Thanks helena101 and kiny for the posts. Yes, I think the article I posted early (in post #152) related to a fundamental question: Is IBD like Crohn’s disease caused by an OVER REACTION or DEFICIENCY of the immune system? I know most of the many recent magnificent studies that are published in some of the most prestigious scientific journals, authored by hundreds of elite professionals and achieved by hundreds of millions of funding pointed to uncontrolled infection as the possible cause, with evidences such as: 1) there is a link between CD and NOD2, while NOD2 has been an intracellular receptor recognizing muramyl dipeptide (MDP) existing in certain kinds of bacteria; 2) there is a link between CD and genes related to autophage like ATG16L1, while autophage is related to the destruction and clearance of pathogens inside the cells; 3) there is a striking overlap between susceptibility loci for IBD and mycobacterial infection, as shown by the large scale genome wide association study that involves dozens of thousands of patients and controls; 4) there were increased detection of the adhesive and invasive E. coli (AIDE), Mycobacterium avium paratuberculosis (MAP), enterovirus, etc, in gut tissue of the patients; and 5) as stated by kiny in the previous posts, there is increased infection of bacteria and virus in mutations or deficiency of NOD2 or autophage genes and Crohn’s patients. However, on the hand, we would also have to face another hard fact: suppression of the immune system by anti TNF-alpha antibody and other agents has been the most effective treatment for CD but they increased the risk of infections by bacteria, fungi, and virus, and even of cancer. With these contradiction, I think we may need a more thorough and insightful thinking of the different “facts”to get into the true nature behind these phenomena. In my opinion, the miracle efficacy of the immune suppression agents by far overweighed the other claims, and CD is more likely caused by the over reaction rather the deficiency of the immune system. This notion is in accordance with the finding by Hedl M, Li J, Cho JH, and Abraham C (Chronic stimulation of Nod2 mediates tolerance to bacterial products. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19440-5) that chronic stimulation of the normal NOD2 resulted in tolerance to bacterial products while the Crohn's disease-relevant NOD2 mutation is associated with deficient in this ability of tolerance that leads to escalated inflammation. Thus, as stated in this unified hypothesis discussed here, I believe the weakening of the gut barrier would be the root mechanism of the disease and the increased risk in the mutants of the NOD2 and autophage genes is not due to uncontrolled growth and infection of bacteria or virus but rather the over reaction to the increased infiltration of microbes (live and dead), their debris or metabolites, or antigens from the food, as the result of the deficient in tolerance to the chronic exposure.
