As we have learned, we are totally dependent on the semi-permeability of our gut and body barrier linings. Simply put, these control what gets through into our blood stream and what doesn’t.
There are several factors that can cause the gut to become more permeable than it should be (some examples are in the diagram we saw earlier from renowned immunologist Prof Vodjani).
Those include deficiency of nutrients such as glutamine, attack by pathogens such as bacteria (as in gastroenteritis, gram-negative bacteria like E Coli/Helicobacter pylori, and small bowel bacteria overgrowth), yeasts and parasites (like candida) and viruses, stress, drugs and meds (such as ibuprofen and antibiotics), alcohol excess, constipation (and generally slow transit of food through the digestive system) and an imbalanced immune system.
The problem is that if someone continues to eat the intolerance food, the adaptive immune system is on call all the time and this is really draining for the body. No wonder we all feel tired and are susceptible to infections as the body is distracted all the time. If a person continues to do the stuff that encourages a leaky gut and more zonulin production specifically, as in gluten ingestion, then the problem is not only going to continue but that’s what causes the so-called ‘allergic march’ where we become sensitive to more and more things.
Gluten and The Zonulin Issue
The main one: quick summary. Gluten is known to upregulate the production of a substance called zonulin, which controls the permeability of the gut wall. Too much gluten = too much zonulin = barrier breakdown. In fact, there is much excitement at the possibility of using a zonulin-based drug to deliberately induce leaky gut to enhance the delivery of a drug. The mind boggles; what else could be let through?
Loss of Gut Protection
Secretory IgA (SIgA) is also a common factor. SIgA is the main immunoglobulin in mucus secretions. A sticky lining of mucus is our first-line defence against gastro-intestinal pathogens like bacteria, food proteins, parasites, fungi, toxins and viruses, both by acting as a type of physical barrier, a trap for opportunistic bacterial nasties and as a reservoir of the all-important SIgA.
Simply put, the SIgA antibodies prevent micro-organisms, food proteins and carcinogens from binding to the surface of absorptive cells. Effectively, they attach themselves to invading nasties, trap them in mucus and stop them from going anywhere. The antibodies also ‘tag’ foods as acceptable to the body and this suggests why low SIgA levels can be a key to developing and progressive food allergy and intolerance. Leaky gut is also related since, if levels are low, repair of mucosal tissues can be compromised. It is simple to test for SIgA levels to see if this is a factor in your case. You can do it via stool or saliva.
Pathogens – Yeasts, Bacteria, Viruses, Parasites
It may be that our digestive systems aren’t that healthy and organisms like candida yeast, having been allowed through by a faulty digestive system or lack of SIgA protection have made our guts leaky, thus allowing prohibited food protein molecules through.
Candida yeast is present in all of us, but given a lot of sugar in the diet, events to upset the beneficial bacteria levels (eg antibiotics) and stress, it can perform a sort of metabolic switch. If this happens, it can produce protein digesting enzymes, which enable it to cling to the intestinal walls, increase greatly in number and then no diet is going to get rid of it.
This will cause gut irritation, contributing to the leaky gut, as well as inflammation and the release of toxic compounds into the body environment. A simple stool test looking for the enzyme ‘secreted aspartic protease,’ ie. a SAPS positive candida where it has made the switch, is the best way to test.
Candida blood tests look for an antibody, which could have developed years ago and may reflect a past infection, so, in my opinion, are not as reliable.
Other parasites, bacteria and viruses can also play havoc with the gut environment. In fact, viral or gastrointestinal infection is thought by many to be the initial trigger for gluten sensitivity and a loss of oral tolerance in allergy to develop.
An overgrowth of gram negative bacteria (such as E. Coli or Helicobacter Pylori) often termed ‘Small Intestine Bacterial Overgrowth’ leads to an increase in endotoxins, which increase barrier permeability and puts more pressure on the liver.
Any healing programme needs to identify and treat any issues because the gut is unlikely to heal whilst under constant attack.
Poor Liver Function
Imagine that something like a food antigen, toxic metabolite from a bacteria or whatever has gained entry into the abdominal circulation via a leaky gut. Where does it go first? To the liver. And what happens if the liver is not up to the job of filtering and destroying the invader? It goes on to wreak its havoc. So, it stands to reason that liver health must be optimal if we want to dampen down any allergen issues.
Raised liver enzymes are often seen in people with coeliac disease, who are also found to have leaky gut. In fact, raised liver enzymes can sometimes be the sole indicator of a gluten sensitivity. In most cases, they will normalise within 12 months off gluten. It may be that the gluten causes inflammation and/or autoimmune attack on the liver in the same way as it can do with any organ.
Glutathione is a key anti-oxidant for the liver to protect against this type of attack and low levels have been commonly found in people with leaky gut syndrome. Interestingly, glutamine, the main barrier energy source, is crucial for replenishing glutathione levels and is included in your Barrier protocol.
Loss Of Immune Tolerance
One immune-based theory is that there may be too many T helper cells in the immune system and not enough suppressor cells – a sign of an imbalanced immune system needing support.
