I just read a really great paper ("Mycobacterium avium subspecies paratuberculosis and its relationship with Crohn’s disease") that summarized recent literature on the role of Mycobacterium avium paratuberculosis (MAP) in Crohn's Disease. I've had several previous posts regarding MAP's potential role in Crohn's and IBD, but this paper was much more comprehensive and cited studies I had not heard of.It's really worth reading the whole thing if you're looking for background on this topic. Here were the topics covered:
- Introduction
- MAP - description and background on the MAP bacterium
- Detection of Map in Crohn's Disease - intro of detection techniques
- MAP Culture - different methods of culturing MAP and results of studies related to Crohn's
- Detection of Insertion Sequence IS900 - methods of detecting the IS900 gene sequence (which is unique to MAP)
- Serologic Studies of MAP - looking for antibodies in the blood of Crohn's patients
- MAP and Genetic Susceptibility to Crohn's Disease - interaction between genetic susceptibility (via the NOD2/CARD15 Crohn's gene mutations) and MAP (e.g. overgrowth, etc.)
- Anti-Mycobacterial Antibiotics for Crohn's Disease - review of studies that tried (unsuccessfully) to cause long-term remission of Crohn's through use of antibiotics. MAP is very resilient and the interaction between antibiotics and immunosuppressive agents (which may also impact MAP function) leave room for doubt in the studies.
- Epidemiologic Evidence for MAP as a Cause of CD - lots of epidemiologic evidence for why MAP is likely not the cause of Crohn's, but some support of it being a cause.
- Conclusion (full excerpt below)
For reference, I'm including an excerpt of the conclusion of the paper:
MAP is the causative agent of Johne’s disease. It seems likely that chronic infection with MAP does occasionally occur in humans. MAP is widely present in our food chain and the DNA of this organism can be recovered from the intestine of CD patients. Studies have shown that a high percentage of subjects with CD are infected with MAP, though whether the association of this bacterium and CD is causal or coincidental is not known. Epidemiologists have gathered enough information to indicate an association between MAP and CD. Nonetheless, the role of MAP in CD etiology is not known, and may be determined from consistent results of studies using improved methods of isolation and detection of MAP bacilli and/or MAP-elicited immune responses in the host.
It's a great theory, but one major question remains: if MAP is the cause of CD, why does the disease not worsen with the application of immunomodulators and TNF inhibitors? Infection with Mycobacterium tuberculosis is a strict contraindication for the use of TNF inhibitors, as it will almost certainly cause the disorder to go out of control.
ReplyDeleteDefinitely. The paper comments on that specifically (in the Antibiotics section). It's a good argument against MAP being a sole cause. On a related note, though, they also comment on some research that might point to why there might be some "interactive effect" between traditional immunosuppressive drugs and antibiotics. But agreed on the TNF inhibitors.
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