Ulcerative colitis and Crohn’s are two major types of Inflammatory Bowel Diseases (IBDs), which are chronic inflammatory digestive problems of unknown causes. Read this post to learn more about genetics, lifestyle factors, immune system activation, and infections that contribute to IBDs.
Causes and Risks Factors of Crohn’s and Colitis
If someone has Crohn’s, their identical twin with the exact same genetics has 50% chance of developing Crohn’s .If someone has ulcerative colitis, their identical twin has 10% chance of developing colitis .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 .CARD15 mutation results in defective innate immune response to gut bacteria, which can cause dysbiosis in IBD.
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.These mutated genes are mostly expressed in the gut lining, macrophages, and T cells, and cause decreased carnitine transport.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.
4) MDR1 (Multi Drug Resistant 1) is associated with Crohn’s and Colitis
MDR1 transports drugs and foreign substances outside of cells.MDR1 has been associated with Crohn’s and colitis (R, R).MDR1 is associated with treatment-resistant IBD.Mice without MDR1 spontaneously develop colitis.
5) PPAR-gamma is Associated with Crohn’s and Colitis
PPARγ gene has been linked to susceptible of a mouse model of Crohn’s.A rare PPARγ mutation was found to be associated with human Crohn’s disease.PPARγ helps to reduce inflammation by inhibiting NF-kB activity.Ulcerative colitis patients have decreased PPARγ levels.Treatment with a drug that targets PPARγ is effective against ulcerative colitis in a clinical trial .To learn more about PPARγ and how you can improve PPARγ function, read this post.
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.Food additives that can stimulate the immune system and bacterial virulence such as aluminum and iron may also contribute to the development of IBD.
7) Smoking and IBD
Active smoking is a risk factor for Crohn’s disease, but does not affect the outcome or needs for treatment .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.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.
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.Good bacteria metabolites, such as butyrate, may contribute to IBD.Butyrate may prevent stem cells in the gut from growing and repairing the gut after an injury or autoimmune diseases like inflammatory bowel disease(IBD) [R]. Butyrate inhibits the growth of these cells by increasing the Foxo3 gene, which is associated with IBD.
9) Introducing Beneficial Strains Alleviates IBD
Supplementation of probiotic VSL#3 is more effective than placebo at reducing inflammatory bowel disease score in ulcerative colitis patients .In rats, Lactobacillus rhamnosus GG does not prevent colitis, but is superior to Lactobacillus plantarum 299v in preventing recurrent colitis.In another study, L. plantarum 299V helps with immune-mediated colitis in mice.
Protective species include:
specific beneficial E. coli strains
10) Some Strains of E. coli Infection May Contribute to UC
E. coli is a normal part of the gut flora. However, certain strains of E. coli grow rapidly in inflammatory environments produce alpha-hemolysin (a toxin) that causes leaky gut, inflammation, and bleeding characteristic of ulcerative colitis.
11) Mycobacterium avium paratuberculosis (MAP) is Associated with IBD
One of the most studied infections associated with both Crohn’s Disease and Ulcerative Colitis (UC) is called Mycobacterium avium paratuberculosis (MAP).It is thought that besides genetic predisposition, other factors that determine whether MAP manifests as Crohn’s Disease or Ulcerative Colitis is the sex of the individual, his or her age, the route of infection, and the dose.A higher exposure to MAP is associated with Crohn’s while a lower exposure is associated with UC.
12) Salmonella or Campylobacter Infections May Contribute to UC.
Salmonella or Campylobacter infection resulted in an 8 to 10 times increased risk for that person developing UC within 1 year following the infection (R).While the risk for developing UC decreased over time, there was still a heightened risk 10 years post infection (R).One surprisingly high-risk food for both Salmonella and Campylobacterinfections is poultry.In 2011, tests conducted by the National Antimicrobial Resistance Monitoring System (NARMS) found Campylobacter in nearly half (47%) of all the raw chicken they tested at grocery stores .A Salmonella infection may also be derived from raw poultry during food preparation (R). The risk for Salmonella infection is also increased by the presence of live chickens. So, raising your own chickens for meat or eggs does carry risk of infection (R, R2).
13) Clostridium difficile Worsens Outcomes for Those with UC
IBD patients with C. Difficile infection have twice the risk of having a colectomy and 4-6 times the risk of dying (R).
14) Infections of Serpulina,Fusobacterium, Enterobacteriaceae, and/or Gardnerella May Leading to UC
Bacteria that infect the gut, including Serpulina, Fusobacterium, and Enterobacteriaceae can create biofilms on the surface of the gut wall, making it easier for normal gut bacteria to get into the mucosa, where they don’t belong.Fusobacterium varium is significantly higher in the mucosa of patients with ulcerative colitis (84%) than in those with Crohn’s Disease (16%) or other controls (3-13%).A follow up study found that a combination antibiotic therapy against Fusobacterium was effective for patients with Ulcerative Colitis.
Aggressive/detrimental strains include (R):
invasive and toxic E. coli strains
Helicobacter species (such as H. pylori)
15) Cytomegalovirus Infection May Contribute to UC
Inflammatory cytokines from inflamed colon, in particular TNF-alpha, can activate dormant cytomegalovirus and cause it to replicate quickly .Additionally, when immune system is compromised, such as in the case of immune therapy for UC (steroids), Cytomegalovirus can become activated and make the inflammation worse, causing a vicious cycle.