Autoimmunity, Gut Health and Diet: Connect the Dots

According to the National Institute of Health (NIH), autoimmune disease is recognized in approximately 24 million individuals in the U.S., consisting of more than 80 various disorders that contribute to the top 10 causes of death in female children and women of all age groups.¹ Autoimmune disorders are theorized to develop from an interaction among genetic susceptibility factors, epigenetic effects, environmental triggers and dietary triggers.²

Autoimmunity: Exploring Mechanisms and Pathology

One of the most commonly identified dietary triggers is the gastrointestinal pathology celiac disease (CD). Clinicians acknowledge that with CD, intake of gluten proteins result in significant enteropathy characterized by inflammation of the proximal small intestine. Gluten proteins, present in wheat, barley, and rye, are rich in glutamine and proline residues.

The diagnosis of CD includes tissue transglutaminase (tTG) or transglutaminase 2 (TG2) auto-antibodies, resulting in a gluten-specific CD4+Th1 T-cell activation and an immune response that causes an upregulation of zonulin.³ Medical researcher and clinician Dr. Alessio Fasano discovered that zonulin, an inflammatory protein, assists in regulating barrier function in the GI tract by altering the intercellular tight junctions, leading to impairment of intestinal permeability and absorption.⁴

Most recently, a multitude of research has shown that patients diagnosed with non-celiac autoimmune disease have responded favorably to a diet free of gluten or other proteins within the gluten family.⁵ The unique component about any autoimmune disorder is the immune system can erroneously target any other organ or system of the body, rendering it to malfunction. Some examples of popular autoimmune pathology consist of: alopecia, urticaria, scleroderma, vitiligo, multiple sclerosis, type 1 diabetes, Graves' disease, ulcerative colitis, aplastic anemia, pernicious anemia, psoriatic arthritis, rheumatoid arthritis, and sarcoidosis.⁴

Autoimmune disorders typically fall into two categories: systemic and local. Systemic autoimmune diseases are associated with auto-antibodies which are not tissue specific, so a broad range of organs and systems can be affected. Localized autoimmune diseases are associated with organ-specific conditions that affect a single organ or tissue.⁵

As previously stated, the mechanisms of autoimmunity are complex and multifaceted, arising from a combination of the inheritance of susceptibility genes and environmental triggers. For purposes of this article, let's focus on the gastrointestinal microbiota dysbiosis (also referred to as dysbacteriosis) hypothesis and defective bidirectional gut-brain communication as possible causal relationship of the development of autoimmunity.

Ever-increasing consumption of a modern Westernized diet high in sugar, processed grains, low-quality seed oils and fatty grain fed meats has a detrimental impact on the microflora of the gastrointestinal tract, and has been shown to induce intestinal dysbiosis and impair gut integrity.

GI Function and Dysfunction

The gastrointestinal tract functions to digest and absorb nutrients from food, but these same foods provide exposure to dietary antigens, microorganisms, parasites and bacterial products that can have damaging effects on mucosal and host health beyond the gastrointestinal tract.⁶ The gastrointestinal barrier is the physical and functional separation between the environment and the host's interior, and therefore plays a crucial role in one's health and disease by regulating (allowing and preventing) what substances enter the system.⁷

The GI tract also has the largest collection of immune cells, consisting of 70 percent of all lymphoid tissue in the body (Peyer's patches, mesenteric lymph nodes, activated T cells, mast cells, macrophages, and plasma cells) that can provide effective immune responses when needed.

Dysfunction of the GI tract will have detrimental effects on its several functions, as well as considerable impact on the rest of the body. Therefore, more importance has been given to the role of the gastrointestinal microbiota including nutrition, energy metabolism, host defense, and immune system development.⁸

In pathological conditions, the permeability of the epithelial lining may be compromised, allowing the passage of toxins, antigens, and bacteria in the lumen to enter the bloodstream, creating a "leaky gut."⁹ Common contributing factors that increase intestinal permeability (leaky gut) are ethanol consumption, a highly processed diet, nonsteroidal anti-inflammatory drug (NSAID) use, prescription corticosteroids, Candida overgrowth, chemotherapy, radiation therapy, impaired digestion (low stomach acid), bacterial, viral, yeast and protozoan infections, and food that frequently irritate the GI lining such as dietary gluten, dairy, and corn.

