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. Avoiding lectins in the diet can help ease unwanted inflammation and may calm symptoms, try out our Lectin Avoidance Diet Cookbook to start making great tasting, healthy food now!
- Crohn’s and Ulcerative Colitis Introduction
- Causes and Risks Factors of Crohn’s and Colitis
- Environmental Causes of Leaky Gut
- Interactions between Gut Bacteria and the Gut Immune System
- Pathogenic bacteria and viruses
- Viral Infections
- Probiotic Products that Contain Beneficial Strains
- Health Tools I Wish I Had When I Was Sick
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
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).
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 [R].The gut crypts are structured such that the stem cells at the top are protected from butyrate in the gut. However, in conditions where the villi are sufficiently damaged, the stem cell in the gut may not be protected [R]. Therefore, if you have IBD, butyrate supplementation should be avoided.
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 (R).
In rats, Lactobacillus rhamnosus GG does not prevent colitis, but is superior to Lactobacillus plantarum 299v in preventing recurrent colitis (R).
In another study, L. plantarum 299V helps with immune-mediated colitis in mice (R).
Protective species include (R):
- specific beneficial E. coli strains
- Streptobacillus salivaris
- Saccharomyces boulardii
- Clostridium butyricum
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 (R).
However, it’s possible that E. coli is the consequence of increased inflammation rather than the cause (R).
In fact, the presence and action of E. coli bacteria may actually lower free radical formation by preventing the Fenton reaction, and thereby induce remission (R).
A strain of E. coli, called Nissle 1917, is actually considered the equivalent of mesalazine, generally the drug of choice for treating Ulcerative Colitis (R).
E. coli Nissle 1917 (EcN) is the active ingredient of the microbial drug (pharmaceutical-grade probiotic), Mutaflor® (R).
Pathogenic bacteria and viruses
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) (R).
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 (R).
A higher exposure to MAP is associated with Crohn’s while a lower exposure is associated with UC (R).
This infection is passed from ruminant animals (those that chew their cud) to humans via consumption of MAP-contaminated meat or secretions (milk) (R).
It may also be passed to humans (or between animals) through MAP-contaminated water (R).
Ruminant animals include cattle, bison, sheep, goats, deer, elk, and the like. Therefore, consumption of beef, lamb, dairy (cow, sheep, and goat), venison and other ruminant wild game carries the risk of MAP infection.
One of the arguments for the MAP – IBD connection is a number of instances where not only did a number of family members receive a diagnosis of IBD, but couples or groups of friends living together had co-diagnoses of IBD –indicating an environmental factor in addition to genetic predisposition. In some families, couples, or housemates, some individuals were diagnosed with Crohn’s Disease and others with Ulcerative Colitis (R).
However, a more recent (2016) study found that while MAP was significantly higher in patients with Crohn’s (29%) than controls (0%), no significant difference was found in the prevalence of MAP in patients with UC compared to controls (R).
Another earlier study found no correlation between MAP infection and either Crohn’s or Ulcerative Colitis (R).
It’s also been suggested that while MAP is a fairly common infection, it tends to colonize intestines that are inflamed due to an already active disease process (R).
And so the jury is still out on MAP and IBD.
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 Campylobacter infections 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 (R).
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 (R).
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%) (R).
A follow up study found that a combination antibiotic therapy against Fusobacterium was effective for patients with Ulcerative Colitis (R).
Aggressive/detrimental strains include (R):
- Enterococcus faecalis
- invasive and toxic E. coli strains
- Peptostreptococcus species
- Fusobacterium varium
- 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 (R).
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 (R).
Probiotic Products that Contain Beneficial Strains
Culturelle contains L. rhamnosus GG
Cytokines Associated with Inflammatory Bowel Disease
|Cytokine||Crohn’s disease||Ulcerative colitis|
aRepresentative of a large number of chemokines. Abbreviations: arrow indicates increase; IL, interleukin; N, normal.
|Innate immune response|
Health Tools I Wish I Had When I Was Sick
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
That’s why I decided to create tools that will help others cut down the guesswork:
- Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
- SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
- SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
- SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
- Selfhacked Inflammation course – a video course on inflammation and how to bring it down
- Biohacking insomnia – an ebook on how to get great sleep
- Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
- BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
- SelfHacked VIP – an area where you can ask me (Joe) questions about health topics
The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.
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