Leaky Gut & Autoimmune Diseases

Leaky gut is a condition that for a long time was dismissed as non existent, yet now it is accepted and its development and aetiology is well understood, and leaky gut symptoms are commonly reported to clinicians. With this increased understanding of the condition, it has opened up possible links in the development of autoimmune conditions. Leaky gut really just refers to increased permeability of the gut wall. The gut is semi permeable, or should we say selectively permeable. Of course it has the ability to let things pass through it, but these are things that are of benefit to us. It also has the ability to keep things out. Therefore selectively permeable. 

The gut as a barrier

The epithelial lining of the gut, along with different secretions produced by it and microbial life forms a barrier that separates us from the external environment. It is a selective and secure border between the inner workings of the body and the outside world. This lining must be able to allow the good stuff ie nutrients in, and keep the bad potentially pathogenic influences at bay. As such it is a very tightly organised, multilayered barrier defines system. If the integrity of this barrier is compromised in any way, then we open ourselves up to a whole host of problems that can arise locally, systemically, or both. 

The first layer of defence that we have within the gut lining is the diverse bacterial colony. Our gut bacteria, gut flora, microbiome. They go by many names but the microbiome is a diverse and highly active bacterial colony that lives in the gut. They regulate many aspects of localised gut function, synthesise certain vitamins, and create a physical barrier against pathogens that can also instigate biochemical defences in the form of bacteriocins - chemicals that will selectively destroy harmful bacteria whilst conserving our friendly gut bacteria. 

The next defensive layer is the mucous layer. This is a layer of mucous that sits between the gut bacteria, and the enterocytes and other cells that physically make up the wall of the gut. This layer exists to contain the bacteria that make up the gut bacteria colony within their specific environment - the gut lumen. Whilst they are dubbed “friendly”, this term may be a little simplistic. What we really should say is that this bacteria is beneficial when residing in its intended environment. If however it got the opportunity to penetrate other tissues, then infection would ensue. As long as it stays where it is, then it plays a vital role in our health.

 The other layer of defence worth talking about in the context of leaky gut and autoimmune conditions are the tight junctions. These are bands of connective tissue that bind the enterocytes tightly together. The enterocytes are the cells that side by side make up the endothelium. As you can see in the diagram, there of course is a space between each of them. This is held tightly closed by the presence of tight junctions. This stops large molecules or pathogens from entering our systemic circulation and causing trouble. 

Barrier breakdown

What we see above is a basic overview of the barrier system present within the gut. When it is all working well our body isn't presented with too many challenges very often. However, things can go wrong and this barrier system can break down. If this occurs, the gut can become more permeable, which allows the entry of exterior antigens from inside the gut to enter the host - us. This is when we have what is termed a leaky gut. So how does this happen? How does a leaky gut develop? Well, there are many potential causes of a breakdown here, but the two biggest ones are dietary induced, and stress induced. 

Dietary breakdown of gut barrier function

It stands to reason that the food that we eat, or as we will see, don’t eat, will make an impact upon the local environment of the gut. It is the one environmental factor that is consistent. Something that enters the gut 3 times a day. The composition of the diet directly influences the whole picture. 

Studies are ongoing in relation to vitamin D and tight junction function. There are also ongoing studies as to how certain dietary components such as gliadins within gluten can affect susceptible individuals and degrade the tight junctions. 

However, one of the most widely understood links so far, and one that can be easily rectified is the level of fibre consumed. We need dietary fibre, in abundance for many reasons. It can swell up and stimulate peristalsis in the gut which keeps everything moving along nicely to keep us regular. It can help to lower cholesterol by binding to cholesterol in the gut and carrying it away. But most relevant to this discussion, many of the polysaccharides (large complex sugars) that make up dietary fibre, are actually a food source for our gut bacteria. The gut microbiome will actually ferment these polysaccharides and as they ferment them, they reproduce in number, and secrete by products such as the short chain fatty acids butyrate and propionate that have many benefits. 

The above is all well and good providing we have a wide array of fibre coming in via our daily diet - ie lots of fruit and vegetables. A whole foods diet. Unfortunately many of us have an incredibly low fibre intake. Living on white bread, white rice, meat and cheese (I love meat and cheese so not demonising them, but they don’t deliver fibre). When we consistently have a low fibre diet, the gut bacteria can start to get pretty hungry. If this happens, they then turn to the only available source of polysaccharides, one that is incredibly close by - the mucous layer. Mucous is made up of polysaccharides so if their needs are not met our gut bacteria will in time begin to turn on the mucous layer as a food source. They will start to consume it and wear it away. When this happens, areas of the mucous layer wear away and expose the endothelial cells underneath. When these are exposed, many more environmental factors can directly interact with them. These can be gut bacteria, pathogens, particles of food at different stages of digestion etc. When these influences interact with the enterocytes, the tight junctions that bind them together can become degraded. When this happens, the gap between enterocytes can become larger or may yield to pathogenic interference and antigens can pass through and enter our body. This is when the trouble arises.

