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Food Ingredients in Bowls

FOOD SENSITIVITIES & 
ORAL TOLERANCE

The mucosal barrier in the gut is exposed to hundreds of different food antigens and millions of bacteria living in contact with it. The majority of oral antigens are seen as harmless or ignored by the immune system.  This is called oral tolerance. 

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If a food antigen (dietary protein) is not broken down properly by the digestive system into amino acids, it may not be tolerated by the immune cells that line the GI tract and a food sensitivity may occur.  Food sensitivities (which produce IgG, IgA & IgM antibody responses) tend to have a delayed response and can cause various reactions such as brain fog, skin issues, fatigue, mucus congestion, slow metabolism, depression or chronic pain.  This is different to immediate allergic reactions (which produce IgE antibody responses) that  cause anaphylaxis reactions.  When antibodies are very high there maybe an abnormal over-reaction or dysfunction in the immune response to food.  T cells can also react to food proteins, especially against gluten proteins in celiac disease.  


Oral tolerance is a complex process performed by the immune system in the gut (see diagram below).  The precise mechanisms are still being researched however, regulatory T cells seem to play an essential role.  Many chronic inflammatory and allergic diseases (e.g. diabetes, Inflammatory Bowel Disease) are strongly influenced by nutritional factors.  An immune reaction to food can certainly fuel the systemic inflammatory response in Autoimmune individuals.  Eliminating these foods altogether or at least ensuring they are fully digested into amino acids to calm the immune response can be helpful in managing autoimmune disease.

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Lab Testing can specify antibodies to sensitive foods (IgG) to identify exactly what to eliminate since the immune system is reacting to this food antigen.

Intestinal immunity and the mechanisms of oral tolerance.

'Intestinal immunity contains both activating and inhibitory immune responses. Tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs) play critical roles in the induction and maintenance of oral tolerance. 


Reference: (Yamashita T, Kasahara K, Emoto T, Matsumoto T, Mizoguchi T, Kitano N, Sasaki N, Hirata K., 2015) 

doi:10.1253/circj.CJ-15-0526

Intestinal Immunity

Food Antigens and Autoimmunity

Modern food production exposes the human body to chemicals and toxins that may abuse the immune system, causing failure in oral tolerance and intestinal permeability to food antigens. This inflammation and gut permeability allows undigested food proteins and commensal bacteria or their toxins to enter the blood stream and be presented to the immune system.  In this situation, TRegs may become dysregulated, thereby disrupting immune homeostasis and exacerbating inflammation.  Once food proteins enter systemic circulation, mast cells trigger inflammatory immune responses and histamine is released.

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As food proteins pass through tight junctions, dendritic cells are the first to sample them.  Quite often dendritic cells can become dysfunctional.  This can be because SIgA in the mucosal barrier drops which protect dendritic cells. SIgA cells are antibodies, immunoglobulins critical for protecting over exposure of dendritic cells to food antigens.  They can be depleted for example with stress or lack of vitamin A. 

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Dendritic cells are activated by retinoic acid (Vitamin A) receptors and are loaded with Vitamin D receptors, so deficiency can lower their function.  Also lack of microbiome diversity can make these dendritic cells over-active.  Once food gets through tight junctions, Antigen Presenting Cells present to T and B cells and inflammation starts.  If TReg cells fail, oral tolerance can be lost.  When we ingest food proteins, these antigens can enter Peyers Patches which can then enter the lymph system and cause systemic inflammation.  They can also enter the portal vein and to the liver.  Over-active Kupffer cells in the liver (macrophages) are caused by constant exposure to antigens.  

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Dietary Antigens associated with Autoimmunity are: Gluten, Dairy, Nightshades, Lectins and specific dietary protein cross reactivity.

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Molecular mimicry-based food immune reactivity

The loss of oral tolerance against food peptide epitopes that share homology with human tissue proteins (such as pig) can result in food immune cross-reactivity and Autoimmunity.  

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Molecular mimicry-based food immune reactivity occurs when a food protein or peptide has a sequence of amino acids that is significantly similar to the structure of a person's own tissue. Normally if the gut barriers are somehow breached and undigested food proteins are able to enter the circulatory system, the body's immune system will mount a response in the form of defensive antibodies against those food proteins. However, if the amino acid peptide sequence of the food particle is sufficiently similar to the structure of a human self-tissue, the immune system will also produce antibodies against the body's own tissue, resulting in autoreactivity and eventually Autoimmune disease.

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During the past decades, significant progress has been made in the search for peptide epitopes in food antigens that share similarities with autoantigens that are involved in Autoimmune diseases. Milk, wheat, plant aquaporins, serpin from legumes, glycine-rich food proteins, glucans, pectins, shrimp tropomyosin, Saccharomyces cerevisiae and pork are some examples of foods that share a significant homology with different human tissue proteins.

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