It is thought that changes in several areas has led to a change in the way our immune system operates: environmental (more toxic), nutritional (change of diet to higher grain and dairy, intensive farming techniques, loss of nutrients in soil), helminthic (loss of worms we evolved with) and bacterial (change in the overall balance of good and bad bacterial strains).
We are thought now to have an immune system that is more likely to produce TH1, TH2 and TH17 type responses against previously benign substances, thus making them allergens, promoting inflammation without sufficient bodily means to calm it down.
In fact, some research is now suggesting that if we put back the correct types of bacteria and worms into the system, it can have a beneficial effect on allergen immunity because the body almost has something else to concentrate on. Such so-called ‘stimulation’ of the host immune response has also been shown to effect the release of an enzyme called IDO [idoleamine-2,3 dioxgenase] which is thought to regulate T cell tolerance so a therapy worth keeping our eye on for the future.
Put simply, when we eat foods, we must digest them. Normally, the bowel and liver are responsible for filtering out food molecules and toxins. Often, for various reasons, we do not produce enough stomach acid or pancreatic enzymes for this to work efficiently.
If a food is not broken down enough, undigested foods like glutens can enter the intestines and cause harm. They can irritate the delicate bowel lining and cause inflammation which eventually weakens the bowel wall, it becomes more permeable and allows foreign particles that it normally keeps out through into the blood stream.
They can then provide substrates for bacteria and organisms to live on upsetting the delicate balance between good and bad organisms in the gut and causing toxic damage. They can also get caught in pockets and stuck to the walls if the person is constipated and putrefy, again damaging the bowel wall and producing lots of toxic waste. By this time, the bowel is in a sorry state.
Some people simply do not have the enzymes to break food down. This can be general in that their production of pancreatic enzymes has become inefficient. Or, you can have a specific enzyme issue such as lactase deficiency (lactose intolerance), DAO deficiency (histamine intolerance) and GLUT-5 deficiency (fructose intolerance).
People who are genetically gluten sensitive and go on to form coeliac disease will have a terrible time absorbing as the villi in the gut (which provides the large surface area for absorption of nutrients) is effectively flattened. A gluten free diet is necessary to allow the villi to regrow.
Other absorption issues can be caused because the person simply doesn’t have enough energy for body mechanisms to work properly. This could be because their thyroid is underactive, their adrenals are exhausted, they are insulin-resistant or they simply don’t have enough of the right nutrients including magnesium and potassium for the energy metabolic pump Na/K-ATP-ase to keep up with demand.
Certain foods, including chilli (a gut irritant) and food families like lectins can cause havoc. Too much sugar slows the food transit time down leading to more gut toxins irritating the gut wall and entering the blood. Sulphur-sensitive people can get too much hydrogen sulphide in the body, a gas thought to damage the barrier lining and thin the protective mucus layer.
Other people have problems with ‘natural’ food substances including amines (often in migraines, think cheese, chocolate), lactose (an enzyme deficiency, see below), MSG, nitrates/nitrites, histamines, fructose (an inability to absorb sugars properly), nightshades, salicylates and caffeine. Non-food problems can come from additives and agrochemicals, to name a couple.
Although we can pinpoint a lot of the physiological causes of illness, we would be daft to ignore the effect the mind and spirit can have. The so-called gut-brain link is well-known; we have the biggest number of nerves in our gut and what we think can certainly affect what we feel physically. Just think of ‘butterflies’ in your stomach when anxious, for example, or the increase in bowel movement frequency when we’re worried.
A whole area of medicine, called PNI [psycho-neuro-immunology], is now dedicated to this. Any programme to correct immune or gut issues has to involve some sort of stress management like meditation, visualisation, massage, hypnosis or something that triggers the autonomic nervous response and calms us down.
From a physical perspective, we know that stress is associated with reduced levels of friendly bacteria, the production of the so-important SIgA and the thickness of the protective mucus lining. Stress also leads to an increase in some stress hormones, the catecholamines like norepinephrine, which are thought to increase the presence of pathogens in the gut.
Some studies have shown that food-sensitive people often have lowered hypothalamic-pituitary-adrenal axis function. In other words, the communication between the major hormone organs is not as effective as it should be. This is known to increase the risk of inflammation and sensitivity. You often see this in people whose symptom reactivity is affected by stress, hormone patterns and the circadian rhythm (your body clock).
As you can see, this is a complex issue. Once you have become hyper-permeable or, if you like, your barriers are broken, allergens from anything can gain entry into the body where they shouldn’t be. This is most likely to be via the gut first with food, obviously, but once skin, lung and blood-brain barriers are also hyper-permeable, you become sensitive to toiletries (via the skin), pollens and chemicals (inhalation) and onward. Eventually, inflammation and immune processes, especially auto-immunity, can occur anywhere in any organ or tissue, which explains why the symptoms are so diverse. Coeliac disease is just one auto-immune reaction which happens to have affected the villi, but it is certainly not the only one.
What To Do About It
So, what does it all mean for treatment purposes? If we are to have any chance of stopping the process, we have to be pretty on the ball at getting that barrier function repaired. We have to stop doing the stuff that causes hyper-permeability and increase the amount of work we do to repair it. Consider the barrier tests and the barrier treatment plan.