Autoimmune Disease: A Modern Epidemic?
There is simply no doubt that the incidence of autoimmune disorders has been rising sharply over the past several decades in the Western industrialized countries, particularly the United States (See figure 1). The question is why has there been such a sharp rise in the incidence of these disorders? The answers may very well be found in the current medical research, but you would probably never know it by visiting a doctor. This may be because this situation serves as an example of the giant chasm that often exists between Western medical research, which is often outstanding, and the practice of clinical medicine, which often leaves quite a bit to be desired when it comes to the management of chronic complex disorders with high morbidity (disability) but low mortality (death) rates.
The typical conventional medical approach to autoimmune disorders focuses on the management of symptoms with various anti-inflammatory medications and often ultimately the use of chemotherapeutic drugs and very potent immunosuppressive agents with nasty potential side-effects like leukemia and lymphoma. While these approaches admittedly can provide substantial symptomatic relief to the patient, they do not really get to the cause of these conditions and some research suggests that these approaches may result in a furthering of the underlying disease process. However, modern research into autoimmune diseases suggest radically different approaches may be required to reverse the above cited trends, including a strong emphasis on very early detection with predictive auto-antibody testing, a focus on optimizing the gastrointestinal health/environment (i.e., the microbiome), including the eradication of infectious immune triggers with antimicrobial therapy, and even the seemingly bizarre use of helminth parasites (worms) as therapy. Some of these concepts have a long history in naturopathic, integrative and functional models of medicine, but now are emerging as hot areas of interest in mainstream medical research journals and investigative communities in immunology.
The concept of molecular mimicry is really a simple one, and it is an area attracting considerable research related to why autoimmune disorders occur. Simply stated, environmental exposure to specific antigens (immune system-triggering proteins in food and on microbes like viruses and gut bacteria) can, in genetically susceptible individuals, induce a cross-reaction with structurally similar proteins associated with specific body tissues. In other words, something from the outside, such as a food or bacteria, that you may be genetically susceptible to over-reacting to, may trigger an immune reaction to also occur against part of your own body.
There are now multitudes of associations that have been firmly established between immune incompatibility with specific food-derived proteins, as well as the overgrowth of certain gastrointestinal bacteria, and the presence of specific autoimmune disorders (See table 1). While some of these associations have been known for quite some time, mechanisms of causality (pathways in which an associated triggering antigen can cause autoimmune activity against a specific body tissue or structure) are rapidly being established in the research. However, patients suffering from disorders like rheumatoid arthritis (RA), ankylosing spondylitis (AS), and autoimmune thyroiditis (i.e., Hashimoto’s or Graves’ disease), multiple sclerosis (MS), lupus (SLE), etc., who visit a rheumatologist or endocrinologist do not routinely have stool analysis to assess their GI microbiota or food sensitivity testing to detect these potential triggers. This is ironic, particularly in the case of bacterial overgrowth in the gut, as the conventional medical paradigm typically assumes an infectious cause until proven otherwise. Perhaps this is just another example of resistance to significant change in clinical approach within medicine, even in the face of compelling evidence to do so, as it would then require a least a passive admission that something so seemingly simple was missed for so long.
For example, oral bacterial infection with Porphyromonas gingivalis, the primary bacterial cause of periodontal (gum) disease, may also play a role in the direct development of some cases of rheumatoid arthritis (RA). Many other researchers have now also gone beyond establishing mere associations between the presence of various microbes and autoimmune disorders. Some have actually experimentally induced autoimmune disease in animals by introducing specific bacteria into their gut, and have then resolved it by introducing another, making a compelling argument for a causal relationship between the imbalances in the GI microbiota and autoimmune activity.
Food proteins have also been linked to autoimmune diseases like Hashimoto’s and Graves’ diseases of the thyroid. Celiac patients (those with a severe intolerance to gluten-containing grains) have approximately 10 times the rate of auto-immune thyroid diseases as non-celiac individuals. It may be no coincidence that the emergence of an apparent epidemic of autoimmune diseases has corresponded with the ever-increasing consumption of poor-quality modern processed foods known to both negatively alter the GI microbiome and to contain a constant (often hidden) stream of offending dietary antigens, including gluten-containing grains and genetically modified proteins (GMO foods).
