The Crohnie

An interesting new piece of research about the genetics of Crohn’s Disease Diabetes and other diseases.
http://www.nature.com/nature/journal/v447/n7145/pdf/nature05911.pdf

I note that one of the gene patterns associated with Crohn’s relates to “autophagy”, an innate immunity mechanism which the body uses to defend itself against intracellular bacterial pathogens.

http://en.wikipedia.org/wiki/Autophagy

“”"
The study has also confirmed the importance of a process known as autophagy in the development of Crohn’s disease. Autophagy, or “self eating”, is responsible for clearing unwanted material, such as bacteria, from within cells. The may be key to the interaction of gut bacteria in health and in inflammatory bowel disease and could have clinical significance in the future.
“”"

http://www.medicalnewstoday.com/medicalnews.php?newsid=73420

“”"
One of the newly identified genes, called ATG16L1, has been thought to be required for autophagy, a process that leads to programmed cell death and is involved in the process of inflammation. When the research team used RNA interference to suppress the gene’s activity in bacterially infected cells, decreased molecular action associated with autophagy confirmed that the process depends on ATG16L1 activity.
“”"

http://www.sciencedaily.com/releases/2007/04/070415160159.htm

Autophagy is one of the most important defenses against the class of intracellular bacterial pathogens known as mycobacteria. One of the most studied organisms in relation to autophagy is mycobacterium tuberculosis

Autophagy in Immune Defense Against Mycobacterium tuberculosis
http://www.landesbioscience.com/journals/autophagy/article/2830

Mycobacterium avium subspecies paratuberculosis (MAP) is another intracellular obligate pathogen with which autophagy would be a key defense mechanism.

So it is no surprise to me that recent results indicate a defective autophagy process in Crohn’s Disease; this lends further weight to the theory that Mycobacerium paratuberculosis is a cause of Crohn’s Disease.

On the action of 5-amino-salicylic acid and sulfapyridine on M. avium including subspecies paratuberculosis.
Greenstein RJ, Su L, Shahidi A, Brown ST.
PLoS ONE. 2007 Jun 13;2(6):e516

http://www.ncbi.nlm.nih.gov/pubmed/17565369

Full Text

Abstract

BACKGROUND: Introduced in 1942, sulfasalazine (a conjugate of 5-aminosalicylic acid (5-ASA) and sulfapyridine) is the most prescribed medication used to treat “inflammatory” bowel disease (IBD.) Although controversial, there are increasingly compelling data that Mycobacterium avium subspecies paratuberculosis (MAP) may be an etiological agent in some or all of IBD. We have shown that two other agents used in the therapy of IBD (methotrexate and 6-MP) profoundly inhibit MAP growth. We concluded that their most plausible mechanism of action is as antiMAP antibiotics. We herein hypothesize that the mechanism of action of 5-ASA and/or sulfapyridine may also simply be to inhibit MAP growth. METHODOLOGY: The effect on MAP growth kinetics by sulfasalazine and its components were evaluated in bacterial culture of two strains each of MAP and M. avium, using a radiometric ((14)CO(2) BACTEC(R)) detection system that quantifies mycobacterial growth as arbitrary “growth index units” (GI). Efficacy data are presented as “percent decrease in cumulative GI” (%-DeltacGI). PRINCIPAL FINDINGS: There are disparate responses to 5-ASA and sulfapyridine in the two subspecies. Against MAP, 5-ASA is inhibitory in a dose-dependent manner (MAP ATCC 19698 46%-DeltacGI at 64 microg/ml), whereas sulfapyridine has virtually no effect. In contrast, against M. avium ATCC 25291, 5-ASA has no effect, whereas sulfapyridine (88%-DeltacGI at 4 microg/ml) is as effective as methotrexate, our positive control (88%-DeltacGI at 4 microg/ml). CONCLUSIONS: 5-ASA inhibits MAP growth in culture. We posit that, unknowingly, the medical profession has been treating MAP infections since sulfasalazine’s introduction in 1942. These observations may explain, in part, why MAP has not previously been identified as a human pathogen. We conclude that henceforth in clinical trials evaluating antiMAP agents in IBD, if considered ethical, the use of 5-ASA (as well as methotrexate and 6-MP) should be excluded from control groups.