A healthy immune system helps the body defend against challenges. When the immune system has trouble recognizing its own cells from foreign ones, it may lead to autoimmune conditions. More than 80 identified autoimmune conditions collectively affect more than 24 million people in the United States. (1)
With advances in research, scientists have come to appreciate the role of the gut in supporting normal immune processes and pathways. A large portion of the body's immune cells are in the gut. Additionally, we understand that the interactions of the microbiota with the intestinal epithelial barrier and immune cells can influence the immune system at a systemic level. (2)
This article describes the intricate relationship between the microbiota, intestinal immune responses, systemic immunity, and autoimmunity and outlines the importance of complementary and integrative interventions in supporting autoimmune health.
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What is Autoimmune Disease?
An autoimmune condition is any situation in which the body's immune system mistakenly targets its own healthy tissues. They are characterized by the presence of certain autoantibodies and autoreactive cells, which may lead to a predisposition to target self-tissue components. (3, 4)
Autoreactive antibodies can be present in many healthy individuals; however, chronic immune dysregulation over time may contribute to autoimmune conditions. Research has shown that autoantibodies may be present in the blood long before the development of active autoimmune conditions. These conditions can present differently between individuals, depending on the type and location of autoimmune activity. Typical signs and symptoms may include chronic fatigue, fever, muscle and joint discomfort, skin issues, digestive symptoms, and swollen lymph nodes. (3-5)
What is The Gut Microbiome?
The gut microbiome is the collection of over 100 trillion microbes, including more than one thousand species of bacteria. The development of a healthy human microbiome begins at an early age, with recent research indicating that mothers may pass bacteria to their fetuses in utero. The gut microbiome continues to develop and evolve throughout life, influenced by genetic, lifestyle, and environmental factors. (6-8)
Along with influencing normal gastrointestinal health and function, the gut microbiome plays a role in maintaining nutrient synthesis and digestion, detoxification, and immunologic balance. While specific patterns of the gut microbiome are associated with normal health and function, changes in the microbiota composition, called dysbiosis, are linked with various health challenges. (7, 9)
How Does Our Gut Microbiome Affect Autoimmune Disease?
Autoimmune conditions are thought to develop from the interplay between genetic predisposition, environmental factors, and increased intestinal permeability (or "leaky gut"). The beneficial bacteria of the gut microbiome are responsible for maintaining the epithelial barrier of the gastrointestinal tract through their production of fermentation products, like short-chain fatty acids, which help regulate the tight junctions holding intestinal cells closely together. This semi-permeable barrier allows the absorption of essential nutrients and immune sensing while restricting systemic access to foreign molecules and pathogens. (10)
Dysbiosis may create a localized inflammatory response within the mucosal surface of the gastrointestinal tract, potentially leading to the breakdown of tight junctions, epithelial barrier challenges, and increased intestinal permeability. In a leaky gut state, large food particles, toxins, and pathogens can travel from the intestines into the bloodstream, where the immune system may detect them as foreign, initiating an inflammatory immune response and the production of antibodies. If these foreign molecules resemble the body's cells, the immune system may mistakenly begin to target its own tissues, a process known as molecular mimicry. (2, 10)
The gut microbiota and immune cells are in constant communication; dysbiosis can also negatively influence the modulation of immune responses, potentially contributing to the loss of self-tolerance. Overall, chronic inflammatory reactions associated with dysbiosis may contribute to the development and progression of autoimmune conditions. (2)
Functional Medicine Labs to Test for Root Cause of Autoimmune Disease
Diagnosing autoimmune conditions can be challenging, as symptoms can be vague, remitting-relapsing, and vary between people. Functional medicine tests are available to support the diagnostic process. Alongside clinical presentation, labs that measure autoantibodies in the blood can help identify autoimmunity's presence, type, and severity. Specialty tests are valuable tools in a holistic approach to healthcare, as they can assist in identifying underlying factors of autoimmunity for personalized support and improved health outcomes.
Autoantibody Testing
Antinuclear antibodies (ANA) are antibodies that target the proteins within the nucleus of a cell. ANA is a standard screening biomarker for autoimmune conditions because elevations can indicate, but are not necessarily diagnostic for, autoimmune activity. A positive ANA is typically followed by a reflex panel, in which specific antibodies associated with autoimmune conditions are measured to narrow the differential diagnosis.
The Multiple Autoimmune Reactivity Screen (Array 5) by Cyrex Labs is a specialty panel assessing autoantibodies that may be predictive for autoimmune activity and tissue challenges. It includes autoantibodies that are not routinely measured in an ANA reflex panel, allowing for broader detection of autoimmune activity.
Comprehensive Stool Test
Comprehensive stool analyses assess the gastrointestinal tract's and gut microbiome's health, function, and integrity. Identifying dysbiosis, gastrointestinal infections, maldigestion, and intestinal inflammation can help personalize gut-supportive protocols to manage autoimmune responses.
Intestinal Permeability
Intestinal permeability, potentially caused by dysbiosis or other environmental factors, can be measured by various methods. The Intestinal Antigenic Permeability Screen (Array 2) by Cyrex Labs is a blood test that measures intestinal permeability to large molecules and identifies the route through the intestinal barrier. It can be bundled with their Irritable Bowel/SIBO Screen (Array 22), which identifies large and small intestinal bacterial overgrowth and evaluates the release of bacterial toxins that can affect the intestinal barrier.
