Table of contents

What is an autoimmune disease?

An autoimmune disease is a pathological immunological condition in which the immune system’s tolerance is disrupted, and the body begins to recognize its own cells, tissues, or organs as foreign. This triggers a targeted immune response that leads to chronic inflammation and tissue damage. [1]

Figure 1: Definition of autoimmune disease

Main characteristics of autoimmune diseases [2]:

1. An imbalance between effector T cells (responsible for initiating the immune response) and regulatory T cells (responsible for suppressing the immune response).
2. Insufficient elimination or improper control of autoreactive immune cells, which are capable of attacking the body’s own cells and tissues.
3. A chronically activated, persistently “alert” immune system that shows heightened reactivity even to harmless stimuli.
4. The presence of systemic or locally widespread inflammatory processes.

There are currently more than 80 different autoimmune diseases. Some are well-known, such as type 1 diabetes and multiple sclerosis, while others are rare and difficult to diagnose. [3]

The incidence of autoimmune diseases is significantly higher in women. This can be explained, in part, by the immunosuppressive effect of the higher testosterone levels found in men, and also by the increased production of B cells (immune cells that can become self-reactive), which may trigger autoimmune reactions. [4]

Figure 2: Main characteristics of autoimmune diseases

Environmental triggers of autoimmune diseases

Caesarean section

The intestinal tract of infants born via caesarean section is mainly colonized by bacteria from the mother’s skin, the skin of medical personnel (e.g., doctors, nurses), and the hospital environment, including Staphylococcus species. In contrast, babies delivered vaginally receive bacteria from the mother’s vaginal flora, including beneficial Lactobacillus strains.

Research findings indicate that the abnormal gut microbiome composition in babies born by C-section may influence immune system development and, over time, increase the risk of asthma, allergic diseases, and certain autoimmune conditions. [10–11]

Environmental toxins

Environmental toxins are major risk factors for developing autoimmune diseases. Mercury, a heavy metal found in some seafood and in dental amalgam fillings, alters gene expression in the immune system and may trigger autoimmune responses. [12]

BPA, a widely used plasticizer found in cash register receipts and plastic food containers, can disrupt cytochrome P450 detoxification pathways, increase circulating lipopolysaccharide (LPS) levels, and activate macrophages, thereby provoking autoimmune responses. [13]

Phthalates, another common group of plasticizers, may trigger thyroid autoimmunity by increasing oxidative stress. [14]

Organic solvents, which are present in dry cleaning chemicals, paint thinners, nail polish removers, and various detergents, raise the risk of autoimmune disease by causing inflammation and tissue damage. [15]

Excessive cleanliness

Early-life microbial exposure is necessary for the immune system to learn to distinguish between self and non-self. Without exposure to microbial substances—such as environmental bacteria and contaminants—the immune system cannot develop properly. Our society’s obsession with disinfecting, scrubbing, and vacuuming to eliminate every trace of dirt removes critical microbial exposure from children’s environments. This deprives their developing immune systems of the chance to learn properly, increasing the risk of future immune system dysfunction. [16]

Gluten

Celiac disease is the most well-known autoimmune disorder caused by gluten. However, gluten may also play a role in certain non-celiac autoimmune diseases, such as Hashimoto’s thyroiditis and Sjögren’s syndrome. The main cause is that gluten can trigger inflammation, alter the gut microbiome, and increase intestinal permeability. [17]

Infections

Although a lack of microbial exposure contributes to the development of autoimmune diseases, chronic infections caused by pathogenic microbes also play a significant role. Chronic Lyme disease can provoke autoimmune reactions in the heart, blood vessels, and joints. This is due to molecular mimicry between Borrelia burgdorferi and the host’s own antigens [18–19]. Helicobacter pylori infection has been associated with autoimmune thyroid disease, while cytomegalovirus infection may worsen autoimmune-related neuroinflammation [20–21]. In many cases, proper treatment of these infections is essential to reversing or mitigating autoimmune processes.

Mitochondrial dysfunction

Mitochondrial dysfunction plays a role in the development and progression of several autoimmune diseases, including multiple sclerosis (MS) and lupus [22–23]. In addition to producing energy, mitochondria regulate autophagy—a cellular process responsible for breaking down and recycling damaged components. When mitochondria malfunction, autophagy is impaired, which can contribute to the onset of autoimmune disease.