While all of these associations may be interesting to researchers, what does this really mean to doctors and their patients? Some critics would argue that there is a lack of interventional data to suggest that eradication of these associated organisms and/or avoidance of these dietary antigens positively affects patient outcomes. This may be true in some instances, but it has been well established in others. Dietary elimination of gluten-containing grains is entirely accepted as the most viable intervention in Celiac disease, an autoimmune disease of the intestinal tract.
One potential issue in play is that by the time a patient is diagnosed with autoimmune disease they are very far down the disease spectrum and there is often already substantial tissue damage. The proverbial horse has already left the barn. However, what if potential triggers were routinely screened for and removed by health care providers, particularly in those with a family history of autoimmune disorders? The entire course of the disorder might be favorably altered, and many of these disorders might potentially never emerge if the correct preventive measures were taken.
In the naturopathic, integrative and functional medicine models, there is a strong emphasis on both early detection and interventions that target the underlying basis and dysfunction of a disease process. Therefore, in these models the goal is to take clinical actions to reduce the potential for the disease process to progress. This also seems to intuitively make sense even in those who already have established disease, as even though you may not be able to undo the damage already done, you can likely – if nothing else- slow down the train. This is particularly true since these interventions pose little or no risk and are also relatively inexpensive; including dietary changes, the use of probiotics, antimicrobial herbals/botanicals and volatile oils to address GI bacterial overgrowth and to support the gut lining (to reduce “leaky-gut” syndrome).
The Hygiene Hypothesis
The concept of the hygiene hypothesis is also one that is quite simple, with the complexity being in the details. The thought that we have induced dysregulation into our immune systems by virtue of living in too clean of an environment, coupled with the over eradication of infection, is not new (See figure 1), but it has gained favor with researchers who have begun to work out exactly why this may be the case. Some of these concepts were elegantly addressed by Weiss in an editorial in the New England Journal of Medicine entitled Eat Dirt-The Hygiene Hypothesis and Allergic Disease.
There is no doubt that modern public health measures, such as adequate sewage systems, water treatment, the use of antibiotics, and various other aspects of modern hygiene have lessened deadly infectious outbreaks and have prevented unnecessary deaths. However, as with most things, there is a yin and yang. This new “clean world” has likely resulted in a lack of adequate sampling of our environment, including a lack of exposure to all of the microbes that we share our planet with, particularly while we are young and our immune systems are developing the delicate balance between adequate defense and tolerance of our surroundings.
In a 2010 paper in Nature Reviews-Immunology entitled Farm Living-Effects of Childhood Asthma and Allerg,y authors Mutius and Vercelli state: “Numerous epidemiological studies have shown that children who grow up on traditional farms are protected from asthma, hay fever and allergic sensitization. Early-life contact with livestock and consumption of unprocessed cow’s milk have been identified as the most protective exposures.”
Does this mean that our children who are: 1) growing up in more urban and suburban environments; 2) living in comparatively sterile homes; 3) drinking chlorinated water; 4) being bathed and scrubbed daily with anti-bacterial soap; 5) not being allowed to play in the dirt; 6) being given antibiotics every time they have a sniffle… are actually being harmed from an immunologic perspective and will carry this dysfunction with them throughout their entire lives? This is likely the case, and one of the reasons why, as parents of two young boys, my wife and I constantly try and balance the need for cleanliness with allowing them to be children and dig in the dirt, play in the stream in our backyard, and otherwise sample their living environment.
The Role of Parasites
As reported by David Gutierrez in NaturalNews, researchers in a study conducted at the University of Nottingham, point out that humans and gastrointestinal parasites might have co-evolved in a way that the parasites actually help regulate the human immune system to prevent allergies. They believe that over the course of millions of years, gastrointestinal parasites, such as various worms (helminths) have evolved the ability to suppress the human immune system as a survival mechanism. Because parasitic infestation has been so common throughout human evolutionary history, the human immune system has in turn evolved to compensate for this effect. This means that if the parasites are rapidly removed from the population (as has happened with modern hygiene, water treatment and the use of antimicrobial drugs), the immune system may then actually function too strongly, resulting in maladaptive immune responses such as asthma, allergies, and eczema. To test this concept the researchers studied over 1,500 children in rural villages in Vietnam where parasitic infestation with hookworm is still extremely common and allergies are not. Medical eradication of parasitic infection resulted in skyrocketing incidence of allergy, including dust mite sensitivity, supporting the hypothesis that parasites were favorably modulating their immune response.
