Gut Health

Tiffany Eberhard
HBSc, ND
https://www.tiffanyeberhardnd.com
7 May 2015

Language English

Autoimmunity

The immune system is able to discriminate self from non-self antigens, substances that trigger the immune system, which protects the host from infections and cancer. Autoimmune diseases are characterized by deregulated immune responses ^[1]. Autoimmune diseases affect 5-8% of the population in the United States and can affect almost every site in the body ^[2]. The disease process is either cell mediated, TH1 cells, or mediated by auto-antibodies. However, it is now known that cytokines, chemokines, adhesion molecules, and other components of inflammatory response also mediate tissue damage in autoimmune diseases ^[1]. Additionally, an imbalance between TH1 and TH2 immune responses are important in understanding how autoimmune diseases develop ^[2]. Autoimmune diseases involve tissue damage and loss of function due to an immune response directed against specific organs. There are several conditions that lead to the development of autoimmunity. The first is genetic susceptibility of the immune system to recognize and misinterpret an environmental antigen present within the gastrointestinal tract. Secondly, the host must be exposed to the antigen or substance. Lastly, the gastrointestinal mucosal immune system must be exposed to the antigen, which is normally prevented by an intact intestinal barrier ^[3].

Intestinal Permeability

The intestinal mucosal barrier is a single layer of cells that lines the gut, which consists of mainly intestinal cell membranes and tight junctions between the cells. Tight junctions are made up of a complex meshwork of proteins and must be able to respond rapidly and in a coordinated way to keep up with the diverse physiological challenges to which they are subjected ^[3]. Zonulin is an important molecule that reversibly modulates tight junction permeability ^[2]. The intestinal epithelium acts as a selective barrier and allows the transport of essential dietary nutrients, electrolytes, and water to cross and enter circulation while preventing the passage of harmful substances ^[4]. Dysregulation of this barrier can occur due to stress, invasion of organisms, infection, and immunological challenges associated with various diseases. Intestinal barrier integrity is critical for the absorption of nutrients and overall health. Barrier dysfunction is associated with increased intestinal permeability and the development of gastrointestinal diseases as well as various autoimmune diseases ^[5]. Alteration in intestinal permeability related to changes in tight junction competency is involved in the fast growing number of autoimmune diseases. Increased intestinal permeability appears to occur before disease development and causes an abnormality in antigen delivery that triggers the multi-organ process leading to the autoimmune response. The gut-associated lymphoid tissue (GALT) prevents potentially harmful intestinal antigens from entering systemic circulation and is involved with tolerance to antigens. The balance between immunity and tolerance is critical for a healthy intestine while abnormal or inappropriate immune responses can result in inflammatory pathologies ^[2].

Autoimmune diseases linked to intestinal permeability

The following conditions outlined below all involve increased intestinal permeability and incompetent tight junctions that allow antigens to pass the intestinal barrier. These antigens challenge the immune system to produce an immune response that can target any organ or tissue in genetically predisposed individuals ^[3].

Celiac disease

Celiac disease is an immune-mediated chronic intestinal disease that has multiple manifestations that vary in severity. It is triggered by gliadin ingestion, which is a protein found in wheat, and leads to small bowel inflammation due to the immune reaction. Celiac disease is considered a systemic disease that can cause injury to any organ. The continuous presence of inflammatory mediators causes further permeability across the intestinal epithelium ^[3].

Type 1 Diabetes Mellitus

Type 1 Diabetes is a complex condition, which involves increased intestinal permeability, altered immune responses, as well as an altered gut flora ^[6]. It has been suggested that increased permeability of the intestinal tight junctions is responsible for both the onset of Type 1 diabetes as well the gastrointestinal symptoms that are often experienced in Type 1 diabetics ^[3].

Multiple Sclerosis

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath of nerve cells. The resulting damage disrupts the communication between the brain and the body ^[7]. It has been shown that multiple sclerosis patients may experience increased permeability of tight junctions in addition to their increase in blood-brain barrier permeability, which can contribute to their symptoms ^[3].

Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a common rheumatic disorder that affects young and middle-aged adults. It involves stiffness and pain in the back and has been linked to increased intestinal permeability and inflammation ^[3]. Up to 70% of people with AS have some intestinal inflammation while some progress to more severe forms of inflammation similar to the form seen in patients with inflammatory bowel diseases. Research has demonstrated intestinal dysbiosis in patients with AS versus healthy control subjects. Therefore, treatment of AS should involve addressing this dysbiosis and intestinal permeability ^[8].

Asthma

Asthma is a disease in which T cells cause inflammation and therefore constriction within the bronchus. However, a relationship exists between asthma and the gastrointestinal tract ^[9]. Research has demonstrated that asthmatics have increased intestinal permeability, which may play a role in susceptibility to environmental allergens ^[3].

Inflammatory Bowel Disease

Inflammatory bowel diseases (IBD) include Ulcerative Colitis and Crohn’s Disease. There are multiple molecular mechanisms that cause increased intestinal permeability in patients with IBD, such as altered tight junction protein expression and increased epithelial cell death. The breakdown in the protective barrier in patients with IBD leads to inflammation and enhanced production of cytokines and other mediators that can further contribute to a dysfunctional barrier ^[4].

Naturopathic Approaches

Eliminate food sensitivities

What we eat affects our intestinal permeability and therefore autoimmune diseases. Removing foods from the diet that cause inflammation and impair the intestinal barrier can potentially alleviate symptoms and in some cases resolve autoimmune diseases. Some common food sensitivities are gluten, dairy, and vegetables from the nightshade family, such as peppers, tomatoes, and potatoes. It is also important to avoid food additives and processed foods since it is known that chemicals in these foods damage tight junctions and therefore increase intestinal permeability ^[10].

