Image of Alcatraz Island. Type I diabetes is caused by autoimmune destruction of Islet (Island) cells of the pancreas. Clinicians are unsure why good immune cells turn bad, and why autoimmune diseases (the second leading cause of disability in the U.S.) are becoming more common. (Photo via Dhilung Kirat)
The American Diabetes Association recently revealed that the incidence of Type I diabetes is on the rise among American children. Unlike Type II diabetes which is impacted by lifestyle habits (exercise and dieting can often thwart Type II diabetes), Type I diabetes is an autoimmune disease resulting from an abnormally-functioning immune system (there are no known interventions to thwart Type I diabetes). The reasons for the increase in incidence[i] of Type 1 diabetes are unknown.
The rates of other autoimmune diseases are increasing as well. For example, the incidence of systemic lupus erythematous (SLE or lupus) tripled over a recent 50 year span. Researchers also inferred that the rates of ulcerative colitis and Crohn’s disease, two forms of inflammatory bowel syndrome (IBD), are increasing. Today autoimmune diseases are the 2nd leading cause of chronic illness and disability in the U.S., and the top cause of chronic illness in women (women are three times more likely to get an autoimmune disease compared to men).
Unfortunately, many autoimmune diseases go unrecognized by healthcare providers. The American Autoimmune Related Diseases Association (AARDA), a nonprofit organization “dedicated to the eradication of autoimmune diseases,” reports that the average autoimmune disease sufferer sees 6 doctors and spends up to 4 years before receiving a correct diagnosis.
Understanding AutoImmune Diseases
Autoimmune diseases are diseases that result from the body’s immune system attacking its own cells and tissues.[ii] Common symptoms associated with autoimmune diseases include general fatigue, dizziness, and low-grade fever. Other symptoms are typically more specific to the tissues and organs being targeted by the immune system. Overall there are 80 to 100 identified autoimmune diseases, and some of the more common ones include lupus (SLE), scleroderma, rheumatoid arthritis, multiple sclerosis (MS), inflammatory bowel disease (IBD), Sjorgen’s disease, and Type 1 diabetes. Autoimmune diseases tend to be chronic and even life-threatening.
The cause of autoimmune diseases is unknown. Undoubtedly genes play a role:
"Autoimmune diseases tend to occur in families. If there's one case of autoimmune disease in the family, there's likely to be another case. However, it is not a particular autoimmune disease; it is generally a tendency to autoimmunity. One family member may have lupus, another family member may have Sjogren's disease, a third member of the family may have rheumatoid arthritis.” Dr. Noel R. Rose, Director of Johns Hopkins Center for Autoimmune Disease Research
However, genes alone do not cause autoimmune disease. Rheumatologist and researcher Dr. Esther Sternberg elaborates:
"In any complex disease, the tendency to develop inflammation comes from genes, but whether it's arthritis, multiple sclerosis or something else depends on such environmental factors as bacteria, viruses, chemicals or foreign proteins….In addition, there is a 'dose effect' of genes--if you inherit many autoimmune genes, you will be more likely to get an autoimmune disease, regardless of environmental exposures. If you inherit very few, then environmental factors--from chemical exposure to major stress--become more important." Dr. Sternberg notes, "The genes load the gun and the environment pulls the trigger.
Although the precise etiology for increasing rates of autoimmune diseases are unknown, researchers and clinicians frequently cite two theories: toxins in our environment, and something known as the “hygiene hypothesis.”[iii]
Interestingly, perhaps the strongest evidence for a toxic cause of autoimmune diseases comes from pharmaceutical drug studies. Two drugs, procainamide (a treatment for abnormal heart rhythms) and hydralazine (a treatment for high blood pressure) can induce lupus (SLE). When these drugs are discontinued, the lupus goes away. Additionally, gluten has been linked to celiac’s disease, the compound silica to scleroderma, and iodine is suspected to worsen autoimmune thyroid disease.
"Exposures from our environment are a significant contributor to today's rising rates," says Douglas Kerr, director of the Johns Hopkins states. Many physicians concur.
