Intestinal permeability is a hot topic in the health field these days. Consistently there are new journal articles published exploring the correlation between a ‘leaky gut’ and a whole range of different conditions.
This article will help unpack what intestinal permeability actually is. Following articles in this series will cover how it can contribute to different states of disease and lastly alternative approaches to healing and sealing the gut.
Anyone who has studied the human body knows what a fantastic piece of hardware it is. In attempts to maintain homeostasis, a perfect balance, there are hundreds of different mechanisms at work constantly. Some, like breathing, we are very familiar with and aware of. Others, like the protective mucosal layer that forms a barrier between the gut and the rest of our body, are less intuitive but of equal importance to our health and wellbeing.
The gut barrier is a fascinating and important feature of our body. One review helps to outline some key features.
The intestinal barrier
- Covers a surface of approximately 400m2 (that’s more than two tennis courts combined!)
- Takes 40% of our bodies energy to maintain
- Prevents to loss of water and electrolytes
- Prevents the entry of antigens and microorganisms into the body
They are all great and important points but the last one regarding the antigens and the microorganisms is a key takeaway here, especially regarding some negative consequences of an impaired gut barrier aka a ‘leaky gut’.
The same review lists a few more key features including the function of the intestinal barrier to maintain its integrity, perform it’s functions, plus maintain peace with our natural and healthy microflora (dysregulation of this last point seems to be at the root of many inflammatory bowel disease cases)
Anatomy and Physiology of the Gut Barrier
A quick primer on the intestinal barrier is important here. As with many subjects involving health and disease it is more complicated (read sophisticated) than one would assume.
There are two ‘barriers’ at work here.
The first line of defence is the actual mucosal layer that lines our gastrointestinal tract. Predominantly made up from a glycoprotein called mucin it is secreted from, and coats, the epithelial cells underneath (3).
Interestingly the colon has two different layers of mucus. The inner layer appears to be uninhabited by our microflora while the outer layer provides a perfect place for the different bacteria that reside in our gut to live. The small intestine on the other hand has only one layer of mucus and a much lower count in terms of bacterial residents (4).
The layer found under the mucus is made up of a single layer of epithelial cells. These are the cells that secrete the mucus and also provide a range of defence mechanisms ranging from lymphocytes, dendritic cells, paneth cells that secrete antimicrobial peptides and a whole host of others (5).
The Immune System At Work
The gastrointestinal tract is one of the front lines between our body and the rest of the world. It may seem difficult to grasp at first but as a tube that runs through your body what is inside of your digestive lumen hasn’t yet been permitted access into your body.
The intestinal barrier is on constant alert, deciding what is friend and what is foe. This is true to the extent that one paper referred to the intestine as a ‘primary immune system’
‘The intestine represents a primary immune organ with several specialized cell types’
The innate immune system is represented in a number of different ways.
Paneth cells (specialised epithelial cells) secrete a range of different antimicrobial peptides and enzymes – It is thought that one key role the paneth cells play is to protect intestinal stem cells (these cells work to replace intestinal cells every few days). Paneth cells also secrete inflammatory cytokines (messenger molecules) that stimulate the adaptive immune system (6).
It is very interesting to note that generally paneth cells are only found in the small intestine. They can develop in the large intestine in cases of inflammatory bowel disease (Crohn’s disease and ulcerative colitis)(6). What to make of this information is still unclear but as I’ve previously written there seems to be some breakdown in the tolerance of commensal (friendly) bacteria in people suffering from IBD.
Intestinal epithelial cells are another member of the front line defense secreting a range of antimicrobial substances including defensins, cathelicidin and chemokine which attracts dendritic and T-cells (6).
Alongside the innate immune system we have the adaptive immune system, characterised by T and B cell lymphocytes. These cells reside in the mucus associated lymphoid tissue found in the gastrointestinal tract. As part of the adaptive immune system they need to be activated by an antigen (could be a microbe or even food intolerance). T cells can attack the antigen directly and B cells form antibodies, in this case immunoglobulin A (IgA). IgA is a real team player. Studies have shown it has the capability to combat viral and bacterial infections and prevent their adhesion. It also has the ability to neutralise microbial toxins. All in all quite helpful (7).
Control of what passes
The tight junctions are found between each epithelial cell and allow certain substances to pass and bars the entry of others. The other method of entry into the bloodstream is actually through the epithelial cell itself (8). In this manner tight control of what is allowed in is maintained.
What Increases Intestinal Permeability
There are a whole range of factors that affect the permeability of the intestines. Some common offenders from a review published in 2009 include:
Straight from the review
‘Chronic alcohol consumption has been shown to be associated with increased intestinal permeability, inhibition of vitamin and nutrient transport, and a reduction in sodium and water absorption’
Nonsteroidal antiinflammatory drugs are more common than you would think. Pharmaceuticals such as ibuprofen, naproxen, diclofenac, meloxicam, and celecoxib are all common NSAIDs as well as aspirin. A low dose over a short time is advised and longer term or higher dosages come with serious health concerns (10).
Not only are they correlated with gastrointestinal side effects they also play a role in increasing intestinal permeability.
There are a range of gut infections that contribute to intestinal permeability. I would hazard that most do. The pathogens included in the review include
- Vibrio cholerae
- Escherichia coli (the pathogenic strains)
- Clostridium perfringens (a common source of food poisoning)
Glutamine deficiency (8).
A deficiency in the amino acid glutamine has been shown to increase intestinal permeability. The mucosal cells in the gastrointestinal tract utilise glutamine as their energy source and a deficiency in it can lead to atrophied cells.
This is a crucial bit of information and why glutamine is such a popular supplement for helping to reverse intestinal permeability. More on that in an upcoming article.
More On Intestinal Permeability
Now that we have a basic understanding of leaky gut the following two articles in this series will cover disease states that are associated with intestinal permeability as well as some simple approaches to healing leaky gut.
References and Resources
- Intestinal permeability – a new target for disease prevention and therapy
- Inflammatory Bowel Disease – Immune System & The Microbiome
- The intestinal epithelium as guardian of gut barrier integrity
- Role of mucus layers in gut infection and inflammation
- The intestinal epithelium as guardian of gut barrier integrity
- Innate defenses of the intestinal epithelial barrier
- A marvel of mucosal T cells and secretory antibodies for the creation of first lines of defense
- Intestinal barrier function in health and gastrointestinal disease
- Intestinal barrier function: Molecular regulation and disease pathogenesis
- JAMA PATIENT PAGE. Nonsteroidal Anti-inflammatory Drugs.
- The intestinal barrier and its regulation by neuroimmune factors
- Exercise regulation of intestinal tight junction proteins