Probiotics

Bacteria are crucial in shaping the immune response and therefore probiotics can have an effect on intestinal permeability ^[2]. Certain harmful gut bacteria affect T-cell populations and can control the development of autoimmune diseases in various organs in the body. Diet can have a profound immunomodulatory effect through its ability to alter gut microflora and it has been shown that modifying the diet can quickly change the microbiota composition. It is becoming clear that particular species of gut bacteria are required for regulating immune responses and therefore changes in the microbiota can result in a lack of immune regulation and inflammation. Additionally, stress impacts the immune and metabolic systems and can alter gut microbiota. Inflammation can damage the microbiota and create an ideal environment for more pathogenic bacteria ^[11]. Intestinal immune response dysregulation to normal bacterial flora may play a crucial role in inflammatory and autoimmune diseases ^[12].

Glutamine

Glutamine is a non-essential amino acid that is important in intestinal cell function and is the main fuel of intestinal cells ^[5,13]. It enhances intestinal and whole-body growth, promotes intestinal cell proliferation and survival, and regulates intestinal barrier function in injury, infection, stress, and other catabolic conditions. Glutamine increases protein synthesis in intestinal cells, promotes intestinal development, regulates tight junction protein expression and intestinal immunity, and inhibits cell death induced by oxidative stress. Being deprived of glutamine results in increased intestinal permeability and reduced tight junction proteins ^[5]. One study found significant improvement in intestinal permeability after glutamine supplementation in people with Crohn’s Disease ^[13].

Quercetin

Quercetin is a bioflavonoid that exhibits anti-inflammatory activity. Studies have shown that exposing intestinal epithelial cells to quercetin enhances their barrier function through the activation/inactivation of intracellular signaling molecules that modulate permeability and tight junction proteins. Supplementing with quercetin and/or ensuring sufficient intake from food may have protective and beneficial effects on intestinal permeability ^[14].

Curcumin

Curcumin is a powerful anti-inflammatory agent that impairs the NF-kappa beta signaling pathway. This signaling pathway plays an important role in immune and inflammatory responses. Type 1 Diabetes Mellitus is an autoimmune disease that arises from the selective and progressive loss of insulin-producing beta cells. Studies have demonstrated that curcumin modulates key immune cells involved in the attack against beta cells. It attenuates immunity and can delay or prevent diabetes onset ^[15]. Curcumin suppresses blood glucose levels in diabetics by increasing the antioxidant status of pancreatic beta-cells ^[16] Curcumin improves the permeability of the intestinal mucosa, reduces damage, and protects the barrier function and therefore can be used in various inflammatory and autoimmune diseases ^[17].

Conclusion

In conclusion, optimal intestinal barrier function is crucial for overall health. Abnormal intestinal permeability plays a critical role in the pathogenesis of several autoimmune diseases ^[18]. Using natural approaches to heal the intestine, address immune dysfunction and inflammation, as well as identifying any food sensitivities can help reduce symptoms, slow disease progression, and potentially decrease the likelihood of developing autoimmune diseases in susceptible individuals.

References :

Bright JJ. Curcumin and Autoimmune Disease. Advanced Experimental Medical Biology 2007;595:425-51.
Fasano A and Shea-Donohue T. Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nature Clinical Practice: Gastroenterology and Hepatology 2005;2(9):416-422.
Fasano A. Leaky Gut and Autoimmune Diseases. Clinical reviews in allergy immunology 2012;42:71-78.
Groschwitz KR and Hogan SP. Intestinal barrier function: Molecular regulation and disease pathogenesis. Clinical reviews in allergy and immunology 2009;124(1):3-22.
Wang B et al. Glutamine and intestinal barrier function. Amino Acids 2014.
Vaarala O, Atkinson MA, Neu J. The “Perfect Storm” for Type 1 Diabetes The Complex Interplay Between Intestinal Microbiota, Gut Permeability, and Mucosal Immunity. Diabetes 2008;l57(10):2555-2562.
Mayo Clinic. Multiple sclerosis, 2014. http://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/basics/definition/con-20026689
Costello ME et al. Microbes, the gut and akylosing spondylitis. Arthritis Research and Therapy 2013;15(3):214.
Hijazi Z et al. Intestinal permeability is increased in bronchial asthma. Arch Dis Child 2004;89(3):227-229.
Lerner A and Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015.
Kranich J, Maslowski KM, Mackay CR. Commensal flora and the regulation of inflammatory and autoimmune responses. Semin Immunol 2011;23(2):139-145.
Tlaskalova-Hogenova H et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases). Immunol Lett 2004;93(2-3):97-108.
Benjamin J et al. Glutamine and Whey Protein Improve Intestinal Permeability and Morphology in Patients with Crohn’s Disease: A Randomized Controlled Trial. Dig Dis Sci 2012;57(4):1000-1012.
Suzuki T and Hara H. Quercetin Enhances Intestinal Barrier Function through the Assembly of Zonnula Occludens-2, Occludin, and Claudin-1 and the Expression of Claudin-4 in Caco-2 Cells. Journal of Nutrition 2009;139(5):965-974.
Castro CN et al. Curcumin ameliorates autoimmune diabetes. Evidence in accelerated murine models of type 1 diabetes. Clin Exp Immunol 2014;177(1):149-160.
Shehzad A, Rehman G, Lee YS. Curcumin in Inflammatory Diseases. BioFactors 2013;39(1):69-77.
Aggarwal BB et al. Curcumin Protects Intestinal Mucosal Barrier Function of Rat Enteritis via Activation of MKP-1 and Attenuation of p38 and NF-kB Activation. British Journal of Pharmacology 2013;169(8):1672-1692.
Teshima CW and Meddings JB. The Measurement and Clinical Significance of Intestinal Permeability. Current Gastroenterology Reports 2008;10:443-449.

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