Researchers looking back at 300,000 death certificates from 26 states noted that people in certain occupations were more likely to die from autoimmune diseases. Farmers, nurses, teachers, textile machine operators, mining machine operators, and painters were more likely to die from autoimmune diseases. The study suggests that occupations with exposure to chemicals, animals, or in some cases the public, may be at an increased risk for autoimmune diseases.
Unfortunately, however, with the exception of the few noted compounds above, specific agents that increase the incidence of autoimmunity are still unknown. Dr. Rose notes
"We need more data associating autoimmune illness with specific exposures. And we also need plausible biological mechanisms to explain how those exposures produce or exacerbate disease. This will dominate our research agenda over the course of the next decade."
The “hygiene hypothesis” proposes that a lack of exposure to microbes in early childhood causes the immune system to develop incorrectly, leading to autoimmunity (and possibly also allergies and excess inflammation). Proponents of this “hygiene hypothesis” note that children growing up in western, industrialized nations have higher rates of autoimmunity, and may be exposed to fewer microbes due to more widespread use of antiseptics (antibiotics, antibacterials, etc).
The hygiene hypothesis is supported by several pieces of epidemiological data showing positive correlations between socio-economic level and autoimmune disease incidence:
- There is a positive correlation between gross national product (GNP) and incidences of type 1 diabetes and MS in Europe (http://www.nejm.org/doi/full/10.1056/NEJMra020100)
- Studies have shown that immigrants coming to the industrialized world from the developing world develop immunological disorders like autoimmunity diseases at greater rates the longer they live in the industrialized country (This is likely not genetic, as subsequent children of immigrants develop autoimmune disease at the same rate as citizens of the developed nation; http://onlinelibrary.wiley.com/doi/10.1002/ppul.10323/abstract)
- The prevalence of lupus (SLE) in African-Americans is much higher than in West Africans. (http://lup.sagepub.com/content/4/3/176)
The above data suggest that poorer hygiene (or increased exposure to microbes) correlates with decreased incidence of autoimmune disease. However, this does not prove that microbes are responsible for increased incidence of autoimmune disease.
First, one could reasonably question whether children of industrialized nations are exposed to less microbes. More plausibly however, one can argue that children of industrialized nations are exposed to more toxins. Therefore, toxin exposure, and not a lack of microbe exposure, may be responsible for increased incidence of autoimmune disease. Finally, differences in other factors such as diet and medical care could also impact incidence of autoimmunity in different nations.
Below are several interesting studies attempted to find a more direct relationship between microbes and autoimmune disease:
Researchers at Brigham and Women’s Hospital in Boston found that “germ-free mice” had excessive inflammation of the colon and lungs resembling asthma and colitis (as in "ulcerative colitis). Furthermore, these researchers found that exposing germ-free mice to microbes during their first weeks of life prevented the onset of these changes. Therefore, this study suggests that exposure to germs are beneficial in preventing against autoimmunity in the lungs and colon.
Interestingly however, a couple of recent studies appear to contradict the “hygiene hypothesis.”
Researchers studying multiple sclerosis (MS) recently discovered that gut bacteria may be linked to multiple sclerosis. MS is an autoimmune disease in which the immune system attacks nerves in the brain and spinal cord causing a wide array of symptoms.[iv] Researchers bred mice with mutations predisposing to MS and noted that these mice do not get MS when raised “germ-free.” However, when these germ-free mice were seeded with intestinal bacteria, about 80% developed MS-like symptoms whereas none of the germ-free mice did. The researchers hypothesize that MS may be triggered in individuals with a genetic predisposition to autoimmune disorders exposed to certain bacteria.
Similarly, researchers in Germany recently concluded that gut (intestinal) bacteria may trigger diseases like rheumatoid arthritis. The researchers bred mice genetically susceptible to rheumatoid arthritis (RA) and introduced them to different strains of gut (or intestinal) bacteria and noted different rates of developing RA. They concluded that gut bacteria may play an important role in developing rheumatoid arthritis and other autoimmune diseases like type I diabetes and multiple sclerosis (MS). Specifically, the researchers believe autoimmune disorders may actually begin as an immune system attack on gut bacteria that have penetrated our intestinal walls.
Putting it all together:
The first study mentioned above reinforces the hygeine hypothesis (noting that exposure to germs are beneficial in preventing autoimmunity).
