INTRODUCTION TO AUTOIMMUNITY AND THE GUT-BRAIN AXIS
Gut health is closely involved in autoimmunity (AI). In fact, there are three elements necessary for an autoimmune disease to develop. These are a genetic predisposition, a leaky gut and an environmental trigger (Fasano, 2012). This is commonly referred to as the triad of AI. Through intestinal permeability, or leaky gut, the gut becomes a critical factor in AI.
AI diseases are typically chronic and can require lifelong treatment. Conventional medicine says there is no cure for most AI diseases. But Functional Medicine has developed different approaches that can help to manage or improve an AI disease, and in some cases, to reverse an AI disease.
There are more than 100 different autoimmune diseases. Forty other additional diseases are thought to have an autoimmune component (The American Autoimmune Related Diseases Association, 2019). We cannot list them all here but common ones include multiple sclerosis, lupus, celiac disease, Crohn’s, Hashimoto’s, rheumatoid arthritis, fibromyalgia, type 1 diabetes, ulcerative colitis, vitiligo, Meniere’s disease and others.
AI diseases are becoming more and more common in our modern society.
- The National Institute of Health (NIH) estimates up to 23.5 million Americans suffer from autoimmune disease and that the prevalence is rising (The American Autoimmune Related Diseases Association, 2019). The NIH numbers only include 24 diseases for which good epidemiology studies were available (The American Autoimmune Related Diseases Association, 2019).
- The American Autoimmune Related Diseases Association (AARDA) says that 50 million Americans suffer from autoimmune disease when all AI diseases are included (The American Autoimmune Related Diseases Association, 2019).
- Autoimmune diseases are more common in women, and they often run in families.
AUTOIMMUNITY & GUT HEALTH
Autoimmunity (AI) occurs when the body’s immune system attacks itself. The immune system protects the body by responding to invading microorganisms, such as viruses or bacteria, by producing antibodies or other types of immune cells. Normally, an immune response cannot be triggered against the cells of one’s own body. In some cases, however, immune cells make a mistake and attack the cells that they are meant to protect. Essentially, the person’s immune system attacks its own tissue. This can lead to a variety of autoimmune diseases.
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WHAT FACTORS AFFECT GUT HEALTH?
Factors such as genetics, the environment, infections, and the gut microbiota all play a role in autoimmune disorders. The microbiome, meaning the specific bacteria in the gut, has a very important and long-term effect on the immune system, starting at birth. It also plays a significant role in autoimmune disease (Campbell, 2014).
It is not fully understood how the microbiome interacts with the immune system in either the development or the absence of an autoimmune condition (Thomas S, 2017). Microbial dysbiosis in early life can negatively affect how the immune system develops and provide the basis for allergic disorders or other health problems in later life (Thomas S, 2017). Dysbiosis may trigger intestinal permeability (or leaky gut) and consequently may trigger autoimmune diseases, given the right circumstances (Thomas S, 2017).
When leaky gut occurs, there are essentially small holes in the gut lining. Through these holes, various large protein molecules of undigested food can get into the bloodstream and travel all around the body. As this undigested food continues to pass through the holes of the gut lining, food intolerances will occur and the immune system will be triggered over and over into attacking these particles. Eventually, the immune system becomes excessively activated and goes into overdrive. Certain body tissue can look like undigested food molecules. This is called molecular mimicry.
The immune system can start to confuse a food or other foreign molecule with a particular body tissue, and start to attack its own tissue. This self-attack is what happens in an autoimmune disease. For example, Hashimoto’s is when the immune system attacks the thyroid. In MS, the attack is on the myelin sheath surrounding nerves.
WHAT CAUSES LEAKY GUT?
Several factors can lead to leaky gut:
DYSBIOSIS: Increased intestinal permeability is influenced by the make-up of the gut microbiota (Fasano, 2012). An unbalanced gut flora or dysbiosis, when more bad bacteria exist vs. good bacteria, can contribute to leaky gut. Dysbiosis has been associated with autoimmune diseases, particularly, rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS) and autoimmune liver disease (AILD) (Li, 2018).
ZONULIN: Zonulin is a protein that regulates intestinal permeability by modulating the tight junctions of the gut lining (Fasano, 2012). Zonulin has been found to be higher in autoimmune conditions associated with a dysfunction of the tight junctions, including celiac disease (CD) and T1D (Fasano, 2012). Both animal studies and human trials have established that zonulin is involved in the development of autoimmune diseases (Fasano, 2012).
Zonulin is triggered or increased by small intestinal exposure to bacteria, as in the case of SIBO or small intestinal bacterial overgrowth, and gluten (Fasano, 2012). These have been identified as the two more powerful triggers (Fasano, 2012) for higher zonulin, which will lead to leaky gut. In the small intestine, when exposed to excessive bacteria, zonulin is secreted in genetically susceptible individuals (Fasano, 2012). This affects the intestinal barrier function by releasing zonulin and can cause leaky gut (Fasano, 2012).
POOR DIET: Diet dramatically affects gut health and the specific strains of gut bacteria. The US diet has changed dramatically since the 1950’s. We have new strains of grains, especially in wheat, rice, soy, and corn. The food supply contains GMO’s, chemicals, pesticides, fungicides, insecticides, antibiotics, heavy metals, such as arsenic, chemical ingredients such as artificial preservatives, colorings, and flavorings and plasticizers such as bisphenol A. Animal products contain the hormones and antibiotics given to the animals. In addition, antibiotics, antacids, proton pump inhibitors, histamine 2 blockers, and other drugs are widely used.
In line with these dietary changes, there has been a significant increase in autoimmune diseases, linking the quality of diet and autoimmune problems (Campbell, 2014).