In genetically susceptible individuals, a leaky gut may allow environmental factors to enter the body and trigger the initiation and development of nonspecific activation of the immune system's inflammatory pathways, leading to autoimmune disease.¹⁰

Molecular Mimicry and Autoimmunity

Molecular mimicry occurs when one molecule mimics another molecule in the way it behaves in the body. In regards to the chronic autoimmune diseases, a foreign antigen unexpectedly shares a similar structure with self-antigens, which can lead to inflammation and destruction of particular tissues and organs.¹¹ This is what may occur in patients who do not meet the criteria for celiac disease (CD) or wheat allergy, but do report several intestinal and extra-intestinal symptoms after consuming gluten-containing foods.

This pathology is termed non-celiac gluten sensitivity (NCGS) and wheat sensitivity (WS). Although the pathophysiology of NCGS / WS remains largely undetermined, as there are no biomarkers for NCGS or WS, positive anti-gliadin antibodies (primarily IgG and IgA) have been found in 25 percent and 50 percent of the NCGS and WS cases, respectively.¹²

Most importantly, NCGS and WS are further characterized by resolution of symptoms with a GF diet, and relapse of symptoms with gluten/wheat exposure. The clinical picture of NCGS / WS is similar to CD / IBS symptoms: abdominal pain and bloating, bowel irregularity, as well as extra-intestinal manifestations such as brain fog, headaches, myofascial pain, fatigue, dermatitis and depression.¹³

Treating GI Issues: The Four R's

Only 1 percent of Americans have confirmed celiac disease; however 0.5 percent to 6 percent is the reported prevalence of NCGD.¹³ In fact, about 25 percent of those following a GF diet do so because of CD and/or NCGS / WS. Regardless, the four R's have been demonstrated to be an effective approach to healing many gastrointestinal-related maladies.

1. Remove – offending foods such as gluten, dairy, soy, corn, and/or refined sugar; and pathogens such as Candida.
2. Replace – digestive enzymes and stomach acid supplementation to help break down food.
3. Reinoculate – prebiotics, probiotics and fermented foods.
4. Retain – long-term lifestyle changes such as consistent exercise, adequate sleep, mindful eating, meditation / stress management, and avoidance of any unnecessary over-the-counter or prescription medication.

References

1. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol, 2017 May 23;8:598.
2. Richards JL, Yap YA, McLeod KH, Mackay CR, Mariño E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunology. 2016 May 13;5(5):e82.
3. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol, 2012 Oct;10(10):1096-100.
4. Ibid.
5. Parrish CR (series editor). "Non-Celiac Gluten Sensitivity: Where Are We Now in 2015?" Nutrition Issues in Gastroenterology, Series #142, June 2015.
6. Ignacio A, Morales CI, Câmara NO, Almeida RR. Innate sensing of the gut microbiota: modulation of inflammatory and autoimmune diseases. Front Immunol, 2016 Feb 19;7:54.
7. Alexander BJ, Lord RS. "Laboratory Evaluations for Integrative and Functional Medicine." Metametrix Institute, 2012.
8. Ibid.
9. Michielan A, D'Incà R. Intestinal permeability in inflammatory bowel disease: pathogenesis, clinical evaluation, and therapy of leaky gut. Mediators Inflamm, 2015;2015:628157.
10. Campbell AW. Autoimmunity and the gut. Autoimmune Diseases, 2014:152428.
11. Brown DG, Round JL. Friends in low places: intestinal commensals limit colitis through molecular mimicry. Cell, 2017 Oct 19;171(3):503-505.
12. Catassi C, Alaedini A, Bojarski C, Bonaz B, et al. The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): an update. Nutrients, 2017 Nov 21;9(11).
13. Losurdo G, Principi M, Iannone A, Amoruso A, et al. Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm. World J Gastroenterol, 2018 Apr 14;24(14):1521-1530.
14. Parrish CR (editor), Op Cit.