With issues such as the hygiene hypothesis, and the role of parasites in immune function in mind, gastroenterologist and researcher Dr. Joel Weinstock, originally at the University of Iowa, and now Tufts University, has performed novel work with subjects with the autoimmune disorder inflammatory bowel disease (IBD). IBD was unheard of before the 20th century. Beginning of 20th century incidence is thought to be about 1:10,000 and is now 1:250.
Similar data exists with the incidences of asthma, hay fever, diabetes, multiple sclerosis, etc. Weinstock conducted various studies of IBD patients and treated them with the therapeutic parasite Trichuris suis, a pig whipworm, which was an ideal choice as it only remains viable in the human GI tract for a short time and must be continually administered. The organism, when introduced into patients with IBD, generally produced a balancing of the immune response and a lessening of symptoms and severity of disease. Pharmaceutical agents are now being developed along these lines to treat IBD.
Intestinal Hyper-permeability (aka: “Leaky Gut Syndrome”)
Leaky gut syndrome for much of the past twenty years seemed something that just naturopathic and functional medicine doctors talked about. Not any longer! Prestigious researchers such as Dr. Alessio Fasano at Harvard University, have been researching the role of intestinal permeability as part of the cause of autoimmune disorders and bringing this concept full-speed to the conventional medical research community through his publications in top-tier immunology and gastroenterology journals. In a 2009 article in Scientific American he eloquently brought the topic to the lay audience with his article Surprises from Celiac Disease, where he described that his theory that leaky gut contributes to Celiac disease and autoimmunity and it was initially greeted with skepticism by his colleagues.
Fasano has proposed that in order for autoimmune disease to manifest there must be three factors present, and he equates these to a triangle, or three-legged stool, where if any are not present the disease cannot exist. These three factors include; 1) an environmental trigger (i.e., food, bacterial, or viral protein/antigen), 2) a genetic susceptibility of the individual, and 3) intestinal hyper-permeability (i.e., “leaky gut syndrome”). He goes on to opine that by far the easiest of these three factors to treat is intestinal permeability. Much of his work involves the study of a protein which alters intestinal permeability by the name of zonulin. His team has a potential drug in development to alter the effect of zonulin to treat leaky gut.
Functional medicine and naturopathic physicians, and other nutritionally-minded providers, have been addressing the issue of leaky gut for a long time with effective natural agents, including; L-glutamine, N-acetyl-glucosamine, various anti-inflammatory herbals/botanicals and bioflavonoids, zinc-carnosine, omega-3-fatty acids and more with much success.
Predictive Autoantibody Testing (A True Application Preventive Medicine?)
In a 2007 Scientific American article entitled New Predictors of Disease, Abner Louis Notkins stated, “Molecules called predictive autoantibodies appear in blood years before people show symptoms of various disorders. Tests that detect these molecules could warn of the need to take preventive action.” Some of these tests have been used for many years simply to confirm the presence of a disease strongly suspected by a doctor once the patient has obvious signs of a particular autoimmune disease. However, the development and availability of low-cost autoantibody testing has ushered in the possibility to use these in a much more proactive screening strategy to predict the future emergence of autoimmune disorders so that preventive action can be initiated early to short-circuit the disease process.
It is hoped that this article will help the patient, and their doctor, to develop a comprehensive conceptual framework from which to view autoimmune disease and to institute a new proactive model from which to approach these challenging and ever-increasing disorders. Physicians should look for autoimmune conditions with a strong emphasis on: 1) very early detection with predictive auto-antibodies; 2) a focus on optimizing gastrointestinal immune function and the microbiome; 3) the eradication of infectious triggers with antimicrobial therapy, when appropriate; 4) the detection and elimination of food sensitivities; 5) allowing our children to gain more exposures through early contact with their environment; and 6) the promotion of an anti-inflammatory and healthy diet and lifestyle.
Dr. David M. Brady is a Connecticut and Vermont licensed naturopathic medical physician and certified clinical nutritionist. He is the vice president of the Division of Health Sciences, director of the Human Nutrition Institute, and associate professor of clinical sciences at the University of Bridgeport. He is also the chief medical officer for Designs for Health, Inc. and Diagnostic Solutions Labs, LLC, and practices at Whole Body Medicine in Fairfield, CT, specializing in functional and nutritional medicine. His latest popular book, The Fibro-Fix, was published by Rodale and released July of 2016 and coincided with his hosting of the popular online Fibro-Fix Summit in June of 2016 with over 30,000 attendees. You can learn more at: DrDavidBrady.com, FibroFix.com.