Chronic stress

Psychological stress is a well-established risk factor for autoimmune diseases [24]. Stress influences immune responses by disrupting the gut microbiome and dysregulating the hypothalamic-pituitary-adrenal (HPA) axis, which is the body’s primary stress response system. [25]

Circadian rhythm disruption

The activity of immune cells is strongly influenced by the circadian rhythm, a set of biological processes that follow a 24-hour cycle and regulate both behavior and physiology. Factors that disrupt this rhythm contribute to immune dysfunction. Studies show that rotating shift work, which significantly disturbs the circadian rhythm, is linked to autoimmune hypothyroidism and rheumatoid arthritis [26–27]. Circadian rhythm disturbances may also be involved in the development of central nervous system autoimmune diseases such as multiple sclerosis. [28]

Sleep deprivation

Sleep deprivation, which is closely linked to disturbances arising from circadian rhythm disruption, increases the risk of developing autoimmune diseases. Both chronic insomnia and sleep apnea are associated with a significantly elevated risk of autoimmune diseases. [29–30]

Figure 3: Environmental triggers of autoimmune diseases

Nine common autoimmune diseases

1. Celiac disease

Celiac disease is an autoimmune condition in which gluten proteins—found in grains such as wheat—trigger an immune response that damages the small intestine. The condition arises from a combination of genetic predisposition, especially HLA-DQ2 and HLA-DQ8 polymorphisms, and other non-genetic factors. [31]

The widespread use of antibiotics is considered a major contributor to the rising incidence of celiac disease in industrialized countries. This is due to the harmful effects of antibiotics on the intestinal flora.

2. Hashimoto’s disease

Hashimoto’s disease occurs when the immune system produces antibodies that attack the thyroid gland. This results in reduced thyroid hormone production and leads to hypothyroidism. Gluten appears to play a significant role in the development of Hashimoto’s disease. Many people with Hashimoto’s also suffer from celiac disease, and following a gluten-free diet often leads to clinical improvement. [32–33]

Helicobacter pylori infection may also contribute to the development of Hashimoto’s disease. A particularly virulent strain of H. pylori, known as CagA-positive H. pylori, has been found in individuals with Hashimoto’s. Treating the infection has been shown to reduce thyroid autoantibodies [20]. Researchers believe that CagA-positive H. pylori may trigger autoimmune thyroid dysfunction because its genetic sequence closely resembles that of thyroperoxidase, an enzyme involved in thyroid hormone synthesis.

3. Graves’ disease

In Graves’ disease, the immune system produces antibodies that activate the thyroid-stimulating hormone receptor (TSHR). This causes the thyroid gland to become overactive and leads to hyperthyroidism. As in Hashimoto’s disease, H. pylori infection is believed to play a role in the development of autoimmune hyperthyroidism. [20]

4. Rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disease that causes severe swelling and pain in the joints. It is associated with changes in the gut microbiota. It has also been linked to a number of infectious agents, including Porphyromonas gingivalis (a bacterium that causes periodontitis), Epstein-Barr virus, and Mycoplasma bacteria. [34]

5. Multiple sclerosis

Multiple sclerosis (MS) is a disease in which the immune system attacks proteins in the myelin sheath that insulates neurons. This leads to demyelination and eventually to neuron death. The development of MS is influenced by several factors, including changes in the gut microbiota, leaky gut, gluten sensitivity, and mitochondrial dysfunction.

People with MS have lower levels of anti-inflammatory gut bacteria compared to healthy individuals. They also show increased intestinal permeability [35]. These gut alterations interfere with the differentiation of regulatory T cells, increasing the risk of autoimmunity [35–36]. Acinetobacter calcoaceticus, an intestinal bacterium generally considered commensal, is found in elevated amounts in people with MS. This bacterium produces peptides that mimic myelin proteins in their amino acid sequences. These peptides can trigger an autoimmune response. [37]

Several clinical studies suggest that gluten sensitivity may contribute to the development or worsening of MS. A gluten-free diet has been associated with a significant reduction in symptoms. [38]

Mitochondrial dysfunction is also considered a key factor in MS progression. Impaired energy production reduces ATP levels in nerve cells. ATP plays a fundamental role in storing and transferring energy between cells. [38–39]

6. Type 1 diabetes

Type 1 diabetes develops when the immune system attacks and destroys the insulin-producing beta cells in the pancreas. This leads to insufficient insulin production. The condition is associated with several HLA gene polymorphisms, as well as at least 40 non-HLA genetic variants [40]. Additional contributing factors include impaired gut barrier function, antibiotic use, disruptions in the gut microbiota, and gluten consumption. [41–44]

7. Inflammatory bowel disease

Inflammatory bowel disease (IBD) is a term used to describe chronic inflammatory disorders of the gastrointestinal tract. The two main types are Crohn’s disease and ulcerative colitis. Individuals with IBD show significant dysbiosis of the gut microbiome, including higher levels of opportunistic pathogenic bacteria and fungi [45]. The use of antibiotics is also strongly associated with the development of IBD. [46]

Non-celiac gluten sensitivity may play a role in IBD, as gluten can trigger intestinal inflammation [47]. In addition, non-gluten compounds found in wheat and other grains—such as alpha-amylase/trypsin inhibitors—can activate toll-like receptor 4, which is involved in immune activation. This leads to the upregulation of pro-inflammatory cytokines, contributing to autoimmune bowel conditions. [48]

8. Lupus

Systemic lupus erythematosus (SLE), often called lupus, is an autoimmune disease characterized by persistent inflammation and tissue damage affecting multiple organs. Lupus is associated with changes in the gut microbiome, including reduced microbial diversity and an increase in opportunistic pathogens [49]. The disease is also marked by hypersensitivity to normal gut microbes.

Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) are components of the cell walls of Gram-negative and Gram-positive gut bacteria, respectively. These substances have pro-inflammatory and immunomodulatory properties. Elevated levels of LPS have been particularly linked to the development of lupus. LPS increases systemic inflammation and stimulates autoimmune activation. [50]

Dysregulation of inflammatory pathways, including the activation of NLRP3 and AIM2 inflammasomes, may also play a role in lupus pathogenesis. [51]

9. Sjögren’s syndrome

Sjögren’s syndrome is an autoimmune disease that primarily affects the tear and salivary glands. This results in decreased tear and saliva production, causing dry eyes and dry mouth. The condition often occurs alongside other autoimmune diseases such as rheumatoid arthritis or lupus.

Studies suggest that individuals with Sjögren’s syndrome may have an increased inflammatory response to gluten. This suggests that gluten consumption could contribute to disease onset or symptom severity [52]. Microbiome studies in patients with Sjögren’s syndrome have revealed a higher proportion of opportunistic pathogens, indicating a state of gut microbial imbalance.

How can we prevent the development of autoimmune diseases?

Although we cannot change our genetic makeup, we can reduce our own—and our children’s—risk of developing autoimmune diseases by minimizing exposure to environmental factors that act as triggers for autoimmune processes.

Reducing the use of antibiotics

It is well known that antibiotics are often overprescribed in modern society. Overuse of antibiotics can contribute to the development of autoimmune diseases by reducing the body’s exposure to beneficial microbes that are crucial for immune system development. Antibiotics also disrupt the gut microbiota. Research shows that doctors frequently prescribe antibiotics in cases where they are not necessary. For this reason, we need to make conscious decisions to limit their use [53]. Antibiotics should only be used when absolutely necessary, keeping in mind that they are ineffective against viral infections, such as influenza and many common colds or upper respiratory tract infections.

Increase exposure to bacteria in early life

While an overly sterile environment in infancy and early childhood may increase the risk of developing autoimmune diseases later in life, greater exposure to microbes during this period can significantly reduce the risk.

• Use green cleaning products at home. Replace cleaning products that contain synthetic antimicrobials with natural, enzyme-based or essential oil-based alternatives. Synthetic ingredients like triclosan disrupt the gut microbiota and impair the immune response [54]. Triclosan also contributes to mitochondrial dysfunction, which plays a role in the development of autoimmune diseases. [55]
• Spend more time outdoors. Time spent in natural environments exposes the body to a wide variety of microbes, which supports the development of a strong immune system. [56]
• Living with a dog. Children who live with a dog during infancy have been shown to have lower rates of allergies. [57]

It is important to emphasize that microbial exposure needs to be continuous throughout early childhood in order for the immune system to develop properly. Children who are raised in overly hygienic environments and only occasionally come into contact with pets may actually experience worsened allergic or inflammatory responses. This likely occurs because their immune systems are not prepared for sudden exposure to microbial stimuli.

Although increased microbial exposure in adulthood is still beneficial for gut health, it does not provide the same level of immune system education as early-life exposure. Nevertheless, following these guidelines helps maintain a healthier gut flora, which plays a critical role in protection against autoimmune diseases.

Avoid processed foods

Processed foods promote the development of autoimmune diseases by damaging both metabolic and immune pathways [58]. In addition to avoiding processed foods in general, identifying and eliminating foods that trigger inflammation—such as gluten—can further reduce the risk of autoimmune conditions. [44]

Eliminate toxins

Avoiding exposure to environmental toxins is essential for reducing the risk of autoimmune activity. Tap water often contains environmental contaminants, so it may be worthwhile to invest in a high-quality water filter for both drinking and bathing. Cookware made of aluminum or coated with Teflon can leach heavy metals or toxic chemicals into food. Instead, use cast iron, enameled cast iron, or stainless steel alternatives. Mold and mycotoxins in the home severely impair immune function and may contribute to the onset of autoimmune diseases. Keeping your home free of mold is essential for maintaining immune health.

Figure 4: Prevention of autoimmune diseases

The protective effect of breastfeeding

Studies show that breastfeeding has a strong protective effect against the development of autoimmune diseases in children. Breast milk helps shape the infant’s immune system by transferring immune cells from mother to child and promoting immune tolerance. This process can reduce the future risk of autoimmune disease.

