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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.


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 a 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 the bacterial cell wall and activates NF-kB, which then stimulates the 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 has been associated with Crohn’s and colitis (R, 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

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).

Avoiding common inflammatory food substances such as lectins, gluten, and food additive may help manage IBD. If you suffer from IBD, you may want to consider trying the SelfHacked Lectin Avoidance Diet to see if it might help.

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 the 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].

Gut crypt and butyrate

Gut crypt and butyrate [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):

  • Lactobacillus
  • Bifidobacteria
  • 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 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
  • Eubacterium
  • Peptostreptococcus species
  • Fusobacterium varium
  • Helicobacter species (such as H. pylori) 

Viral Infections

15) Cytomegalovirus Infection May Contribute to UC

Inflammatory cytokines from an inflamed colon, in particular, TNF-alpha, can activate dormant cytomegalovirus and cause it to replicate quickly (R).

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 (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
IL-1beta up arrow up arrow
TNF up arrowup 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

How IBD susceptibility gene products modulate host cells function response to microbial flora. source: doi:10.1038/nature06005

Receptor activation in IBD

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.
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  • 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

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  • phani

    i have crohns, and it amazed me that we could be careful with good diet for eg. a year, then one meal could throw us back into deep sickness.. how could this be? I believe its the balance of good to bad bacteria that changes suddenly, most goods are wiped out for one reason or another, then we are in real strife, cant digest anything, etc… so come in the FMT and crapsules. I tried it myself, i ate poo, yes crap, yes freshly deposited, i put into enteric capsules and downed them, overnight I COULD feel the diffence, suddenly NO BLOATING, NO PAIN, and after a few days of feeling like a normal person, i decided to eat crap – I mean junk food (ha ha), then what happened, 3 days of junk food took me back to bad crohns… there it is… so after 2 weeks of feeling bad, i ate crapsules again, and yes i was good to go again…this all happened in the last 2 months, and i will continue again, but i am sticking to a good diet, to see if my 7cm stricture can heal too. There are good probiotics that can only be found in the gut.

  • Stewart Scott

    Angela, I also had both eczema, later UC, after topical steroids for the eczema, Prednisolone for UC and useless 5ASAs, I’d nearly lost hope of finding relief from eternal cycles of this, until I read about a Professor’s research on Aluminium, testing people for exposure to it by having them drink a silicon rich mineral water, here Volvic, some lucky grad testing the samples. I had nothing to loose so drank 1 litre/day of this, because I’m a coffee addict used the water. It loosened up my stoools so they passed easily, no more burning sensation, passing urine doesn’t hurt anymore, more a pleasure. When water passed through me with a tiny solid, I looked up what is silica. So from health shop bought silica capsules made using bamboo gel, after all you eat bamboo shoots in Chinese meals don’t you? My hair, nails, digestion are good, I used to drink a higher silicate concentration water, but left me oddly thirsty, good idea got start something like Fiji or Acilis, then settle on a water less silicates? The prof calls it a hypersensitivity, but I read eczema might be a type II or III, an Arthos reaction? How are his fingernails or hair? If this helps him, he’ll know if will have any effect within a day or so, did with me. Eczema takes longer to settle, as I’m working mostly towards a healthy gut. Still get Aluminum exposure with water from showering. Maybe this might help?

  • Stewart Scott

    Diana, I had 13 years of hell with UC, they wanted to put me on immunosuppressive drugs after vaccinations, I was not a happy bunny, as luck had it I read how to remove Aluminium salts for my life, I started to drink Volvic water for all drinks, 1 litre/day, that made everything evacuate from intestines, but it was easy done. Then I added a silica capsule made using bamboo gel it stopped water flowing through me (almost), 1 daily. So my UC is ‘in remission’ this way, guts, hair, teeth, all good. Drinking aluminium cleared water kills my guts. Am reading as much as possible about it.


