Crohn’s and Ulcerative Colitis Introduction
Crohn’s and Ulcerative Colitis are two of the most frequently diagnosed subtypes of inflammatory bowel diseases (IBD).
IBDs are chronic inflammatory diseases characterized by inflammation and sores in the gut lining, which can result in diarrhea, abdominal pain, fatigue, fever, rectal bleeding, nutritional deficiencies, and weight loss (R).
Both innate and acquired immunity are activated in IBD, although Crohn’s and colitis follow different patterns of T-cell activation.
Characteristics of Crohn’s Disease
Crohn’s may affect any portion of the gastrointestinal tract, but mostly in the ileum (lower portion of the small intestine) (R).
Crohn’s disease mainly involves Th1 and Th17 overactivation (R).
Crohn’s disease involves ulcerations of all cell layers of the gut lining (R).
Characteristics of Ulcerative Colitis
Ulcerative colitis typically affects the colon and rectum (R).
It is mainly a Th2 dominant condition, although in some cases it is not clear (R).
Ulcerative colitis involves the inflammation of the mucosal layer (innermost cell layer) of the gut (R).
Causes and Risks Factors of Crohn’s and Colitis
Genetics
If someone has Crohn’s, their identical twin with the exact same genetics has 50% chance of developing Crohn’s (R).
If someone has ulcerative colitis, their identical twin has 10% chance of developing colitis (R).
Genetics, therefore, contributes to the development of IBD, but is not the sole cause.
Genes that have been associated with Crohn’s and colitis include:
1) CARD15 is Associated with Crohn’s Disease
CARD15 binds to bacterial cell wall, and activates NF-kB, which then stimulates production of proinflammatory signals (R).
CARD15 mutation results in defective innate immune response to gut bacteria, which can cause dysbiosis in IBD (R).
2) OCTN1 and OCTN2 are Associated with Crohn’s Disease
Two genetic mutations that in OCTN1 and OCTN2, SLC22A4 and SLC22A5, respectively, have been associated with Crohn’s disease (R).
These mutated genes are mostly expressed in the gut lining, macrophages, and T cells, and cause decreased carnitine transport (R).
However, there is still no direct evidence other than genetic data that demonstrate that these two genes are directly involved in the development of IBD.
3) DLG5 is Associated with Crohn’s Disease and Ulcerative Colitis
DLG5 helps maintain gut lining integrity.
A mutation (G113A) of DLG5 is associated with CARD15 mutation in Crohn’s disease (R).
4) MDR1 (Multi Drug Resistant 1) is associated with Crohn’s and Colitis
MDR1 transports drugs and foreign substances outside of cells (R).
MDR1 is associated with treatment-resistant IBD (R).
Mice without MDR1 spontaneously develop colitis (R).
5) PPAR-gamma is Associated with Crohn’s and Colitis
PPARγ gene has been linked to susceptible of a mouse model of Crohn’s (R).
A rare PPARγ mutation was found to be associated with human Crohn’s disease (R).
PPARγ helps to reduce inflammation by inhibiting NF-kB activity.
Ulcerative colitis patients have decreased PPARγ levels (R).
Treatment with a drug that targets PPARγ is effective against ulcerative colitis in a clinical trial (R).
To learn more about PPARγ and how you can improve PPARγ function, read this post.
Environmental Causes of Leaky Gut
5) NSAIDs can Cause Leaky Gut and IBD
NSAID painkillers can temporarily create inflammation and leaky gut, leading to activation of the gut immune system by components of normal gut bacteria (that wouldn’t otherwise cause a problem).
Leaky gut caused by NSAIDs can stimulate T-cell-mediated intestinal inflammation and cause IBD in genetically susceptible humans (R).
Mice lacking IL-10 taking an NSAID develop colitis within 2 weeks (R).
6) Diet can Contribute to IBD
Dietary components that cause cause leaky gut, such as lectins and gluten can contribute to the development of IBD (R).
Food additives that can stimulate the immune system and bacterial virulence such as aluminum and iron may also contribute to the development of IBD (R).
7) Smoking and IBD
Active smoking is a risk factor for Crohn’s disease, but does not affect the outcome or needs for treatment (R).
Interestingly, smoking is associated with better outcomes for ulcerative colitis, as indicated by reduced needs for treatments and surgery. In addition, quitting smoking is associated with worsened outcome for ulcerative colitis (R).
Interactions between Gut Bacteria and the Gut Immune System
In IBD, gut bacteria interact with receptors on the surface of gut lining and gut immune cells (TLR and NOD2 receptors) thus activating NF-kB signaling and causing inflammation (R).
8) Normal Gut Bacteria Causes Inflammation Only in Crohn’s and Colitis
In mice lacking IL-10, native (commensal) bacterial species like Enteroccocus faecalis and E. coli increases gut inflammation. These two bacterial strains don’t cause increased inflammation in mice that have normal IL-10 (R).
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