But how can we explain the seemingly contradictory last two studies in which introduced bacteria were believed to trigger the autoimmune diseases MS and rheumatoid arthritis?
First, all three of the studies were completed in mice which reduces the relevance to humans.
Second, bacteria residing in the gut may have a different impact locally (ie on our small intestine and colon) than they do upon more distant parts of the body (ie in our joints, in our brain). Therefore, it’s possible that bacterial species introduced into the gut could prevent inflammatory / autoimmune reactions in the gut (ie the colon) yet still trigger autoimmune reactions at more distant part of the body (ie in joints and in the brain).
Third, perhaps not all microbes are created equal. Recently researchers identified most of the thousands of microbes living in and on us. Over time, I imagine researchers will identify not only additional virulent strains of bacteria and other microbes, but also virulent genes associated with these microbes.[v]
Finally, perhaps our microbiomes are like a garden with numerous plants and flowers. As long as no single plant or flower grows disproportionately, a healthy ecosystem is maintained (and as long as a healthy ecosystem is maintained, no plant or flower grows disproportionately). But if an insult like an herbicide is introduced into the garden that selectively kills the plants, the flowers will begin thriving (unopposed by the plants). And perhaps the pollen from the flourishing flowers will begin aggravating your allergies, and the once beautiful garden will become noxious.
Imagine this garden as our microbiomes, and the plants and flowers like different species of microbes. As long as all microbes grow in healthy proportion to one another, all is well. However, if an insult like an antibiotic is introduced, certain microbes will perish while others will flourish causing illness and autoimmunity (and perhaps even “desirable” microbes, like the desirable flowers, will become noxious).
What do you think?
- Why do you think the rates of autoimmune disorders like Type 1 diabetes, lupus, and inflammatory bowel disease (IBD) are increasing?
- Do you think environmental toxins or microbes play a greater role in autoimmunity?
- Additional articles on "Medicine" and "Microbes" (I particularly recommend "Human Bacteria Mapped...")
- You might be interested in Donna Jackson's book "The AutoImmune Epdemic" Ms. Jackson suffers from the debilitating autoimmune disease Guillen-Barre syndrome. Her article "Diseases Like Mine are a Growing Hazard" is excellent.
- Excellent article on the 2011 Nobel Prizer winners in Medicine awarded for 3 researchers' insight into the immune system. Very interesting and informative- it provides an overview of recent research into the immune system.
If you have autoimmune disease or have not yet received a diagnosis, consider:
- Women's Health on autoimmune disease, from the U.S. Dept. of Health- good overview of autoimmune disease. The site also included an extensive list of autoimmune diseases and related symptoms.
- Question and Answers on autoimmune disease from the American Autoimmune Related Disease Association, a nonprofit advocating for those suffering from autoimmune disease.
- Article on receiving a second opinion if you suspect you have an autoimmune disease or aren't sure. Diagnosis can be a long, arduous process spanning more than one specialist. Proactivity is encouraged.
[i]The “incidence” of a disease is the rate at which the disease appears. Specifically, incidence is the number of new cases that occur each year per 100,000 people.
[ii] “Auto” means “self,” and autoimmunity is when the immune system turns against its own body. Typically the immune system defends against harmful organisms like bacteria, viruses, and parasites. When a healthy person is infected with these organisms, our body’s immune system mounts an immune response, attacking the harmful invaders. Usually our immune system does an excellent job distinguishing between harmful invaders (which get attacked) and our own cells, tissues, and organs (which are not attacked). However, in autoimmune diseases, the body’s immune system inexplicably attacks our own cells, tissues, and organs.
[iii] Note that increased recognition and diagnosis of autoimmune disease may play a role in the increased incidence. However, this alone does not account for the increased incidence. Consider the following from Dr. Rose, “Given that type 1 diabetes has been well characterized for decades, this offers compelling evidence to date that rising incidence is not simply an illusion based on better diagnosis.”
[iv] Scleroses are lesions or scars. Multiple Sclerosis (MS) refers to the multiple lesions or scars that form in the brain and on the spinal cord.
[v] Bacteria for example can readily transfer genes and genetic material between one another in a process called conjugation.