While the exact<unk>  or<unk> s are unknown, Crohn's<unk>  seems to be due to a combination of environmental factors and genetic predisposition. Crohn's is the first genetically complex<unk>  in which the relationship between genetic risk factors and the immune system is understood in considerable detail. Each individual risk mutation makes a small contribution to the overall risk of Crohn's (approximately 1:200). The genetic data, and direct assessment of immunity, indicates a malfunction in the innate immune system. In this view, the chronic inflammation of Crohn's is<unk> d when the adaptive immune system tries to compensate for a deficient innate immune system. Genetics NOD2 protein model with schematic diagram. Two N-terminal CARD domains (red) connected via helical linker (blue) with central NBD domain (green). At C-terminus LRR domain (cyan) is located. Additionally, some mutations which are associated with certain<unk>  patterns in Crohn's<unk>  are marked in red wire representation. Crohn's has a genetic component. Because of this, siblings of known people with Crohn's are 30 times more likely to develop Crohn's than the general population. The first mutation found to be associated with Crohn's was a frameshift in the NOD2 gene (also known as the CARD15 gene), followed by the discovery of point mutations. Over 30 genes have been associated with Crohn's; a biological function is known for most of them. For example, one association is with mutations in the XBP1 gene, which is involved in the unfolded protein response pathway of the endoplasmic reticulum. The gene variants of NOD2/CARD15 seem to be related with small-bowel involvement. Other well documented genes which increase the risk of developing Crohn's<unk>  are ATG16L1, IL23R, IRGM, and SLC11A1. There is considerable overlap between susceptibility loci for IBD and mycobacterial infections. Genome-wide association studies have shown that Crohn's<unk>  is genetically linked to coeliac<unk> . Crohn's has been linked to the gene LRRK2 with one variant potentially increasing the risk of developing the<unk>  by 70%, while another lowers it by 25%. The gene is responsible for making a protein, which collects and eliminates waste product in cells, and is also associated with Parkinson's<unk> . Immune system There was a prevailing view that Crohn's<unk>  is a primary T cell autoimmune disorder; however, a newer theory hypothesizes that Crohn's results from an impaired innate immunity. The later hypothesis describes impaired cytokine secretion by macrophages, which contributes to impaired innate immunity and leads to a sustained microbial-induced inflammatory response in the colon, where the bacterial load is high. Another theory is that the inflammation of Crohn's was<unk> d by an overactive Th1 and Th17 cytokine response. In 2007, the ATG16L1 gene was implicated in Crohn's<unk> , which may induce autophagy and hinder the body's ability to attack invasive bacteria. Another study theorized that the human immune system traditionally evolved with the presence of parasites inside the body and that the lack thereof due to modern hygiene standards has weakened the immune system. Test subjects were reintroduced to harmless parasites, with positive responses. Microbes It is hypothesized that maintenance of commensal microorganism growth in the GI tract is dysregulated, either as a result or<unk>  of immune dysregulation. There is an apparent connection between Crohn's<unk> , Mycobacterium, other pathogenic bacteria, and genetic markers. A number of studies have suggested a<unk> l role for Mycobacterium avium subspecies paratuberculosis (MAP), which<unk> s a similar<unk> , Johne's<unk> , in cattle. In many individuals, genetic factors predispose individuals to Mycobacterium avium subsp. paratuberculosis infection. This bacterium may produce certain compounds containing mannose, which may protect both itself and various other bacteria from phagocytosis, thereby possibly<unk> ng a variety of secondary infections. NOD2 is a gene involved in Crohn's genetic susceptibility. It is associated with macrophages' diminished ability to phagocytize MAP. This same gene may reduce innate and adaptive immunity in gastrointestinal tissue and impair the ability to resist infection by the MAP bacterium. Macrophages that ingest the MAP bacterium are associated with high production of TNF-α. Other studies have linked specific strains of enteroadherent E. coli to the<unk> . Adherent-invasive Escherichia coli (AIEC), are more common in people with CD, have the ability to make strong biofilms compared to non-AIEC strains correlating with high adhesion and invasion indices of neutrophils and the ability to block autophagy at the autolysosomal step, which allows for intracellular survival of the bacteria and induction of inflammation. Inflammation drives the proliferation of AIEC and dysbiosis in the ileum, irrespective of genotype. AIEC strains replicate extensively inside macrophages inducing the secretion of very large amounts of TNF-α. Mouse studies have suggested some symptoms of Crohn's<unk> ,<unk> ative colitis, and irritable bowel syndrome have the same underlying<unk> . Biopsy samples taken from the colons of all three patient groups were found to produce elevated levels of a serine protease. Experimental introduction of the serine protease into mice has been found to produce widespread pain associated with irritable bowel syndrome, as well as colitis, which is associated with all three<unk> s. Regional and temporal variations in those illnesses follow those associated with infection with the protozoan Blastocystis. The "cold-chain" hypothesis is that psychrotrophic bacteria such as Yersinia and Listeria species contribute to the<unk> . A statistical correlation was found between the advent of the use of refrigeration in the United States and various parts of Europe and the rise of the<unk> . There is also a tentative association between Candida colonization and Crohn's<unk> . Still, these relationships between specific pathogens and Crohn's<unk>  remain unclear. Environmental factors The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein, and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids. Those who consume vegetable proteins appear to have a lower incidence of Crohn's<unk> . Consumption of fish protein has no association. Smoking increases the risk of the return of active<unk>  (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohn's. Although stress is sometimes claimed to exacerbate Crohn's<unk> , there is no concrete evidence to support such claim. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in patients with Crohn's. The use of doxycycline has also been associated with increased risk of developing inflammatory bowel<unk> s. In one large retrospective study, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing Crohn's<unk> .
medical cause of Peptic ulcer disease
symptoms of Helicobacter pylori
medical cause of Gastritis
symptom of Helicobacter pylori
symptom of Ulcerative colitis
symptom of Small intestine cancer
symptom of Stomach cancer
complications of Helicobacter pylori