The use of diets such as the autoimmune paleo diet or an elimination/reintroduction protocol is becoming more common for those suffering with autoimmune conditions but also other chronic and neurological health conditions.

But why does some foods seem to cause a problem and others don’t?  Unfortunately there is not one simple reason or one answer, it is individual for each person.

Tolerance is a term used in immunology that describes your bodies’ ability to deal with any particular situation and its reaction to it. Oral tolerance is the bodies’ ability to have an appropriate reaction to foods. For instance, it is not that grains are bad for you; it is that your body’s reaction to grains may be bad for you.

There are number factors at play when considering oral tolerance.

Food sensitivities

For some people some foods do not agree with them, the most common food sensitivities are wheat (gluten), dairy and eggs. Sometimes these sensitivities can remain hidden, as they do not have any obvious immediate consequences when they are consumed. This differs from an IgE mediated food allergy response, which can be immediate and fatal if the susceptible person is exposed to that food.

If you have sensitivity to a particular food you should avoid it, as it will cause inflammation, which then add to the reason as to why you may become reactive to more foods as you age.

If you don’t know that you have sensitivity to a particular food but are suffering with gastrointestinal complaints, or other systemic problems such as fatigue, brain fog or headaches then ruling out a food reaction using appropriate testing will be important.

Loss of digestive function

Good digestive function relies on many factors from the production of adequate stomach acid and digestive enzymes, good liver and gall bladder function, good gut motility and diverse healthy gut microbiome and many others outlined below. 

Stomach Acid

Stomach acid has an extremely important function in the digestion of foods particularly the breakdown of proteins but also the acidity of stomach acid will destroy many pathogens before food proceeds down the digestive tract. 

Proteins are broken down into smaller bits called peptides and these are further broken down into amino acids, which, are then absorbed through the gut and into your blood stream.

Bile acid and other Digestive Enzymes

There are a number of other enzymes that are released into your food as it passes through the gut and these are important for the breakdown of other food types such as fat and carbohydrates. They also help with the absorption of certain nutrients. Bile is released from the gall bladder and other enzymes in the stomach, pancreas, small intestines and even the saliva in your mouth is a digestive enzyme that along with chewing starts the process of breaking down your food.

Gut Motility

In addition to the enzymes and acid used to breakdown food you stomach churns and mixes your food with the enzymes, this churning and mixing continues in your small and large intestines. Your gut walls contracting in a wave facilitate the mixing and movement of food through your gut and this is known as peristalsis.   Gut motility can be affected by many factors but a lack of fibre in the diet; inflammation in the gut lining lack of stomach acid can all affect gut motility.

Hyperactive Dendritic cells

Dendritic cells are immune cells that live in your gut lining. They have long arms, which, wrap around proteins and decide if your immune system should react to the protein. When these are overactive they think that everything they encounter should be reacted to, and are therefore a key part of multiple food sensitivities and loss of oral tolerance.

What causes dendritic cells to become overly reactive? One cause is insufficient breakdown of proteins due to low stomach acid and pancreatic enzymes, another is low Secretory IgA cells. Secretory IgA cells are a type of antibody that are consider the first line of defence in your immune response. Therefore one way to address hyperactive dendritic cells is to improve the breakdown of proteins by increasing stomach acid and digestive enzymes and improve SIgA levels.

One of the biggest factors affecting SIgA levels is cortisol; high levels of cortisol inhibit SIgA function. (Read more about adrenal glands and their hormones here) 

Regulatory T-cells

Regulatory T cells (Treg Cells) decide whether the immune system needs to mount an inflammatory response to a protein the dendritic cells have transported to the lymphatic system. Because the lymphatic system travels throughout body, this inflammatory immune response can cause inflammation anywhere in the body.

Fortunately there are many ways to positive influence Treg cells, to reduce an inflammatory response. 

One of the most effective ways is to make sure that you are getting enough sleep. Adequate sleep is essential to have a properly regulated and functioning immune system.  Another is to do things that you enjoy; laughing and having a good time has been shown to positively impact Treg cells.

Supplementation can also help ensuring you have good levels of Vitamin D3, Omega 3, Glutathione and SCFA’s can be very beneficial to restore oral tolerance.

Leaky Gut

Leaky Gut is a term that is used to refer to intestinal permeability. The cell wall of the intestine is composed of tight junctions, areas where the membranes of adjacent cells join together to form a barrier to the passage of fluid between cells. This is critical for preventing pathogens and other unwanted materials from entering the bloodstream from the gut and causing an inflammatory reaction in the immune system.

Leaky gut is often triggered by gluten and other food sensitivities causing inflammation in the lining of the gut wall. With this inflammation comes a loosening of the tight junction that hold the cells of the gut lining together and it is then possible for inappropriate food proteins and pathogens to enter the blood stream and start an inflammatory immune response throughout the body. It also increases the likelihood or further food sensitivities, inflammation, pain and autoimmune conditions.

The maintenance of tight junctions in the gut relies on a protein called zonulin. Researchers investigating cholera first discovered this protein, when the researchers gave zonulin to animal subjects it created immediate intestinal permeability and this has lead to further research of the leaky gut model.

`For those suffering with celiac disease gluten causes a release of zonulin triggering the tight junctions it also has an affect on the tight junctions that involved in maintaining the blood brain barrier, therefore allowing in appropriate molecules into the brain. Some researchers believe that zonulin release is not specific to those with celiac disease.

Occludin is another messenger protein that has a role to play in leaky gut. When the gut becomes inflamed and breaks down, the immune system will start to make antibodies to occluding and to zonulin. This gives us an opportunity to test and see if someone is suffering from leaky gut by doing a blood test to look for these antibodies. 

