Inflammatory Bowel Disease: The Immune System & The Microbiome connection

inflammatory bowel disease heal your gut byron herbalist naturopath gut health

Both ulcerative colitis and Crohn’s disease are inflammatory, recurrent, bowel diseases. Ulcerative colitis is characterised by abdominal pain, bloody diarrhea and fluctuating inflammation of the mucosal lining found in the colon and the rectum (1, 2).

Similar in many ways, Crohn’s disease is characterised by ulcerations found predominantly in the ileocolonic (90%) although the hallmark ulcerations of Crohn’s can occur anywhere throughout the gastrointestinal tract, from the mouth to the anus (3).

While there are many studies exploring the disease the exact pathogenesis is still unknown. The thinking around both disease states to date involves the genetic makeup of an individual as well as environmental factors that trigger an overactive, inflammatory immune response in the gastrointestinal tract (4). Much of the science is pointing towards the gut microbiome as one of the key environmental factors that triggers the immune response and studies have cited food antigens as another factor (5).

One paper nicely outlines the thinking to date

“Overwhelming evidence has accumulated supporting the hypothesis that IBD is the result of a genetically determined, overly aggressive immune response towards ubiquitous luminal antigens, especially commensal bacteria and their products” (6).

In layman’s terms this translates to concept that the immune system is mounting an attack on it’s own resident microflora.

As the immune stimulus for IBD is still not completely clear, common treatments include immune suppression/modulating and anti inflammatory drugs. With the root cause of the immune response undealt with many IBD patients (20-30%) suffer relapses or fail to respond outright (7).

 

Environmental Factors in IBD

An interesting paper looked at the different theories on the origin or pathogenesis of IBD in an individual. It outlined a relatively small amount of science pointing towards IBD being an autoimmune condition, characterised by B-cell autoantibodies and T-cell activation against epithelial cells. In 1967 serum antibodies targeting the epithelium in the colon were found in ulcerative colitis patients. Interestingly the antibodies detected were cross-reactive with  Escherichia coli, a resident of the gastrointestinal microbiota.

The paper continues by outlining the immune-mediated aspects of Crohn’s disease and ulcerative colitis by outlining the relationship between our gut microbiota, which outnumbers human cells by a factor of 10 times!

The coexistence of the immune system and a bacterial population of such a large size is complicated to say the least.

When bacteria are first introduced it stimulates an immune response, characterised by inflammation. Once the immune system recognises non-pathogenic (beneficial and commensal organisms) the immune response ceases and coexistence between host and bacteria takes place.

One way of thinking about this interaction is that the immune system recognises the microflora of our bowels as self and doesn’t mount an attack.

Now what happens if that balance is disrupted?

This is one of the leading theories on IBD proposed by the same paper with three different scenarios leading up to the imbalance between the immune system and the microbiome.

  1. The microflora has had a significant change in composition
  2. The immune system’s response to the microflora is altered
  3. The balancing mechanism between self and resident bacteria is absent

Now What? Take Away Points on Inflammatory Bowel Disease Insights

What do we do with this information?

That is the million dollar question. Seeing as the consequence of IBD is a proinflammatory state my impulse is to start with the diet. Whether IBD is characterised more so by autoimmunity or by an external immune response a focus on consuming an anti inflammatory diet, free from popular food allergens is a good start.

The elimination diet is a good place to start. Food sensitivity testings can be expensive and unreliable but may help paint a picture if necessary.

Dysbiosis & Inflammatory Bowel Disease

Another place to look would be the resident microbiota. There have been many studies looking into the possible dysbiotic microflora including

  • One study found significantly lower levels of Roseburia hominis and Faecalibacterium prausnitzii, two beneficial microbes, in a selection of ulcerative colitis patients compared to controls. F prausnitzii in particular has been shown to be anti inflammatory. The absence of these microbes could be significant in the inflammatory response seen in IBD patients –
    A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in the screened patients with ulcerative colitis
  • Another paper reviewing dysbiosis and the implications in disease cited several studies looking into the microbiota of IBD patients. One cited study found an overabundance from the Bacteroides phylum. While this phylum is well represented in a healthy human microbiome an overabundant imbalance has been correlated with poor outcomes.
  • The same review looked to possible pathobionts (organisms known to cause pathology) and found a correlation between expansions of the family Enterobacteriaceae and colitis in animal studies. The Enterobacteriaceae is home to species including Escherichia coli, Shigella and Klebsiella spp. Seeing as most of the findings come from animal studies there isn’t enough information to draw proper conclusions but it is interesting. To lend weight to the idea expansion of Enterobacteriaceae members are found in the tissues and stool samples from people with ulcerative colitis and Crohn’s disease.

Keeping Our Findings In Perspective

It is important to keep the conclusions of the numerous studies on IBD and the microbiome in perspective. In an attempt to summarise the findings an article published in 2004 in Gut reminded the readers of a number of important things

  • Most of the studies rely on techniques used to analyse and describe the microbiota that miss much of the big picture. In recent years advances in testing including PCR assays have improved the approach.
  • Even if we do have the tools to see the complete human microbiome there is much that we don’t recognise and understand.
  • There is a distinct difference between the mucosal flora and the faecal flora. While this may seem like a trivial matter in the case of inflammatory bowel disease it may be incredibly important as outlined above.

The same paper concludes with something that I would like to pick up on in a later article

“Emerging therapies for IBD include probiotics and prebiotics. There is good animal data to support the beneficial effects of many commensal bacteria on immune function and mucosal integrity. However, there remain very few well designed randomised clinical trials of probiotics in IBD.”

Thankfully this was published in 2004. Since that time there have been a range of studies, including the randomised control trials, looking into the effects of probiotics in IBD.

A future article will explore the possible benefits of probiotics in IBD and review the scientific findings.

Do you suffer from gut issues like IBD? Share your thoughts on what has helped in the comments below

References and Resources

  1. Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL # 3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study
  2. Ulcerative colitis
  3. Diagnostic Modalities in Crohn’s Disease
  4. Understanding Crohn Disease and Ulcerative Colitis
  5. Breakthrough Lactobacillus rhamnosus GG bacteremia associated with probiotic use in an adult patient with severe active ulcerative colitis: case report and review of the literature
  6. Rationale for probiotic treatment strategies in inflammatory bowel disease
  7. The Probiotic Preparation, VSL#3 Induces Remission in Patients With Mild-to-Moderately Active Ulcerative Colitis
  8. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?
  9. 30 Day Elimination Challenge
  10. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis
  11. Microreview Defining dysbiosis and its influence on host immunity and disease
  12. Dysbiosis in inflammatory bowel disease
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