Is Crohn’s disease caused by Mycobacterium avium pseudotuberculosis (MAP)?
In an article out yesterday, Australian Dr. Thomas Borody claims yes, and that the medical community is simply too “stuck in their ways” to admit it. I explain below why I think this is incorrect–or at least, premature.
I mentioned several times in the various AIDS threads and in the prostate cancer/virus thread that it’s often difficult to determine an infectious cause of a so-called “chronic” disease. Not only is there generally a time lag between infection and disease development, but it may be that only certain strains of the microbe cause the disease, or that they only cause the disease in those with certain genetic susceptibilities, or perhaps only in combination with other microbial agents. Chronic disease epidemiology itself is difficult, but tracking infectious causes of these diseases is even more difficult because you’re dealing with a moving target; a virus or bacterium may have evolved so much in the 10 or 20 years (or even 5) from infection to chronic disease development that it’s difficult to do retrospective studies on serology, for example.
New technology is helping. As I mentioned in the prostate cancer post, there are now chips that can contain pieces of up to 20,000 viruses–so we can screen folks for the presence of a host of pathogens, which previously would have taken years and a ton of money. However, this will be most helpful for diseases where the agent is still present. In some diseases, as I mentioned, the agent may no longer be present–the damage is done by the immune system itself, as a reaction to the pathogen.
Additionally, what if similar diseases are caused by more than one agent, either singly or in combination? I used pneumonia as an example in the AIDS post. Imagine pneumonia was a chronic disease–something that developed months or years after exposure to the infectious agent. Since we know pneumonia is caused by 20+ main organisms (plus dozens other minor ones), we’d never see a 1:1 correlation between disease and pathogen if we were doing retrospective studies.
So, keeping that in mind, let’s get to Crohn’s disease. This is an intestinal disease of unknown etiology that affects 380-480,000 people in the U.S. Onset is generally between the ages of 15 and 40, and it often persists for life. It’s more common in women and those of Jewish descent. Though rare in Africa, incidence in the U.S. is similar in Caucasians and African Americans, suggesting an environmental cause (possibly coupled with genetic susceptibility).
There are a number of lines of evidence that do, indeed, point to an infectious cause, which was first hypothesized almost 100 years ago. MAP–a species of mycobacterium that’s kind of a cousin to those which cause tuberculosis and leprosy–causes a similar disease similar to Crohn’s disease in cattle, called Johne’s disease. MAP has been isolated from some patients with Crohn’s (for example, as reported in this 2004 Lancet paper), and some patients have improved after antibiotic treatment. However, antibiotic treatment can also kill a host of other intestinal bacteria which may also contribute to disease, and some (such as ciprofloxacin) also have anti-inflammatory effects: so their action in alleviating Crohn’s disease may be distinct from bacterial killing. Others, however, have been unable to find MAP in Crohn’s patients, either by culture or DNA techniques. Finally, even if MAP is present, it remains to be confirmed that it is necessary for the development of Crohn’s, or if it is simply a secondary colonizer of damaged intestinal tissue. Animal studies have been done, but again are inconclusive: when fed to young goats, they developed colitis in about 6 months’ time, and a Crohn’s-like disease developed in infected mice, but not other laboratory animals.
Therefore, despite what Borody claims, it’s simply not a straightforward, established cause-effect issue, and it’s not because the medical establishment is simply closed-minded that MAP causation of Crohn’s hasn’t been accepted. Additionally, the acceptance of Helicobacter causation of ulcers, contrary to frequent claims, actually was relatively quick, when one considers the additional experimentation and replication of results that had to be performed by laboratories other than Marshall’s.
However, it’s understandable that some researchers get frustrated when they feel their ideas aren’t being taken seriously by “the establishment.” I, personally, hope Crohn’s is caused by MAP, or another bacterial agent–that points to an easier treatment, and perhaps even a vaccine. But the evidence simply isn’t clear-cut, making it much more difficult to accept such causation, even for those of us who’d welcome it. Just something to consider the next time you see the scientists or doctors being accused of being “closed-minded” by not accepting a claim–perhaps there’s simply more to it than outlined in the story.
Image from http://www.microscopyconsulting.com/Gallery/images/Mycobacterium%20avium.jpg