SPECIFIC DIETARY ELEMENTS THAT CONTRIBUTE TO LEAKY GUT:
- Refined and processed sugars
- Refined carbohydrates
- Genetically modified foods
- Vegetable oils
- Alcohol: Data indicate that alcohol is associated with dysbiotic changes in the gut microbiota, meaning that balance of good vs. bad bacteria tips into dysbiosis (Engen PA, 2015). Alcohol may also be associated with increased gastrointestinal tract inflammation and intestinal permeability resulting in systemic inflammation and tissue damage (Engen PA, 2015).
- Gluten: Gluten triggers the release of zonulin. Zonulin is a key factor in regulating tight junctions of the gut lining. Zonulin’s increase in genetically susceptible individuals may lead to immune-mediated diseases, i.e. autoimmunity (Fasano, Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications., 2012).
- Packaged, processed, and junk foods: Glucose, salt, emulsifiers, organic solvents, gluten and nanoparticles are increasingly used by the food industry, allegedly to improve the quality of food. All of these additives are known to increase intestinal permeability by breaking down the tight junctions of the gut lining (Lerner A, 2015).
- Any food to which a person has a sensitivity or allergy
STRESS: Stress is a factor and can disturb the make-up of the microbiome and increase permeability (Camilleri, 2019).
MEDICATIONS: Certain medications can increase intestinal permeability. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil), aspirin, Celebrex and others increase permeability (Camilleri, 2019). Other drugs, such as antibiotics and oral contraceptives disrupt the intestinal barrier (Bischoff SC, 2014).
Once a leaky gut is established in a genetically susceptible person, an AI disease may potentially develop.
CERTAIN, OFTEN PATHOLOGICAL, BACTERIAL STRAINS ARE FOUND IN DYSBIOSIS AND WITH CERTAIN AI CONDITIONS.
Dysbiosis should be identified, monitored and treated because it can contribute to autoimmunity. Most infectious agents, such as viruses, bacteria and parasites, can induce autoimmunity via different mechanisms (Kivity S, 2009). Bacterial infections in particular are associated with many autoimmune diseases involving chronic inflammation (Sherbet, 2009).
In many cases, it is not a single infection but rather the ‘burden of infections’ from childhood that is responsible for the development of autoimmunity. The development of an autoimmune disease after infection tends to occur in genetically susceptible individuals, often with intestinal permeability or gut dysbiosis (Kivity S, 2009).
• ENTEROCOCCUS GALLINARUM: One study has linked autoimmune reactions to a bacterium in the gut called Enterococcus gallinarum (Manfredo Vieira S, 2018). The autoimmune response can be triggered when the bacterium spontaneously migrates from the gut to other organs in the body, such as the spleen, liver, and lymph nodes (Manfredo Vieira S, 2018). The results were confirmed when researchers compared cultured liver cells of healthy people versus those of people with an autoimmune disease and found traces of Enterococcus gallinarum in the autoimmune group (Manfredo Vieira S, 2018).
• BACTEROIDES FRAGILIS: Another study has identified the bacteria Bacteroides fragilis to be involved in AI (Stewart L, 2018). A protein produced by this common gut bacteria may trigger the onset of autoimmune disease through the concept of molecular mimicry. Researchers found that patients with autoimmune disorders display higher-than-normal levels of a “mimic protein” produced by Bacteroides fragilis (Stewart L, 2018). This specific microbe in the gut produces protein molecules that mimic a human protein, which can cause the immune system to attack its own cells by mistake through molecular mimicry and this can contribute to autoimmunity (Stewart L, 2018).
• KLEBSIELLA PNEUMONIAE: It has been known for some time that the pathogenic bacteria, Klebsiella pneumoniae, is linked to certain AI diseases (Rashid T, 2013). Studies have found that Klebsiella is the most likely triggering factor involved in the initiation and development of two autoimmune diseases; ankylosing spondylitis (AS) and Crohn’s disease (CD) (Rashid T, 2013). It appears that Klebsiella microbes can grow and thrive in the bowel of genetically susceptible people.
• MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS or MAP: MAP is a bacterium that is the known infectious cause of Johne’s disease, a chronic inflammatory bowel disease (IBD) in cattle (Dow, 2012). MAP is also involved in Crohn’s disease, which is very similar to Johne’s. MAP acts as a trigger of autoimmune disease and is associated with autoimmune diabetes, autoimmune thyroiditis and multiple sclerosis (Dow, 2012).
• PREVOTELLA COPRI: In a study of 114 people, a bacterium named Prevotella copri was present in the gut of 75% of people with rheumatoid arthritis (RA) compared to only 21% of healthy control subjects (National Institutes of Health (NIH), 2013). In addition, an abundance of Prevotella copri has been identified in patients newly diagnosed with rheumatoid arthritis (Alpizar-Rodriguez D, 2019). The presence of P. copri corresponds to a reduced amount of other beneficial microbes (Scher JU, 2013). This indicates the role of intestinal dysbiosis in the development of RA (Alpizar-Rodriguez D, 2019).
• PROTEUS: A strong link exists between Proteus mirabilis microbes and RA (Ebringer A, 2006). It is thought that sub-clinical Proteus urinary tract infections are the main triggering factor (Ebringer A, 2006). In addition, molecular mimicry between these bacteria and the specific tissue under immune attack in RA leads to the continuation of the disease process (Ebringer A, 2006).
In short, pathogenic bacteria can be highly problematic to overall gut health. In certain people with a genetic disposition, they can contribute to the development of autoimmunity. This is why is extremely advisable to be mindful of your gut health and consistently work on supporting a healthy gut.
Please follow us again next week when we will continue with Autoimmunity & the Gut Part 2. We will discuss specific microbiome issues in common AI diseases and we will give you ways to manage and address an autoimmune condition.
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