Interestingly, the combination of breastfeeding and daycare is associated with a lower risk of developing type 1 diabetes, whereas daycare without breastfeeding is linked to a higher risk [59]. This suggests that breastfeeding and early exposure to environmental microbes may work synergistically to support healthy immune development in infants.

Genetic factors influencing autoimmunity

Autoimmune diseases arise from a combination of genetic and environmental factors. Genetics can be thought of as the fuel, and the environment as the lighter. Specific gene variations, known in scientific literature as polymorphisms, lay the foundation for autoimmunity by altering the regulation of immune cells. Environmental factors then interact with these genetic predispositions, igniting the fuel and triggering the onset of autoimmune disease. Research has identified several genetic polymorphisms and environmental triggers that play a role in the development of these conditions.

The most well-known genetic risk factors for autoimmune diseases are human leukocyte antigen (HLA) polymorphisms [60]. The HLA system plays a vital role in presenting antigens (such as toxins or foreign proteins) to the immune system. Variations in HLA genes can impair the ability to present antigens properly, which increases the risk of autoimmunity. Examples of well-established HLA associations include: HLA-DQ2 and HLA-DQ8, which are associated with celiac disease. HLA-DRB1, which is linked to rheumatoid arthritis. HLA-B27, which is related to spondyloarthritis. In addition to HLA polymorphisms, variations in genes that control cytokine production can also contribute to autoimmunity. These genetic changes can lead to the overproduction of inflammatory molecules, which increases the likelihood of chronic immune activation. [61]

It is important to emphasize that while these genetic variations raise the risk of autoimmune disease, they do not guarantee that the disease will develop. Environmental factors still play a crucial role in whether the condition is actually triggered.

Treating autoimmune diseases with functional medicine

A functional medicine approach that incorporates lifestyle-based strategies can help alleviate symptoms of autoimmune diseases and, in some cases, may even reverse the underlying autoimmune process.

1. Healing the gut

Healing the gut is a central element in treating autoimmune diseases. An anti-inflammatory diet that supports the growth of healthy gut bacteria is essential. In addition, probiotics may also be beneficial. Human clinical studies have shown that probiotics reduce the clinical severity of rheumatoid arthritis [62]. In people with multiple sclerosis (MS), probiotics have been shown to alleviate symptoms and improve quality of life. [63]

2. Maximum nutrient intake

Ensuring optimal intake of nutrients that support immune function can also reduce the symptoms of autoimmune diseases. Vitamin A, found in liver and egg yolks, positively influences the immune system and supports a healthy gut microbiota in people with autoimmune disease. Vitamin D, which is produced through sun exposure and found in fatty, cold-water fish, helps maintain the integrity of the gut barrier, thereby reducing intestinal permeability. Zinc, present in foods like meat and poultry, plays a key role in the maturation of both effector and regulatory T cells. Selenium has been shown to reduce thyroid peroxidase (TPO) antibodies in people with autoimmune thyroid disease [64–65]. Omega-3 fatty acids, including EPA and DHA, support inflammatory balance throughout the body. Glutathione, the body’s primary antioxidant, plays an important role in modulating innate immunity and helps protect against autoimmune disease.

3. Treating infections

Chronic infections—such as Lyme disease, Helicobacter pylori, and cytomegalovirus—are often overlooked, despite their significant role in triggering or sustaining autoimmune processes. Identifying and treating these infections with the help of a qualified healthcare provider may be essential for recovery and long-term disease management.

4. Minimizing stress

Psychological stress is a well-established contributor to autoimmune activity. Therefore, managing stress is an important part of any functional medicine treatment plan. There are many ways to reduce stress. Some people prefer physical activity, others benefit from breathing techniques or creative hobbies like painting or reading. The best method is personal, but one universal recommendation is meditation. Scientific research has demonstrated that meditation lowers stress levels and rewires the brain to respond more calmly and effectively to future challenges.

5. Regulate your circadian rhythm, get more sleep

Maintaining a healthy circadian rhythm is critical for supporting immune system function. To support your natural rhythm: Maintain a consistent sleep-wake schedule. Sleep in complete darkness. Avoid blue light exposure (such as screens) for at least one hour before bedtime, to preserve melatonin production.One additional strategy is time-restricted eating, which involves limiting food intake to a specific window of time each day—for example, between 8:00 a.m. and 6:00 p.m. Research suggests that this form of meal timing helps align the body’s circadian rhythms, which may lead to better overall health outcomes. [66]

Figure 5: Treatment of autoimmune disease with functional medicine

References

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[3] “Autoimmune Diseases” https://www.niehs.nih.gov/health/topics/conditions/autoimmune/index.cfm#footnote1

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