Over 80 distinct autoimmune diseases have been identified, with scientists estimating that these autoimmune diseases affect between 4-10% of the global population. Within the United States alone, approximately 50 million people have an autoimmune disease. Unfortunately, the prevalence of autoimmune diseases has been increasing in recent decades. (12, 39) Numerous factors play a role in developing autoimmune diseases, including dietary choices and food sensitivities. Approximately 20% of the population report experiencing food sensitivities or intolerances. In this article, we will discuss possible mechanisms through which food sensitivities play a role in the development of autoimmune diseases and methods available to test for them.

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Defining Autoimmunity and Food Sensitivities

Before diving deeper, let’s define these:

Basics of Autoimmunity 

A normally functioning immune system defends against foreign invaders to prevent disease and infection. In autoimmune diseases, the immune system gets confused and attacks the body's tissues. The tissues or organs affected will vary depending on the type of autoimmune disease an individual is diagnosed with. Autoimmune disorders are generally chronic, so the goal of treatment is to alleviate symptoms and limit or prevent future damage. Some of the most common autoimmune diseases include rheumatoid arthritis (RA), Sjögren's syndrome, systemic lupus erythematosus (SLE), type 1 diabetes, multiple sclerosis (MS), Hashimoto’s thyroiditis, Graves' disease, Crohn’s disease, ulcerative colitis (UC), and celiac disease.

What Are Food Sensitivities? 

There are multiple forms of food reactions, including food intolerances, food allergies, and food sensitivities. One component of our immune system includes immunoglobulins, or antibodies, which are produced by white blood cells. They are used to identify and neutralize foreign objects. In food allergy, immunoglobulin E (IgE) antibodies are produced towards a specific food protein. In food sensitivity, different immunoglobulins, such as IgG and IgA, are produced in response to food proteins. Food intolerances differ from food allergy and food sensitivity in that they are not caused by immune responses. Food intolerances generally occur in the digestive tract and are often the result of an issue in processing or digesting that food. This could be due to an enzyme deficiency or reaction to a food additive or naturally occurring substance like histamine. 

Food sensitivities cause more delayed reactions than food allergies, with symptoms occurring hours to days after consumption. Food sensitivities are not life-threatening, but they can cause discomfort and lead to inflammation. Common symptoms of food sensitivities include:

• Brain fog
• Fatigue
• Gas & bloating
• Irregular bowel movements
• Headaches
• Skin conditions
• Joint pain
• Anxiety and/or depression

The Gut-Immune System Connection

Physical barriers, such as the skin and mucous membranes, serve as first-line defenders of our immune systems. The lining of the gastrointestinal tract is designed to be a semi-permeable barrier. It should allow water and nutrients to be absorbed while preventing partially digested food particles, toxins, and microbes from entering the bloodstream. If this barrier becomes compromised, a condition known as intestinal permeability or leaky gut, these substances can enter the bloodstream, triggering inflammatory responses that can promote autoimmunity. (31) 

70-80% of our immune cells are present in the gut, where they interact with the collection of microorganisms that reside there, known as the microbiome. These different microorganisms influence the development of our immune system. Some commensal microorganisms promote the development of regulatory immune cells that help to control immune responses, while others promote the activity of immune cells involved in inflammation.

How Food Sensitivities Trigger Autoimmune Responses

Food sensitivities can serve as autoimmune triggers through several mechanisms, including intestinal barrier function and molecular mimicry. The intestinal barrier is composed of a lining of epithelial cells that are connected by tight junctions, sealing the spaces between the cells. These tight junctions are dynamic, opening and closing in response to various factors, including dietary proteins to which individuals might be sensitive. When tight junctions are disrupted, microorganisms, toxins, and food proteins enter the bloodstream, activating immune cells and producing inflammatory cytokines involved in autoimmune diseases.

Molecular mimicry occurs when the protein structure of a foreign substance is similar to the protein structure of the host tissue, leading to immune system confusion and an immune response against the host tissue. For example, if gluten-sensitive individuals consume this food protein, the immune system would not only produce antibodies against that food protein but also against glutamic-acid decarboxylase-65 (GAD-65) proteins in the brain, causing a condition called gluten ataxia. Through this mechanism, not only food sensitivities but also chemical and infectious exposures can influence autoimmune responses. (27, 37)

Common Foods Linked to Autoimmune Reactions

Foods commonly associated with autoimmune reactions include wheat, milk, peanuts, soy, egg, and corn. Some food proteins, like gluten found in wheat and some other grains, can directly cause an autoimmune disease. Such is the case in celiac disease, where ingestion of gluten causes some of the body's immune cells, called T-cells, to mount an immune response against it as if it were a foreign invader. The immune system initiates an inflammatory response that damages the small intestine's villi, leading to malabsorption. Gluten consumption can influence the development of autoimmune diseases in less direct means as well. Gliadin, a peptide in gluten, triggers the release of zonulin in the gastrointestinal tract, which can induce intestinal permeability. 

