Autoimmunity: What is the root cause and why is it on the rise?

Autoimmunity can be described as a condition that develops when the immune system mistakenly attacks healthy cells in the body. Autoimmunity can take on many different forms as it can affect any part of the body. For some, it results in hormone disruption, and for others, it can present as pain, fatigue, or even neurological changes. Despite a variety of clinical signs and symptoms, autoimmune diseases are a result of immune system changes that cause inflammation and damage.

What is most concerning with autoimmune disease is that the incidence rates are increasing worldwide by 4 to 7% every year. Notably, there has been the greatest increases in celiac disease, type 1 diabetes, and myasthenia gravis – a condition that causes rapid fatigue of the muscles. To date, according to The National Institutes of Health (NIH), up to 23.5 million Americans currently, suffer from one or more autoimmune disease and once you have one autoimmune disease you are more likely to develop another.

What Causes Autoimmune Disease?

The development of autoimmune disease is multifactorial meaning there is no singular cause. There are multiple variables linked to the onset of the condition including genetics, environmental toxins, stress and infectious causes. Some studies have shown that genetic predisposition accounts for only roughly 30% of all autoimmune diseases, leaving the remaining 70% as the result of environmental factors, like toxic chemicals, diet, infections, and gut dysbiosis. This is actually great news because it means that with early detection in combination with dietary and lifestyle changes we can identify, slow down, and even reverse autoimmune disease.

Foods & Toxic Chemicals Can Trigger Autoimmunity

Our immune system is filled with immune cells that stand guard defending our bodies against foreign materials like toxins and foods. A key class of immune cells are antigen presenting cells (APCs) which include macrophages and dendritic cells. These cells are triggered by foreign material and their job is to sound the alarm to the immune system that a suspicious particle has entered. This stimulates cytokines to be produced by the immune system and released into circulation. Anti-inflammatory cytokines are released to stimulate the T-regulatory cells to monitor the reaction while pro-inflammatory cytokines trigger inflammation and antibody production. The balance of two is critical and imbalances cause autoimmunity.

The T-regulatory cells are like the bouncers who have the power to intervene in the process and stop the inflammatory immune reaction by developing tolerance. This is why we can consume foreign foods or be exposed to environmental allergens and not mount an immune reaction. However, if T-reg cells do not step up then naive T cells will continue reacting and start to morph into TH1, TH17 and TFH cells. These immune cells can trigger autoimmune disease when the inflammation gets out of control, antibodies are produced and tissues are damaged. It is the breakdown of immunological tolerance that leads to autoimmune responses that we see in the development of autoimmune disease.

When the body is healthy the immune system is able to distinguish yes this cell is “me”. However, there are toxic chemicals in our environment that enter into tissues and form bonds with healthy cells. This changes the structure and makes them unrecognizable to the immune system. This is where T cells bind to the cell they now don’t recognize and call over their B cell friends to make antibodies beginning the attack on its own healthy tissues.

Literature exists showing that toxic chemicals and foods that can trigger autoimmune disease yet little is done to prevent human exposure. Some of the chemicals include bisphenol A (BPA), mercury, asbestos, mycotoxins, trichloroethylene (TCE), benzoquinones, formaldehyde, ethylene oxide, penicillins, cigarette smoke, nail polish, sodium (salt), gluten, dairy, and glyphosate (1). While it is unlikely that one exposure will cause autoimmunity, with the genetic predisposition and multiple daily exposures one can see how the risk of autoimmune disease is elevated.

Here are some examples of toxins and their relationship to autoimmunity.

• Nail polish contains halogenated compounds that can bind to mitochondrial proteins, changing their immunogenicity and inducing anti-mitochondrial antibodies (2).
• Cigarette smoke and alcohol consumption are capable of modifying DNA methylation which results in changes in gene expression (3).
• An excess uptake of salt can affect the innate immune system by interfering with macrophage function through TH-17 cells (4,10).
• Drinking cow’s milk may induce autoimmunity due to cross-reactivity of its albumin component with islet cell antigen-1 and beta cell surface protein (5).
• A wheat-based diet induces not only TH1-type cytokine bias in the gut but also increased T-cell reactivity to gluten, with a higher frequency of diabetes (6).
• Gluten increases zonulin levels (a marker of leaky gut) and the upregulation of genetically susceptible individuals may lead to autoimmune disease (7).
• Glyphosate exposure has been linked to a non-exhaustive list of possible diseases which include autism, multiple sclerosis, type 1 diabetes, coeliac disease, inflammatory bowel disease and neuromyelitis optical (8,9)

Microbes That Are Associated with Autoimmune Disease

Like toxic chemicals and foods, pathogens also have the ability to trigger autoimmune disease. Pathogenic infections, meaning microbes that have the ability to cause disease, are thought to stimulate autoimmune disease in four different ways: molecular mimicry, epitope spreading, dysregulation of immune homeostasis, and the bystander effect.

