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12 IBD (Ulcerative Colitis and Crohn’s) Contributing Factors

Written by Nattha Wannissorn, PhD | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Nattha Wannissorn, PhD | Last updated:
IBD

Ulcerative colitis and Crohn’s are two major types of Inflammatory Bowel Diseases (IBD), 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 IBD.

What is IBD (Ulcerative Colitis and Crohn’s)?

Crohn’s disease and ulcerative colitis (UC) are two of the most frequently diagnosed subtypes of inflammatory bowel disease (IBD).

IBD is a group of 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 [1].

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). It involves ulcerations of all cell layers of the gut lining [1].

Crohn’s disease mainly involves Th1 and Th17 overactivation [2].

Characteristics of Ulcerative Colitis

Ulcerative colitis typically affects the colon and rectum. It involves the inflammation of the mucosal layer (innermost cell layer) of the gut [1].

It is mainly a Th2 dominant condition, although in some cases it is not clear [2].

Potential IBD Contributing Factors

None of the below factors are established causes of IBD. According to preliminary research, they may play a role in this complex disease, but the evidence is inconclusive. If you recognize one or more of these factors in your case, it doesn’t mean you have IBD. If you’re experiencing digestive issues, work with your doctor to get adequate diagnosis and treatment.

Genetics

It’s important to note that just because certain genotypes are associated with a condition or irregular lab marker, it doesn’t necessarily mean that everyone with that genotype will actually develop the condition. Many different factors, including other genetic and environmental factors, can influence the risk of IBD.

If someone has Crohn’s (CD), their identical twin with the exact same genetics has a 50% chance of developing Crohn’s [3].

If someone has ulcerative colitis (UC), their identical twin has a 10% chance of developing colitis [3].

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 (CD)

CARD15 binds to the bacterial cell wall and activates NF-kB, which then stimulates the production of proinflammatory signals [4].

CARD15 mutation results in a defective innate immune response to gut bacteria, which can cause dysbiosis in IBD [5].

2) OCTN1 and OCTN2 (CD)

Two genetic mutations that in OCTN1 and OCTN2, SLC22A4 and SLC22A5, respectively, have been associated with Crohn’s disease [6].

These mutated genes are mostly expressed in the gut lining, macrophages, and T cells, and cause decreased carnitine transport [6].

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 (CD)

DLG5 helps maintain gut lining integrity.

A mutation (G113A) of DLG5 is associated with a CARD15 mutation in Crohn’s disease [7].

4) MDR1 (Multi-Drug Resistant 1) (CD & UC)

MDR1 transports drugs and foreign substances outside of cells [8].

MDR1 has been associated with Crohn’s and colitis [8].

MDR1 is associated with treatment-resistant IBD [9].

Mice without MDR1 spontaneously develop colitis [10].

5) PPAR-Gamma (CD & UC)

PPARγ gene has been linked to susceptible to a mouse model of Crohn’s [11].

A rare PPARγ mutation was found to be associated with human Crohn’s disease [11].

PPARγ helps to reduce inflammation by inhibiting NF-kB activity.

Ulcerative colitis patients have decreased PPARγ levels [12].

Treatment with a drug that targets PPARγ was effective against ulcerative colitis in one clinical trial [13].

To learn more about PPARγ, read this post.

Environmental Factors

6) Smoking

Active smoking is a risk factor for Crohn’s disease but does not affect the outcome or needs for treatment [14].

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 a worsened outcome for ulcerative colitis [14].

7) NSAIDs

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 [15].

Mice lacking IL-10 and taking an NSAID developed colitis within 2 weeks [16].

8) Diet

According to preliminary research, lectins and gluten may contribute to gut inflammation in sensitive individuals [17, 18, 19].

Food additives and contaminants that can stimulate the immune system and bacterial virulence, such as aluminum and iron, may also contribute to the development of IBD [20].

Avoiding common inflammatory food substances such as lectins, gluten, and food additives may help prevent gut inflammation. Elimination diets such as the Lectin Avoidance Diet can help identify and remove such food irritants.

Bacterial Infections

9) Mycobacterium avium paratuberculosis (MAP)

One of the most studied infections associated with both Crohn’s disease and ulcerative colitis (UC) is called Mycobacterium avium paratuberculosis (MAP) [21].

Besides genetic predisposition, other factors that determine whether MAP manifests as CD or UC include the sex of the individual, age, the route of infection, and the dose. Higher exposure to MAP is associated with Crohn’s while a lower exposure is associated with UC [21].

This infection is passed from ruminant animals (those that chew their cud) to humans via consumption of MAP-contaminated meat or secretions (milk). Ruminant animals include cattle, bison, sheep, goats, deer, elk, and the like [22].

It may also be passed to humans (or between animals) through MAP-contaminated water [21].

One of the arguments for the MAP – IBD connection is a number of instances where family members, couples, and groups of friends living together had co-diagnosed IBD, indicating an environmental factor in addition to genetic predisposition [21].

10) Salmonella or Campylobacter Infections

In one trial, Salmonella or Campylobacter infection resulted in 8 to 10 times increased risk of UC within 1 year following the infection [23].

While the risk for developing UC decreased over time, there was still a heightened risk 10 years post infection [23].

One surprisingly high-risk food for both Salmonella and Campylobacter infections is poultry.

In 2011, tests conducted by the National Antimicrobial Resistance Monitoring System (NARMS) found Campylobacter in nearly half (47%) of the raw chicken samples they tested at grocery stores [24].

A Salmonella infection may also be derived from raw poultry during food preparation. The risk of Salmonella infection is also increased by the presence of live chickens [25, 26, 27].

11) Other

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 [28].

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%) [28].

Aggressive/detrimental strains include [29]:

  • Enterococcus faecalis
  • C. Difficile
  • invasive and toxic E. coli strains
  • Eubacterium
  • Peptostreptococcus species
  • Fusobacterium varium
  • Helicobacter species (such as H. pylori)

Viral Infections

12) Cytomegalovirus

Inflammatory cytokines from an inflamed colon, in particular, TNF-alpha, can activate dormant cytomegalovirus and cause it to replicate quickly [30].

Additionally, when the 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 [30].

Technicals

Cytokines Associated with Inflammatory Bowel Disease

(source: http://www.nature.com/nrgastro/journal/v3/n7/fig_tab/ncpgasthep0528_T2.html)

Cytokine Crohn’s disease Ulcerative colitis
aRepresentative of a large number of chemokines. Abbreviations: the arrow indicates increase; IL, interleukin; N, normal.
Innate immune response
IL-1 beta up arrow up arrow
TNF up arrow up arrow
IL-6 up arrow up arrow
IL-8a up arrow up arrow
IL-12 up arrow N
IL-18 up arrow up arrow
IL-23 up arrow N
IL-27 up arrow N
T-cell response
IFN-gamma up arrow N
IL-5 N up arrow
IL-13 N up arrow
IL-17 up arrow N
IL-21 up arrow N

nature06005-f3-2

http://www.nature.com/nrgastro/journal/v3/n7/full/ncpgasthep0528.html

About the Author

Nattha Wannissorn

Nattha Wannissorn

PhD
Nattha received her Ph.D. in Molecular Genetics from the University of Toronto and her undergraduate degree in Molecular and Computational Biology from the University of Pennsylvania.
Aside from having spent 15 years in biomedical research and health sciences, Nattha is also a registered holistic nutritionist, a certified personal trainer, has a precision nutrition level 1 certification, and is a certified functional diagnostic nutrition practitioner. As a holistic practitioner with a strong science background, Nattha is an advocate of science literacy in health topics and self-experimentation.

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