In individuals with gluten sensitivity, gluten consumption can also trigger autoimmune responses through molecular mimicry. Gliadin has a very similar chemical structure to enzymes called transglutaminases. When intestinal permeability is present and gliadin enters the bloodstream, it triggers an immune response not only against gliadin, but also against transglutaminases. Transglutaminases are expressed in very high amounts in thyroid tissue, linking gluten sensitivity to autoimmune thyroid conditions. (1, 25)

Cow’s milk contains casein and β lactoglobulin proteins, which have similar structures to myelin-associated glycoprotein and human protein glycodelin, respectively. Through molecular mimicry, consumption of cow’s milk has been associated with MS and type 1 diabetes. (4, 20) Plant aquaporins, found in corn and soy, have a similar structure to human aquaporin-4, which is located in brain astrocytes. The astrocytes in the brain help to maintain blood-brain barrier integrity. If antibodies are produced against human aquaporin-4 after consuming plant aquaporins, it can induce blood-brain barrier permeability, increasing the risk of neurological autoimmunity. 

Testing for Food Sensitivities and Autoimmunity

If you are interested in testing for autoimmune diseases and food sensitivities, finding a qualified healthcare practitioner who can assist you in ordering the appropriate tests is essential. Moreover, they can make referrals and create a nutrition plan if necessary.

Autoimmune Screening

Anti-nuclear antibodies (ANA) are a type of autoantibody commonly seen in autoimmune diseases. If ANA is positive, an extractable nuclear antigen (ENA) test can be ordered to help identify more precisely which autoimmune disease is present. Other, more specific markers can be ordered if other autoimmune conditions are being considered. Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide (CCP) screen for RA. Thyroid-stimulating hormone (TSH), thyroid-stimulating hormone receptor antibodies (TRAb), thyroid-peroxidase (TPO) antibodies, and thyroglobulin (Tg) antibodies screen for autoimmune thyroid conditions. Sedimentation rate (ESR) and C-reactive protein (CRP) increase in the presence of inflammation. These markers are often elevated in individuals experiencing active autoimmunity. (29)  

Autoantibodies, which can appear years before the onset of autoimmune diseases, can serve as predictors of future disease risk. The Array 5 - Multiple Autoimmune Reactivity Screen detects the predictive antibodies associated with specific autoimmune disorders while also assessing potential tissue damage in various body organs. This is a good test for patients who wish to determine their future risk of developing autoimmune diseases and take preventative measures.

Food Sensitivity Testing

Commonly, testing for food sensitivities includes measuring immunoglobulin levels to specific food antigens. IgG4 antibodies are a subclass of IgG antibodies created to prevent a subsequent inflammatory response to that antigen. C3d is a complement protein that can amplify the immune response to an antigen, increasing inflammation. Cyrex’s Array 10 - Multiple Food Immune Reactivity Screen measures IgG and IgA antibody responses to raw, cooked, and modified foods as well as food enzymes, lectins, and artificial food additives. Many other food sensitivity tests only test against foods in their raw form, which can miss reactions to the food if it is cooked, modified, or combined with other ingredients.

Cell-based food sensitivity testing is another option. Instead of solely focusing on single antibody production to antigens, the ALCAT test measures leukocyte (white blood cell) reactions to 200 foods.

Additional Labs To Test 

The following tests are also helpful for getting a thorough understanding of a patient’s gut health:

Intestinal Permeability Screen

Cyrex’s Array 2 measures antibodies against lipopolysaccharides (LPS), tight junction proteins, and mucosal cell components to identify patients at risk for intestinal permeability.

Managing Autoimmunity Through Dietary Changes

Experts believe that a Western diet contributes to the increased prevalence of autoimmune diseases. This style of diet is characterized by high fat and cholesterol intake, excess sugar and salt intake, and frequent consumption of processed foods. These dietary choices have been linked to many chronic, inflammatory health conditions. Western diets also tend to be deficient in essential micronutrients (vitamins and minerals) that are necessary for all of our cells, including immune cells, to function optimally.

There are specific therapeutic diets that can be utilized in managing autoimmune diseases. A Paleo Diet incorporates foods like lean meats, fruits, and vegetables while eliminating foods like dairy, grains, legumes, processed sugar, and foods. This style of diet is high in phytonutrients that can modulate the immune system and inflammation. An Autoimmune Paleo (AIP) Diet is more restrictive than the traditional Paleo Diet, eliminating all possible food-based inflammatory triggers. Eggs, nuts, seeds, and nightshades are avoided in this diet as well. An elimination diet is the gold standard for diagnosing food sensitivities or intolerances that can sometimes be missed on serum testing. 

All potentially problematic foods or food ingredients/additives should be removed for several weeks. Individual foods are then reintroduced one at a time over a few days to see if any problematic symptoms arise. Any foods that provoke unwanted symptoms are then removed for a more extended period of time before any attempts for reintroduction are made again. The goal of an elimination diet with reintroduction is to temporarily remove foods that promote inflammation, thereby improving the gut and immune health of the patient. This enables patients to gradually transition back to a more nutritionally diverse diet, reducing the likelihood of nutrient deficiencies that can occur when adhering to a strict, long-term elimination diet.

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Summary

In this article, we explored the relationship between autoimmune disease and food sensitivities, delving into underlying mechanisms like intestinal permeability and molecular mimicry. While elimination diets with reintroduction are considered the gold standard for identifying possible food reactions, food sensitivity tests offer an alternative option to tailor dietary recommendations, particularly for patients who prefer more personalized dietary recommendations over highly restrictive elimination diets.