Ramon Juste said:
I have read with great interest this paper and I would like to add some evidence supporting the mycobacterial links pointed out in it, as well as comment on some the consequence of lack of a broader, more comparative, perspective on the etiology of these diseases.
A relationship of human intestinal inflammatory disease with the mycobacterial counterpart in ruminants was already pointed out in 1913^6^, even before the index des cription of Crohn?s disease^5^, on the grounds of the pathological similarities between human regional intestinal inflammatory disease and ruminant paratuberculosis. This mycobacterial hypothesis, thus, linked the human form to the ruminant entity first reported in 1895^9^ and generally accepted to be caused by Mycobacterium avium subsp. paratuberculosis (MAP). This microorganism is a bacterial species characterized as slow and fastidious to grow even in specific isolation media. Since its first isolation from human patients by Chiodini et al in 1984^2^, this agent has been repeatedly linked to CD by immunologic^7,14^, epidemoiologic^1,10^, therapeutic^8^ and genetic^4^ approaches. The paper by Jostins et al. more strongly confirms that and brings out a rare disease (mendelian susceptibility to mycobacteria disease-MSMD) that was already postulated as a model for Crohn?s disease 4 years ago on the grounds of the significantly higher levels of circulating IFN-g in the blood of patients than in the blood of controls^13^. In that disease, a deficiency in the IFN-g receptors would disrupt normal transition from innate to adaptive immune response and cause higher levels of IFN-g in blood because of failure to metabolize it through its receptors.
The mycobacterial etiology hypothesis for human inflammatory disease has faced generalized criticism and disinterest among the gastroenterology community and, in our closer Spanish medical community, has prevented testing the apparent effects of certain treatment patterns that in preliminary ?post hoc? analysis seemed to decrease both the blood MAP DNA levels and the disease activity indices^12^. Unfortunately this is coupled with reluctance of the veterinary authorities of most countries to allow the use of the most efficient control measure against paratuberculosis which is vaccination^11,3^. This is a radical approach grounded on a fundamentalist interpretation of interference with bovine tuberculosis tests results (even though bovine TB has become a highly compartmentalized, if increasingly concerning, animal infection and a nearly negligible zoonosis in the countries that have successfully run those schedules). This has caused a silencing of ongoing vaccination practice in cattle, and nearly so in other species except for the successfull recent introduction of vaccination for control of sheep paratuberculosis in Australia.
All this has left the study of relationships of paratuberculosis and Crohn?s disease nearly orphan but for the efforts of a few researchers that cannot collect enough resources to conduct the right research and that generally also miss the deepening of the study of natural disease as a model of intestinal inflammatory disease. On the contrary vast amounts of public funding are devoted to the study of palliative treatments in humans and on paratuberculosis control programs that have repeatedly proven to fail to cure or to eradicate the infection, but that keep patients and farmers chained to long-term expensive programs. The combined result is that cattle production is less efficient and that human population remains exposed and unprotected in front of high environmental levels of the potential cause of such a common and devastating disease. I hope that the current paper will boost research in the trans-species inflammatory hypothesis and thus bring prompt relief to so many intestinal inflammatory patients currently sentenced to a life of symptomatic therapy.