Molecular mimicry: Every cell in our body contains proteins that the immune system looks at to determine if this is self vs non-self. Invading organisms are able to evade detection through molecular camouflage. Certain pathogens can develop epitopes of themselves that look exactly like epitopes of healthy human tissues which allows the pathogen to avoid immune detection and start to multiply within the cells. The issue is if the immune system does recognize the pathogen and starts to produce antibodies those same antibodies will also damage self-tissue because of the close resemblance.

Epitope spreading: Some pathogens are able to get into healthy cells and hijack the cell’s machinery such that it produces proteins that favor the virus or bacteria. Eventually, these proteins force the cell to burst open and release the now multiple pathogens and their weapons throughout the body.

Immune dysregulation: This occurs when the immune system shifts and remains in an inflammatory phase that breeds autoimmune disease. When the body is healthy the T-reg cells (the referees) should shift the immune system from the inflammatory phase into an adaptive phase, where it begins to develop tolerance. Being forced to remain in the pro-inflammatory state is a breeding ground for autoimmune disease.

The bystander effect: When a virus, fungi, parasite or bacteria infect healthy tissue, collateral damage is done to healthy non-infected cells surrounding the area. This is because inflammation signals an influx of immune cells like natural killer cells to take care of the invaders. The immune system does a great job at attacking infected tissue but they are sloppy and often damage surrounding tissue. When healthy tissue is damaged there can be miscommunication and continued attack on healthy tissues.

Pathogenic infections have been associated with a vast number of autoimmune diseases (7-8). This table depicts some of the more common pathogen-associated autoimmune diseases.

Microbial Diversity & Gut Dysbiosis

The gut microbiome needs to include a variety of healthy bacteria in order to thrive. Research shows that low microbial diversity in the gut is also associated with increased risk for autoimmune disease and increased incidence of infection (9). A 2015 study showed that just one week of broad-spectrum antibiotics, can negatively impact the gut microbiome, decreasing the microbial diversity for up to a years after the medications have left the system (15). This study concluded that “clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome”.

The key to restoring gut biodiversity to to support the beneficial bacteria that reside in the gut, like Bacterioides fragilis, Faecalibacterium prausnitzii, Akkermansia muciniphila, Bacillus spores, and non-infectious Clostridia spp, can all help protect against autoimmune disease through the up-regulation of the T-reg system, suppression of TH-17, restoration of the intestinal mucus layer, and the reduction of systemic inflammation (10). In this way, reconditioning the gut microbiome can help prevent and correct autoimmune responses within the body.

Summary

In summary, autoimmune disease develops from multiple triggers. Often a genetic predisposition exists but many modifiable environmental triggers lead to the development and progression on autoimmunity. Ways to intervene and reduce the risk of autoimmunity include reducing toxic chemical exposure, dietary interventions as well as removing pathogenic infections and supporting a healthy gut microbiome.

Environmental health solutions:

• Dramatically reduce sodium intake
• Grow your own food when possible to minimize glyphosate exposure
• Consume prebiotic fibers
• Use natural household cleaners when possible
• Avoid skincare or cosmetics that aren’t safe for human consumption
• Avoid Dairy
• Limit or avoid antibiotic use unless absolutely necessary
• Avoid gluten and crops that use glyphosate for desiccation (corn, potatoes, barley, oats, etc)

Gut health solutions:

• Eat a variety of fruit and vegetables to promote biodiversity in the gut
• Take Bacillus spores to help repair leaky gut and improve microbial diversity
• Avoid prolonged antimicrobial use when possible
• Keep fat intake below 30% of daily caloric intake to up-regulate the T-reg system and reduce the Firmicutes/Bacteroidetes ratio.
• Fast 14-16 hours daily (intermittent fasting) to promote increases in Akkermansia muciniphila (17).
• Consume prebiotic fibers like xylooligosaccharies (XOS), fructooligosaccharides (FOS), and galactoligosaccharides (GOS) that feed only beneficial bacteria to improve microbial diversity. Kiwi contains these prebiotic fibers but you must consume the entire Kiwi.
• Supplement with gut healing herbs, IgG powder, L-glutamine, and nutrients like  L-proline, L-serine, L-threonine and L-cysteine to repair leaky gut (16).

References

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15. Zaura, Egija, et al. “Same exposure but two radically different responses to antibiotics: resilience of the salivary microbiome versus long-term microbial shifts in feces.” MBio 6.6 (2015): e01693-15.
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