kiny posted several long posts. Frankly, I would like to discuss with people with reasoning, but have no interest to argue with people over arbitrary allegations. You raised a lot of questions. In fact, you can find my answers to most of these questions in my paper or my previous posts.
That's a lot of assumptions, it goes completely against current evidence, and you run into a host of issues by blaming the gut flora and ignoring autophagy:
You should realize that the paper is in fact dealing with the possible relationship among NOD2, autophagy, pathogens and Crohn’s disease with up to date evidences. How can I ignore autophagy?
-you'd have to explain why the first signs of crohn's disease is inflammation of the peyer's patches, peyer's patches sip pathogens with their M cell, not the indingenous luminal bacteria
As stated in
post 168” As we know, the Peyer’s patch has less goblet cells and thinner mucus layer (
http://www.ncbi.nlm.nih.gov/pubmed/7054025 ) and enriched with inflammatory cells, thus would be more vulnerable and sensitive. It would be no surprising that the inflammation started at these sites.” The inflammation would be started once the mucus layer became thinner enough to let just the debris rather the whole bacteria get in, at a stage the surface seems still intact as shown in the area of red ring in your
post #167.
-you're ignoring the thousands of autophagy papers and papers that show autophagy genes like NOD2, ATG16L1 and IRGM are involved in crohn's disease, all related to control of ...shockingly....intracellular bacteria, not the indigenous gut flora
-you're ignoring the fact that people with those mutated autophagy genes actually have a worse disease than those who do not
As shown in the title in the paper as well as the
post 166, I am not ignoring autophagy and NOD2, but provided some new explanation to the massive conflicting evidences.
-you'd have to explain how indigenous luminal bacteria "infiltrate"...they don't, indigenous luminal bacteria don't infiltrate into the submucosa
In fact, the indigenous bacteria in gut lumen can get into the mucosa, into the lymph, into blood and many organs under many situations like the alcoholic and non-alcoholic liver disease, cirrhosis, pancreatitis, shock, burn, etc, even without the apparent damage of the gut like in IBD. Here is a paper:
Berg RD. Bacterial translocation from the gastrointestinal tract. J Med. 1992;23(3-4):217-44.
-you'd have to explain why the immune reaction is transmural, the indigenous flora isn't capable of doing that
Read my
post #118, I have a detailed description there. I have also submitted a manuscript entitled “Why damage is limited to the mucosa in ulcerative colitis while transmural in Crohn’s disease?” to World Journal of Gastrointestinal Pathophysiology and it has been accepted for publication (another journal of conspiracy?). This is an open assess journal and hopefully people can see it soon.
-you'd have to explain why people get fistulas, the indigenous flora isn't capable of doing that
Fistula would be just a further development of the tranmural damage, read my post #118.
-you'd have to explain why the disease is patchy, if it was the indigenous flora causing an immune reaction you'd have inflammation everywhere
The inflammations usually occurred at places where the feces stayed longer (
https://en.wikipedia.org/wiki/Crohn's_disease ), and the inflammation became greatly alleviated after diversion of the luminal content. This would suggest the inflammation are largely caused by the toxic components in gut lumen, rather than an uncontrolled growth of AIEC, MAP, etc, in the macrophages and mucosa.
-you'd have to explain the granuloma, not caused by the indigenous flora
As illustrated in my paper, increased infiltration of bacteria, their debris, or even dietary particles all can cause granuloma.
-you have to explain why classic crohn's disease is regional in the terminal ileum, a pathogen explains this, luminal bacteria do not
How does a pathogen explain this? Because the mucosa at terminal ileum is different from the other sites? Again, it would be the prolonged stay of the feces and high pressure here due to the existence of the ileocecal valve that gave bacteria the chance to penetrate into the mucosa and became flourished there.
-you have to explain why the disease would be in the ileum instead of the colon, the colon has a way higher bacterial load...but there's no inflammation there for many people with crohn's disease
As illustrated in my paper (
Fig. 5), I believe the largely macrophage mediated Crohn’s disease occurred when relative sterile. Otherwise, large amounts of neutrophils will be recruited and manifested as ulcerative colitis. You should realize that Crohn’s Disease just at the colon has become the dominant type in multiple recent studies. For instance, in Stockholm County, Sweden, colonic CD increased from 15% during 1959-1964 to 32% during 1980-1989, and further to 52% during 1990-2001. My paper provided some explanation.
-you're simply ignoring evidence at this point, you're ignoring NOD2 and autophagy
This is the third time of the same accusal. I am tired to reply.
-you're ignoring the fact crohn's disease doesn't look like an immune response against the indigenous flora, it looks like.....intestinal TB, in fact it looks a whole lot like intestinal TB, from the transmural inflammation, to the patchy lesions, to the granuloma, what it doesn't look like at all, is UC
As stated in my
post 118 and the paper to be published, I actually felt CD would be more like tuberculosis and pneumoconiosis in that they mainly involve macrophages and formation of glanulomas.
-you're ignoring the wealth of clinical evidence that AIEC is involved
Back to November last year, in response to your
post #73, I have clearly stated that I do not think AIEC is innocent bystander (see
post #74). In the recent
post #168, I referred you to that post again to clarify my opinion. I am not ignoring it.
-this would be the first disease in history where the body is unable to control the indigenous gut flora
-and the most important one, never has there been an immune response found against the indigenous flora, you actually need to find the immune response against the flora, not just guess that's it's there. You keep wondering if an infection is involved or not, you ignore the fact there is an immune response found against AIEC and MAP, and you're going with a theory that lacks any evidence of an immune response.
As stated in my
post #166, “the gut contains large amounts of LPS (also called endotoxin) that can kill the host thousands of times over, and the long evolution has equipped the body with an innate immune system with defense cells like macrophages being able to launch promptly a vigorous instinct response to low doses of LPS. Thus the inflammation of the gut can be started and continued without any antigen.”
The reason I don't believe in the idea that our own body is somehow attacking our indigenous flora, and that luminal content is somehow infiltrating so deep into tissue that it's causing transmural inflammation and fistulas is because it makes no sense and it's not based on any evidence.
In fact, even under normal condition, the body secretes large amounts (3 - 5 g/day) of antibodies (
Ig A) into the lumen of the gut. This may make no sense to you but is a critical mechanism of front-line defense of the body (
Fagarasan S, Honjo T. Intestinal IgA synthesis: regulation of front-line body
defences. Nat Rev Immunol. 2003 Jan;3(1):63-72). As stated above, the indigenous gut bacteria can be translocated deep into the mucosa and other organs under many situations even with less damage of the gut. There are a lot of evidences.
As you stated, the notion of infection is not new. In fact, from the very beginning, infectious agents had been suspected as the cause and extensively studied. Most people finally gave up this notion due to the failure of the anti-infection treatment. Apparently, a cure would largely depend on finding out the real cause and root mechanism of the disease, which would in turn depends on careful analysis and insightful reasoning of all the evidences.
I have been well ever since, no medicines whatsoever. Thats why i even had the idea. For me it seems kind of obvious that problems in bowel are caused by what you put into it. Nightshades might play a role as well during the leaking from an oversensitive bowel, at least. 
