Now that we have covered what intestinal permeability or ‘leaky gut’ actually is we can now move onto some possible health conditions associated with the condition.
As previously covered the intestinal barrier forms a front line defence against anything we consume. There are numerous mechanisms that work tirelessly to monitor what is allowed passage from the gastrointestinal tract into the body proper.
With impaired intestinal permeability there is a breakdown in this finely tuned mechanism and things that normally are not allowed into the body slip through the cracks.
Connecting Leaky Gut to Disease States
In the paper Leaky Gut and Autoimmune Diseases Alessio Fasano, a lead researcher into celiac disease, proposed the connection between autoimmune diseases and leaky gut.
He listed three different elements that must be present for an autoimmune condition to arise
‘The genetic susceptibility of the host immune system to recognize, and potentially misinterpret, an environmental antigen presented within the gastrointestinal tract’ – Alessio Fasasno
This has been a widely held belief for some time now. A genetic predisposition to certain autoimmune diseases increases one’s risk of getting said disease. It is incredibly important to understand the key word here – risk. Having a specific set of genes that might predispose you to getting a disease does not mean that it is a foregone conclusion that you will get the disease.
Other factors need to be present.
With a genetic susceptibility to one or more ‘autoimmune’ triggers the person must then be exposed to the trigger or antigen.
Celiac disease is an excellent example of this point. We know that the gluten protein is the trigger that sets off the immune system, producing auto-antibodies directed at the self. Removing the trigger, or environmental stimulus gluten, halts the progression of celiac disease.
In the 2011 paper, Fassano lists intestinal permeability as the third factor that must be present for the development of an autoimmune disease to progress.
This is a new concept that is gaining traction as researchers make the connection between autoimmune conditions and raised intestinal permeability.
The increased intestinal permeability appears to involve a human protein called zonulin. Zonulin release, triggered by certain bacteria, has the ability to induce leaky gut by increasing the permeability of the tight junctions found in the gut. Increased tight junction permeability then allows molecules past the gut barrier and into circulation (3).
Intestinal permeability, caused by increased zonulin, has been implicated in a number of autoimmune diseases including coeliac disease.
Type 1 diabetes is also characterised by high levels of zonulin. In one paper 42% of type 1 diabetic patients had abnormally high levels of zonulin compared to controls. To take that a step further 70% of pre-type 1 diabetics showed increased zonulin levels (4).
Leaky Gut & Other Disease States
Fasano lists a range of other disease states that are associated with elevated zonulin and increased intestinal permeability
- Multiple sclerosis
- Inflammatory bowel disease (Crohn’s disease and Ulcerative colitis)
- Ankylosing Spondylitis
To me this seems like quite a breakthrough in understanding the development of autoimmune diseases. Looking deeper into the literature it appears that a number of other disease states, not just autoimmunity, are correlated with leaky gut.
- Food allergies (8).
- Irritable bowel syndrome (IBS) (9).
- Ménière disease (10).
- Parkinson’s disease (11).
It is worth mentioning the old chicken or the egg concept here. As with many things we are still fumbling around in the dark with much of the scientific findings connecting intestinal permeability to different disease states. Does leaky gut cause or contribute to the disease progression or is it a result from having the disease? The answer to this key question is still being explored and may be different depending on the disease.
That said I think it is important to understand the connection between leaky gut and many different autoimmune and non-autoimmune mediated diseases.
The next article in this series will cover strategies to healing and sealing leaky gut.
References and Resources
- Leaky Gut – What is Intestinal Permeability
- Leaky Gut and Autoimmune Diseases
- Zonulin, regulation of tight junctions, and autoimmune diseases
- Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease
- Multiple Sclerosis – A Functional View
- Inflammatory Bowel Disease – Immune System & The Microbiome
- Klebsiella – Ankylosing Spondylitis, Reactive Arthritis & Infections
- Intestinal Epithelial Barrier Dysfunction in Food Hypersensitivity
- Intestinal permeability and irritable bowel syndrome
- Intestinal permeability and Ménière’s disease
- Intestinal permeability and orocaecal transit time in elderly patients with Parkinson’s disease