from all of them. When asked why there continues to be so much resistance against the idea of MAP as a cause of Crohn's disease, Chiodini replied "What you have to realize is that there is a lot of politics in medicine. It's not whether you have the proof of something, but whether or not the medical community wants to accept it."
Because there have been so many other failed attempts to figure out the cause of Crohn's, the medical community is very leery of new proposed causes, especially infectious ones. The gastrointestinal community maintains a healthy skepticism regarding new pathogens as the cause of Crohn's disease, because different pathogens suspected in the past, such as chlamydia and measles, have since been disproven. Of all the pathogens once thought associated with Crohn's in the 80 years it's been researched, MAP is the only one directly cultured and the only one capable of causing pathologically indistinguishable disease in other animals.
The way that doctors test for the presence or absence of many infectious diseases is by looking for specific antibodies that our immune system uses to target the invader. When we test for HIV, for example, we are not usually testing for the virus directly, we are looking for the presence of anti-HIV antibodies. If they're found, we can be relatively certain the person has been exposed to HIV. Similar searches have been launched for anti-MAP antibodies. Unfortunately, scientists have had difficulty finding an antibody which is specific for MAP. There are some promising new suspects, however, which are thought to be unique to MAP and have been found in 90% of Crohn's patients, but in less than ten percent of those with ulcerative colitis. These results not only support the theory, but open new research frontiers. A vaccine might be developed and the diagnosis of Crohn's may soon be just a blood test away.
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