Actomyosin antibodies are another indication of intestinal destruction. Actomyosin is a complex of proteins that makes up muscle fibres and contributes to muscular contractions. Antibodies to actomyosin signal a breakdown of the membrane lining the digestive tract and hence leaky gut.

Actomyosin antibodies indicate gut damage is severe enough to break through the cells, not just open the spaces between cells. This type of damage takes longer to repair.

Lipopolysaccharides (LPS)

We also look at antibodies to lipopolysaccharides (LPS), the compound in the membranes of harmful bacteria that trigger inflammation. Immune cells in the mucosal lining do not interact with LPS unless the walls are breached due to leaky gut.

Upon exposure, the immune system produces antibodies to LPS, another marker we can measure to identify leaky gut.

LPS antibodies also signify gut flora dysbiosis, or the overgrowth of harmful bacteria in the digestive tract. When we see LPS antibodies in the bloodstream we know it is causing inflammation throughout the body and may have breached the blood-brain barrier, causing inflammation in the brain.

Antibodies to zonulin, occludin, actomyosin, and LPS are measurable with a blood test, now understood to be the most accurate way to analyse the immune response to intestinal permeability.

Liver function and Oral tolerance

The dendritic cell that seek out proteins in the gut take these to the lymphatic system but also to the liver where a group of immune cells know as Kuppfer cells are responsible for removing or detoxifying the body of bacteria and also food proteins. If your livers detoxification pathways and functions are not working properly this can lead to an inflammatory response. So for some people having a problem with oral tolerance supporting the function of the liver and gall bladder may help to reduce inflammation.

Diversity in Gut Microbiome

This is a key concept in understanding oral tolerance. Our bodies have a symbiotic relationship with bacteria in gut. The key fact to remember is that the diversity, the number of different types of bacteria we have is important. This is particularly important for those who are on restrictive diets where the tendency is to reduce the diversity and types of foods you are eating.

The bacteria in your gut like vegetables and fruit, more specifically the fibre in fruit and vegetables helps to promote gut bacterial diversity and these bacteria then go on to breakdown the fibre and produce SCFA’s (short chain fatty acids). SCFA’s help regulate Treg cells to dampen down inflammation.

Eating a diet that has lots of and a wide variety of different vegetables and fruit in is good for everyone. Just be very careful of the amount of fruit you are eating, it can spike your blood sugar levels.

Blood sugar levels are one of the primary areas of concern for those suffering with health conditions of any kind but especially autoimmune conditions. A spike in blood sugar levels will cause in increase in cortisol and this has a negative effect on you immune system specifically SIgA levels which can further increase problems with inflammation and oral tolerance.

Hormones and Oral tolerance

Hormones are important chemical messengers in the body. We have already mentioned the hormone insulin and its importance in blood sugar management. Also cortisol from the adrenal glands and its role in response to blood sugar spikes, inflammation and the effect it has on the immune system.

The thyroid gland also produces hormones T4 and the active form called T3. T3 is vital of intestinal repair and integrity and therefore important for oral tolerance.

You may also be familiar with testosterone and estrogen – whilst men have more testosterone and women have more estrogen the reality is that men and women have both. They also both have role to play in oral tolerance.

Female Hormone Balance

For women sufficient levels of estrogen is an important factor in regeneration of the gut lining, keeping inflammation in check and brain-gut communication.

The ability to break down and clear estrogens from the body is also important to oral tolerance. Excess estrogen, which is not properly metabolized by the liver, can turn into a more toxic and inflammatory form. 

The most common estrogen problem for women is actually too much estrogen, which can cause symptoms such as bloating, swelling, depression, weight gain, and mood changes.

Excess testosterone in women is actually the most common hormone imbalance for women. It is the number one reason for female hair loss.

Excess testosterone is a result of insulin surges caused by eating too much sugar, too many carbohydrates, or overeating. These insulin surges up regulate an enzyme in the ovaries called 17’20 lyase, which triggers testosterone production. The excess testosterone then promotes insulin resistance in a vicious cycle.

This can play a significant role in loss of oral tolerance.

To lower testosterone, you must support blood sugar stability by eating a diet that does not spike blood sugar and exercising regularly to make insulin receptors more sensitive.

Male Hormone Balance

For men the biggest battle is inflammation.

Leydig cells in the testes make testosterone. Leydig cells are extremely sensitive to and destroyed by inflammation. The testes cannot grow new Leydig cells in an environment of chronic inflammation. Thus testosterone production gradually declines.

Inflammation also increases estrogen in men by up regulating the aromatase enzyme. This not only gives men female characteristics of estrogen (male breasts, crying, hips), but it also further drives down testosterone. Men who use testosterone therapy may see their estrogen levels go up on blood tests due to this mechanism.

Aromatase is in body fat so overweight men may struggle with excess estrogen. When you loose weight estrogen stored in body fat can be released into the bloodstream, worsening symptoms of excess estrogen for a while. This can be modulated with the use of certain natural compounds such as chrysin. 

An aggressive anti-inflammatory diet and lifestyle approach is necessary for men struggling with inflammation-induced hormonal imbalances. 

Diet Lifestyle in Hormone balance

The reality for hormone balance is once you start messing with one you start to mess with them all. Through diet, lifestyle and supplementation you can have a dramatic positive effect on your health by regulating your insulin levels in your blood and the stress response hormone cortisol from the adrenal glands and the modulating effect this can have on all other hormones.

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