A healthy immune system defends the body against infection and disease. The immune system's failure to recognize self-cells from foreign ones results in autoimmune disease. More than 80 identified autoimmune diseases 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 modulating normal immune processes and pathways. 70-80% 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 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 autoimmune prevention and treatment.

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What is Autoimmune Disease?

An autoimmune disease is any condition in which the body's immune system mistakes its own healthy tissues as foreign and attacks them. They are defined by pathogenic autoantibodies, autoreactive T helper-1 and T helper-17 cells, and their loss of self-tolerance, or predisposition to attack self-tissue components. (3, 4)

Autoreactive antibodies are present in most healthy individuals; but it is chronic immune dysregulation over time causes autoimmune disease. In fact, research has shown that autoantibodies may be present in the blood from 3 months to 19 years before the development of active autoimmune disease. Active autoimmune disease presents differently between individuals, depending on the type and location of autoimmune activity. Typical signs and symptoms of the disease include chronic fatigue, fever, muscle and joint pain and swelling, skin problems, 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 belonging predominantly to the Bacteroidetes and Firmicutes phyla. The development of a healthy human microbiome develops at an early age, with recent research indicating that mothers begin passing bacteria to their fetuses in utero. The gut microbiome continues to develop and evolve throughout the lifespan, influenced by genetic, lifestyle, and environmental factors. (6-8)

Along with influencing normal gastrointestinal health and function, the gut microbiome is essential in maintaining nutrient synthesis and digestion, detoxification, and immunologic homeostasis. Whereas specific homeostatic patterns of the gut microbiome are associated with normal health and function, alterations in the microbiota composition, called dysbiosis, are linked with diseases. (7, 9)

How Does Our Gut Microbiome Affect Autoimmune Disease?

Autoimmune diseases are thought to develop from the interplay between genetic predisposition, environmental triggers, and increased intestinal permeability (or "leaky gut"). The beneficial commensal 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 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 creates a localized inflammatory response within the mucosal surface of the gastrointestinal tract, leading to the breakdown of tight junctions, epithelial barrier dysfunction, 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 detects them as foreign, initiating an inflammatory immune response and the production of antibodies. If these foreign molecules look similar to the body's cells, the immune system may mistakenly begin to target and attack its own tissues, leading to autoimmunity. This process is called molecular mimicry. (2, 10)

The gut microbiota and immune cells are in constant bidirectional communication; dysbiosis can also negatively influence the modulation of innate and adaptive immune responses, creating an imbalance between the helper T cell subtypes and contributing to the loss of self-tolerance. Overall, chronic inflammatory reactions induced by dysbiosis strongly contribute to the development and progression of autoimmune diseases. (2)

Functional Medicine Labs to Test for Root Cause of Autoimmune Disease

Diagnosing autoimmune diseases 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 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 causes of autoimmunity for treatment personalization and improved health outcomes.

Autoantibody Testing

Antinuclear antibodies (ANA) are antibodies that attack the proteins within the nucleus of a cell. ANA is a standard screening biomarker for autoimmune disease because elevations can indicate, but are not necessarily diagnostic for, autoimmune disease. A positive ANA is typically followed by a reflex panel, in which specific antibodies associated with autoimmune diseases are measured to narrow the differential diagnosis.

The Multiple Autoimmune Reactivity Screen (Array 5) by Cyrex Labs is a specialty panel assessing autoantibodies predictive for autoimmune disease and tissue damage. 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-healing protocols to dampen autoimmune responses.

Intestinal Permeability

Intestinal permeability, 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 damaging 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 breach 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 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 highly associated with specific autoimmune diseases, like celiac disease and Hashimoto's thyroiditis. Food triggers identified on a sensitivity panel can be eliminated from the diet to heal leaky gut, reduce inflammation, and reset the immune system.

The Wheat/Gluten Proteome Reactivity & Autoimmunity Screen (Array 3X) by Cyrex Labs assists in identifying wheat-related autoimmune diseases. 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 medicine. CIM therapies can be implemented to palliate symptoms and holistically address the underlying causes of disease. Conventional pharmacotherapy may be a necessary aspect of an autoimmune treatment protocol to prevent irreversible tissue/organ damage; CIM modalities augment their effects and potentially reduce their necessity in long-term management by correcting underlying disease triggers.

Nutrition for Autoimmune Disease

Functional nutritional therapies are one aspect of an integrative treatment approach to autoimmune diseases through identifying, eliminating, and correcting food sensitivities, nutrient deficiencies, and dysbiosis contributing to autoimmune pathology.

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 eliminate inflammatory dietary patterns and food additives and incorporate foods that meet nutritional needs, rebalance the gut microbiota, regulate the immune response, and promote gastrointestinal healing. 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 clinical 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 shown effective in treating autoimmunity. Some of functional medicine doctors' most routinely prescribed supplements are outlined below.

Probiotics

Probiotic supplements promote a healthy composition of beneficial bacteria in the gut microbiome, thereby improving epithelial barrier function, reducing inflammation, and modulating localized and systemic 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, can treat identified bacterial and fungal overgrowth contributing to activated systemic immune responses. Berberine is one such example. A potent antimicrobial chemical found in some plants, including barberry, goldenseal, and Oregon grape, berberine has been shown to inhibit the expression of inflammatory cytokines, reduce systemic inflammation, and promote the synthesis of butyrate, a short-chain fatty acid that enhances intestinal barrier function.

Curcumin

Curcumin is the primary bioactive compound of turmeric, a well-known natural potent anti-inflammatory agent. Curcumin strongly influences immune cells to downregulate inflammatory pathways and symptoms, like joint swelling and stiffness, associated with autoimmune diseases. (15-17)

Additionally, curcumin supports the gut microbiome and reduces intestinal permeability by modulating tight junction proteins (18).

Vitamin D

Vitamin D plays a key role in gene expression and regulating immune responses, two critical aspects of autoimmune disease development. Studies have linked vitamin D deficiency to various autoimmune diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, IBD, lupus, and rheumatoid arthritis. Research suggests vitamin D supplementation is associated with autoimmune disease prevention, reduced disease activity, and lower fatigue levels. (12, 15)

Omega-3 Fatty Acids

Omega-3 fatty acids possess anti-inflammatory and immunomodulatory effects that can regulate gene and inflammatory cytokine expression. Commonly dosed through fish oil, supplementation of omega-3 fatty acids has been shown to improve quality of life, reduce disease activity and symptom severity, and reduce the need for anti-inflammatory medications in patients with various types of autoimmune diseases. (15, 18)

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Summary

Autoimmune diseases are complex multifactorial diseases characterized by chronic immune dysregulation, loss of self-tolerance, and the destruction of the body's tissues. As scientists continue to research and understand the intricacies of the human microbiome, the role of these mutualistic bugs homed within the gastrointestinal tract in regulating a healthy intestinal barrier and immune signaling becomes exceedingly clear. Dysbiosis is an underlying trigger of intestinal permeability, immune dysregulation, and autoimmunity.

Functional medicine testing and CIM modalities are valuable aids in a holistic approach to evaluating and successfully managing autoimmune diseases by identifying imbalances in the entanglement between microbiota and immune system function. Without a doubt, supporting a healthy microbiome is a crucial component of an integrative autoimmune protocol.