Canada Mark said...
I find it kind of interesting that people (GI's, Researchers etc) have no problem accepting 'dormant' forms of bacteria and the problems that can occur along with the difficulty in treating them in diseases like tuberculosis, etc. - yet when the MAP specific researchers are trying to tell them this is what they think the issue is in Crohn's and maybe IBD in general (dormant forms of MAP) they are labeled 'fringe researchers' or worse...
The term IBD is a misnomer and should not be used in any medical/scientific context because its use is adding to the misunderstanding of these two diseases in my opinion. UC seems more like an autoimmune disease (Disease restricted to colon, whole segment is involved [say, whole sigmoid colon] rather than patchy involvement, and mucosal inflammation) while CD seems more like a persistent infection due to the immune system not being able to clear the infectious agents (transmural inflammation, patchy inflammation [bacterial clusters?], granulomas, whole digestive system [and even skin (1) and theoretically all parts of the body] is involved, antibiotics are effective, genetic predispositions that are related to the immune system's handling of intracellular bacteria (2)(3), defective autophagy, the findings which show high prevalence of intracellular bacteria in Crohn's patients' tissues and blood [compared to UC patients and the general population], Koch's postulates have been met for MAP(4)). The aetiology and pathogenesis of UC and CD are highly distinct from each other. The only things they share are colonic inflammation, some of the treatments used, and colorectal surgery when needed. By the way, immunosuppressants have been used in the past to treat TB, because the Mycobacterium tuberculosis doesn't kill you - the inflammation does.
No one theoretically expects the anti-MAP therapies (be it the antibiotics or vaccines) to positively affect the course of UC in majority of cases.
In theory, there is at least one persistent infection (be it MAP, AIEC or another intracellular pathogen) in Crohn's patients which exploits the host immunodeficiency and the immune activation against it starts the cascade of inflammation that never stops. Basically the immune system attacks; but cannot eradicate the pathogen, and the immune activity/inflammation never stops.
(1): This was first reported in 1976 by Segal et al.
Neutrophil Dysfunction In Crohn's Diseasehttp://www.thelancet.com/journals/lancet/article/piis0140-6736(76)91024-2/abstract
(2): VIEW IMAGE
(3): Crohn's as an immune deficiency: from apparent paradox to evolving paradigm.https://www.ncbi.nlm.nih.gov/pubmed/23256761
Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's diseasehttp://jem.rupress.org/content/206/9/1883.full
Revisiting Crohn's disease as a primary immunodeficiency of macrophageshttp://jem.rupress.org/content/206/9/1839.full
Is Crohn’s disease due to defective immunity?http://gut.bmj.com/content/56/1/2?ijkey=eb8a8854e00027337f2e2a3173ce65be17d31bd0&keytype2=tf_ipsecsha
Defective acute inflammation in Crohn's disease: a clinical investigationhttp://www.thelancet.com/journals/lancet/article/piis0140-6736(06)68265-2/fulltext
Vitamin D, NOD2, autophagy and Crohn’s diseasehttp://www.tandfonline.com/doi/full/10.1586/eci.10.31
Abnormalities in the handling of intracellular bacteria in Crohn's disease: a link between infectious etiology and host genetic susceptibility.https://link.springer.com/article/10.1007%2Fs00005-008-0026-1
Crohn’s disease as an immunodeficiencyhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmc4618314/
Defective innate immunity in inflammatory bowel disease: a Crohn's disease exclusivity?https://insights.ovid.com/pubmed?pmid=21483259
Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease.https://www.ncbi.nlm.nih.gov/pubmed/10877227
Crohn's disease: an immune deficiency state.https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4568313/
Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses.https://www.medscimonit.com/download/index/idart/445257
The immunopathogenesis of Crohn’s disease: a three-stage modelhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmc4529487/
Mycobacteria in Crohn's disease: A persistent hypothesishttps://academic.oup.com/ibdjournal/article-abstract/12/10/1000/4682863?redirectedfrom=fulltext
Mycobacteria in Crohn’s disease: how innate immune deficiency may result in chronic inflammationhttps://www.tandfonline.com/doi/full/10.1586/eci.10.29
Don't remember what study it was, but if you take human MAP antigen, from people with crohn's disease, and infect goats with it, the goat will develop johne's disease.
Another crohnsforum.com member said...
Kiny you may be referring to Koch's postulates fulfilled establishing MAP as a causal agent of Crohn's Disease in Chiodini study:
Van Kruiningen, H.J., Chiodini, R.J., Thayer, W.R., et al. (1986) Experimental disease in infant goats induced by a Mycobacterium isolated from a patient with Crohn’s Disease. A preliminary report. Digestive Diseases and Sciences, 31, 1351-1360.
Dr. Borody also asserts that Koch’s postulates have been met in this interview: https://www.youtube.com/watch?v=crm4pkz6x2m
Koch's postulates: https://en.wikipedia.org/wiki/koch%27s_postulates
Canada Mark said...
Here is the abx testing of RHB-104 against mycobacteria versus the traditional 3 separate antibiotics.
- it's pretty long. The idea being that the three abx combined together and taken all at once seems to be a little more effective than taking the individual doses. Also lower doses are seemingly required.
But they seem to know that they do not get rid of all the bacteria in the samples they take during treatment - "does not fully eradicate the bacteria" as they keep saying. That is why they say it is an 'indefinite' amount of time on the abx. But they seem fairly confident that a reduction in the number of bacteria corresponds with a reduction in symptoms.
Personally I don't like the idea of being on abx 'indefinitely'. But if I were to flare again sometime I think I might try versus biologics. Not sure. Or I would wait until I was uot of options and facing losing my colon perhaps.
A few months ago I researched the antimycobacterials' effects on Mycobacterium avium complex (MAC). Read many studies with different antimycobacterial agents with different combinations and different doses. In the end, I thought to myself that the doctors (they are John Taylor, Borody, Naser I guess) who have created the current anti-MAP antibiotics (Clarithromycin, clofazimine, and rifabutin) plan have done a good job because from my research I realized that this combination has a good synergetic effect (increased effectiveness, decreases the doses needed) and it has a better side effect profile and more effective than others[singular or other combinations]).
Post Edited (xy123) : 12/7/2018 9:06:38 AM (GMT-7)