Other factors influencing barrier dysfunction

Other factors can also disrupt barrier function, usually by altering the gut bacteria quality and what the microbiome are actually doing. These are stressors, two in particular. The first being chronic alcohol consumption which affects both the quality and quantity of gut bacteria and also can effect the mucosal lining too. 

The second is infection. Many pathogens that can cause infection even when a healthy barrier is present (ie food Bourne pathogens etc) can cause rapid breakdown of the mucosal layer. 

Barrier dysfunction and autoimmune diseases

Now we know how leaky gut arises, let's explore its relationship to autoimmune diseases. If something can penetrate the dysfunctional barrier, whether this is a bacteria, a pathogen, a partially digested food item or the like, there is a very high chance that an immunological response will occur to a degree that can be problematic. It may manifest as a transient infection. It may of course go on to create an immunological event that causes single or repeated damage to specific tissues and structures. The immune system will respond to foreign bodies getting past these defences, it is the luck of the draw whether this will manifest as a disease state.

There are several disease states that have been associated with barrier dysfunction, the first is the one that should be the most obvious - inflammatory bowel disease. There is still debate as to whether this is a true autoimmune condition, or whether it is injury that arises as a result of inflammatory damage from localised immunological reactions. Whichever, the fact remains that mucosal layer degradation can lead to an immunological response within the area local to the compromised barrier. This can lead to blistering and inflamed sores in the bowel. 

The next of the big autoimmune diseases is type 1 diabetes. This is the diabetes that we often associate as being childhood onset, the type that is insulin dependant throughout the life cycle. This is very hotly debated but some clinical studies such as that described by Secondulfo et al (2004), and Damci et al (2003)  have shown a very strong correlation between degradation of the mucosal layer and the onset or exacerbation of Type 1 diabetes. It is believed that a protein called zonulin is at play here, and is something often associated with the instigation of leaky gut, especially when gluten is the trigger. 

The next autoimmune condition where leaky gut has a potential link is Systemic Lupus Erythematosus. This is a condition that consists of sever and persistent inflammation in multiple organs causing considerable system wide damage. A substance called LPS or bacterial Lipo PolySaccharide has been identified as a component in the causation of lupus. When it penetrates the intestine and translocates into tissues where it can trigger aggressive responses. 

So how could we turn this around?

It is possible to turn known cases of leaky gut around and this is something I have done in clinical practice using my 3 R protocol. The three R’s - Repair, Reinoculate, Reinforce. The first stage is repair. 

Stage 1 - Repair. The gut, due to the fact it is exposed to so many stimuli on an ongoing basis, is susceptible to damage and as such is geared towards constant repair and restoration which comes in the form of cell proliferation and replication, given the right environment. The amino acid glutamine is a very important energy source for the enterocytes especially to fuel these types of repair mechanisms. Taking 1000mg of glutamine twice daily for a full month helps to repair the damage to the gut lining that has caused the leaky gut to develop.

Stage 2 - Reinoculate. Once we have created a better internal environment within the gut for our gut bacteria to flourish in, we need to reintroduce it as best we can. Remember that there can be anywhere between 500 to 1000 different strains of bacteria living within the gut at any one time, and only a few we have access to in a supplement from. But, the reinoculation stage means getting gut bacteria back in by means of using a broad spectrum probiotic. There are many types of probiotics on the market but you want to find one with as many different strains of bacteria in it as possible. Continuing to take glutamine in this second month, begin taking the broad spectrum probiotic alongside to reintroduce bacteria to strengthen the microbiome. 

Stage 3 - Reinforce.  At month three we need to reinforce the first two stages. At this point we add a broad PREbiotic supplement. A prebiotic is something that, as discussed at the start of this article, is a food stuff for our gut bacteria, and a healthy supply of probiotics means a healthy microbiome. A supplement containing FOS (fructo Oligosaccharide) and Inulin should be taken for the third month, alongside the glutamine and the broad spectrum probiotics still. 

After this three month protocol, the supplements can be dropped but a diet that is very plant centric is a must. The broader intake of fibrous plants, whole grains, legumes etc we have, the more probiotics we take in and the better our gut flora develops. 

References

Damci T, Nuhoglu I, Devranoglu G, Osar Z, Demir M, Ilkova H. Increased intestinal permeability as a cause of fluctuating postprandial blood glucose levels in type 1 diabetic patients. Eur J Clin Invest (2003) 33(5):397–401.

Secondulfo M, Iafusco D, Carratu R, deMagistris L, Sapone A, Generoso M, et al. Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients. Dig Liver Dis (2004) 36(1):35–45.