    Hi, I was just diagnosed with a rare IBD called sclerosing mesenteritis. I had a operation that removed my appendix, cecum and the ileum valve, it had grown together. I can’t seem to find much information on this.
    They say it’s a autoimmune condition. I would love to here anything on this condition as to the cause and how to prevent further destruction of my intestines. They want me to take immune suppressents for the rest of my life. I’m 58 yr. female. Thanks, Dee

  • Peter Rutkiewicz

    Really good article. I sympathize with those who suffer from IBD, UC , Crohn and plain colitis, I have lactose intolerance and several food allergies (eggs, soy, nuts, gluten, beef as well as lactose). Its a genetic food sensitivity and some people may have similar symptoms which mimic IBD and is often diagnosed as IBD (or IBS).

    The worst is lactose which will cause a full blown immune system response that is extremely painful and has caused a total of 11 days in the hospital before the cause was finally found. After a decade of full dairy and beef avoidance, I got past the extreme sensitivity and was able to reintroduce lact-aid milk and cultured cheese. Beef was the biggest offender after lactose.

    Beef is something I will only consume once every two to four weeks and 4-5 oz is the limit. The two things that set off food allergies is the volume consumed and the frequency of consumption. I found that the more sensitive the food, the longer the period necessary before consuming again. Keeping the quantity low (i.e. 2 eggs only or 1/4 cup of nuts, not at the same meal), mandatory combining with other foods like vegetables and skipping several days before consuming the sensitive food again are keys to not setting off and worsening food sensitivities. Its also helpful to avoid more than one sensitive item at each meal.

    Olive oil, Canola or coconut oil is a must for me. Corn oil is too inflammatory and soy is an allergy item and asking for trouble (for me, anyways). For a long time, I though I had IBS/IBD but it turns out its food allergies. Usually genetically caused sensitivities will have caused problems as a child (tummy aches, constipation) and other older relatives may have had some sensitivities too so ask around. On the positive side, it made me aware of what I was eating and forced me into a much healthier diet along the lines of Mediterranean and Paleolithic.

    Also, I use a 16 strain probiotic every day which I take with frozen blueberries, strawberries, cheerios and lact-aid milk, or with Pomegranate Juice. Orange juice is too sweet and you should consider eating oranges instead. Same thing for apples vs apple juice.

    Its been over 35 years since being hospitalized and I’ve been free of IBS/IBD symptoms. Discovering the multiple food allergies I had and adjusting my diet accordingly was the key.
    Try to solve the puzzle behind your IBS/IBD as early in your life as you can. You’ll be much healthier and eat a much better diet, Reject everything you know and are accustomed to and relearn what is right for you and what makes nutritional sense. You may have to do the shopping to keep the problematical foods out of your home. Make sure you consume fish at least twice a week. Omega 3 supplementation can help you heal. Good luck.

    1. Angela Sharif

      Hi Peter.
      Was it your hospital stay that identified the foods you were intolerant to? Did you have diarrhea and bleeding before your diet? Did you try to eliminate gluten? My son has been diagnosed with uc and told diet has nothing to do with his uc. I feel differently as when he was a child he gor severe eczema with vows milk and has always been an allergy child. He’s now grown up and has developed uc.
      He’s starting by eliminating gluten and dairy. Fingers crossed.

  • Mike

    Outstanding compilation. I have been trying to pull together data on this since being diagnosed with UC in 1985. It is great having all this in one place with citations, etc. Glad to see you included the work of Ellen S Pierce I am a fan of her theories. Hope to invest in a genetic decode / consult this year.

    1. Nattha Wannissorn

      Thank you!

    2. Peter Rutkiewicz

      UC can also have a food allergy component as a principal cause. Watch out for milk and uncultured cheese, as well as beef. Omega 3 oils can help you heal. Soy oil causes allergy problems for some people. Recommend olive oil and coconut oil. Refined coconut oil is a medium chain triglyceride and will boost your energy level noticeably. Its all I use for eggs now.
      I had UC symptoms too, but it was all genetic allergies which can come on suddenly like a time bomb. It hit me when I was in my thirties.

  • Mito

    Is it possible to control the expression of the genes that correspond to Crohn’s? You stated that in identical twins where one has Crohn’s the other only has a 50% chance of Crohn’s rather than 100%. So specific genes make it more likely to develop Crohn’s, but it is still environmental factors that cause the gene expression and therefore disease. Do we have any idea what they are for Crohn’s?

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