Zonulin is a protein secreted by the intestinal tract and is the only known reversible regulator of intestinal permeability by control of the intestinal tight junctions. Zonulin can be measured in a blood or stool sample, and elevations may indicate increased intestinal permeability.
Food Sensitivities
Food sensitivities have been linked with the onset and progression of leaky gut, and certain food triggers, such as gluten, are associated with specific autoimmune conditions, like celiac disease and Hashimoto's thyroiditis. Food triggers identified on a sensitivity panel can be considered for elimination from the diet to support gut health, manage inflammation, and support the immune system.
The Wheat/Gluten Proteome Reactivity & Autoimmunity Screen (Array 3X) by Cyrex Labs assists in identifying wheat-related autoimmune conditions. For those with non-celiac gluten sensitivity (NCGS) or celiac disease not responding to a gluten-free diet, their Gluten-Associated Cross-Reactive Foods and Foods Sensitivity Profile (Array 4) examines sensitivities to additional dietary proteins and foods that often cross-react with gluten.
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Complementary and Integrative Medicine Treatment for Autoimmune Disease
Complementary and integrative medicine (CIM) is a root-cause approach to healthcare. CIM therapies can be implemented to help manage symptoms and holistically address the underlying factors of health challenges. Conventional pharmacotherapy may be a necessary aspect of an autoimmune management protocol to support tissue/organ health; CIM modalities may augment their effects and potentially reduce their necessity in long-term management by addressing underlying health factors.
Nutrition for Autoimmune Disease
Functional nutritional therapies are one aspect of an integrative approach to autoimmune conditions through identifying, eliminating, and addressing food sensitivities, nutrient needs, and dysbiosis that may contribute to autoimmune activity.
The Autoimmune Protocol (AIP) diet is a modified Paleolithic (Paleo) diet, which encourages the consumption of uncultivated plants and wild-sourced animal foods. The AIP is a three-phase elimination protocol that aims to address inflammatory dietary patterns and food additives and incorporate foods that meet nutritional needs, support the gut microbiota, regulate the immune response, and promote gastrointestinal health. In addition to dietary modifications, the AIP emphasizes the formation of healthy lifestyle habits, like sleep hygiene, physical activity, and stress management. Clinical studies have shown positive outcomes of the AIP diet on inflammatory bowel disease (IBD) and Hashimoto's thyroiditis. (11, 12)
Supplements and Herbs for Autoimmune Disease
In addition to dietary patterns and other lifestyle habits, many evidence-based dietary and botanical supplements are used to support individuals with autoimmune conditions. Some of the supplements often considered by functional medicine practitioners are outlined below.
Probiotics
Probiotic supplements may promote a healthy composition of beneficial bacteria in the gut microbiome, thereby supporting epithelial barrier function, managing inflammation, and modulating immune responses. Clinical trials have associated probiotic supplementation with improved gastrointestinal symptoms, systemic inflammation, and disease activity in various autoimmune conditions, including IBD, rheumatoid arthritis, and multiple sclerosis. (13-15)
Antimicrobial Herbs
Antimicrobial herbs, often used alongside probiotics, may help manage bacterial and fungal overgrowth that could contribute to activated immune responses. Berberine is one such example. A compound found in some plants, including barberry, goldenseal, and Oregon grape, berberine has been shown to influence the expression of inflammatory cytokines, manage inflammation, and support the synthesis of butyrate, a short-chain fatty acid that enhances intestinal barrier function.
Curcumin
Curcumin is the primary bioactive compound of turmeric, known for its natural anti-inflammatory properties. Curcumin may influence immune cells to help manage inflammatory pathways and symptoms, like joint swelling and stiffness, associated with autoimmune conditions. (15-17)
Additionally, curcumin may support the gut microbiome and reduce intestinal permeability by modulating tight junction proteins (18).
Vitamin D
Vitamin D plays a role in gene expression and regulating immune responses, two critical aspects of autoimmune condition development. Studies have linked vitamin D levels to various autoimmune conditions, including insulin-dependent diabetes mellitus, multiple sclerosis, IBD, lupus, and rheumatoid arthritis. Research suggests vitamin D supplementation may be associated with autoimmune condition management, reduced disease activity, and lower fatigue levels. (12, 15)
Omega-3 Fatty Acids
Omega-3 fatty acids possess properties that may help manage inflammation and support immune function. Commonly sourced from fish oil, omega-3 fatty acids have been shown to support quality of life, manage disease activity and symptom severity, and reduce the need for anti-inflammatory medications in individuals with various types of autoimmune conditions. (15, 18)
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Summary
Autoimmune conditions are complex and multifactorial, characterized by chronic immune dysregulation and challenges in self-tolerance. As scientists continue to research and understand the intricacies of the human microbiome, the role of these mutualistic microbes within the gastrointestinal tract in supporting a healthy intestinal barrier and immune signaling becomes increasingly clear. Dysbiosis is considered an underlying factor in intestinal permeability, immune dysregulation, and autoimmunity.
Functional medicine testing and CIM modalities are valuable aids in a holistic approach to evaluating and managing autoimmune conditions by identifying imbalances in the relationship between microbiota and immune system function. Supporting a healthy microbiome is a crucial component of an integrative approach to autoimmune health.
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