Autoimmunity and the GI Microbiome
David M. Brady, ND, DC, CCN, DACBN, IFMCP, FACN
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).1The 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.
Figure 1:
Rise in Incidence of Immune Disorders in Latter Half of 20th
Century
The typical allopathic clinical approach to autoimmune disorders focuses on the management of symptoms with various anti-inflammatory medications and often the use of chemotherapeutics, and very potent immunosuppressive agents with nasty potential side-effects like leukemia and lymphoma.2 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 pathological process. However, modern research into autoimmune phenomenon suggest radically different approaches may be required to reverse the above cited trends, including a strong emphasis on very early detection with predictive autoantibodies, a focus on optimizing gastrointestinal mucosal immune function and the microbiome, eradication of infectious agent triggers with antimicrobial therapy, and even the seemingly bizarre use of parasitic agents therapeutically. Some of these concepts have a long history in naturopathic and functional models of medicine, but now are emerging as hot areas of emphasis in mainstream medical research journals and investigative communities in immunology.
Molecular Mimicry:
The concept of molecular mimicry is really a simple one, and it is an area attracting considerable research related to the genesis of autoimmune disorders. Simply stated, environmental exposure to specific antigens (including dietary peptides and those expressed by microbes), can in genetically susceptible individuals induce cross-reactions with structurally similar amino acid motifs associated with specific host tissues. There are now multitudes of associations that have been firmly established between immune incompatibility with specific dietary-derived antigens, as well as the overgrowth of certain opportunistic and pathogenic gastrointestinal bacteria, and the presence of specific autoimmune disorders (See table 1)3. While some of these associations have been known for quite some time, mechanisms of causality 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 Grave’s disease) who visit a rheumatologist or endocrinologist do not routinely have stool analysis of their GI microbiota or food sensitivity testing performed.
One of the most striking examples of molecular mimicry comes from the work of Alan Ebringer. He and his group in the United Kingdom have established over the course of many years that a substantial percentage of patients diagnosed with RA have chronic stealth infection with Proteus mirabilis in the upper urinary tract.4 His group has also established the specific amino acid motifs of cross-reaction between the Proteus hemolysin and the RA-associated HLA-DR molecules, as well as those between the Proteus urease enzyme and hyaline cartilage, containing type XI collagen, the type only found in the small joints affected in RA. His successful treatment protocol includes antibiotic therapy, such as ciprofloxacin (sometimes in combination with NSAIDs, DMARDS, and immunosuppressive agents as needed), with the added use of natural blocking agents such as cranberry juice, vitamin C for urine acidification, and plenty of fluids.5
While all these associations may be interesting to researchers, what does this really mean to a clinician? Some critics would argue that there is a lack of interventional data to suggest eradication of associated organisms and food antigens positively affects patient outcomes. This may be true in some instances, but it has been well established, for instance, by Ebringer that successful treatment of Proteus clinically helps those with RA,5 and dietary elimination of gluten-containing grains is entirely accepted as the most viable intervention in Celiac disease. One potential issue in play is that by the time a patient is diagnosed with autoimmune disease there is often already substantial host-tissue damage. Perhaps the 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 clinically. In the naturopathic and functional medicine models, there is a strong emphasis on both early detection and interventions that target the underlying pathophysiologic basis and underlying 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; 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 the interventions required pose little or no risk and are also relatively inexpensive, including probiotics, antimicrobial botanicals and volatile oils, mucosal-supporting nutrients and botanicals, and dietary modulation. Substantially improved molecular methods to assess the GI microbiota utilizing qPCR-DNA methodology, such as the GI-MAPTM test, are also now available to clinicians at relatively low cost with rapid turn-around time.6
Learn more about the functional medicine approach to autoimmune disease and many other chronic health conditions through Dr. Brady’s latest educational platform Functional Medicine & Nutrition Virtual Classroom with Dr. David Brady & Friends at OnlineCE.com/DrBrady.
Author Biography:
Dr. Brady has 30 years of experience as an integrative practitioner and over 25 years in health sciences academia. He is a licensed naturopathic medical physician in Connecticut and Vermont, is board certified in functional medicine and clinical nutrition, a fellow of the American College of Nutrition, and completed his initial clinical training as a Doctor of Chiropractic. Dr. Brady has been the chief medical officer of Designs for Health, Inc. for 17 years. He is also one of founders of Diagnostic Solutions Labs and serves as the chief medical officer for the lab. He was the long-time vice president for health sciences and is the director of the Human Nutrition Institute and associate professor of clinical sciences emeritus at the University of Bridgeport in Connecticut. He has appeared on the plenary speaking panel of some of the largest and most prestigious conferences in the field including IFM, ACAM, A4M, ACN, IHS, AANP, AIHM and many more. He is in clinical practice at Whole Body Medicine in Fairfield, CT, specializing in functional, nutritional and metabolic medicine. Dr. Brady has published a multitude of peer-reviewed scientific papers and textbooks related to chronic pain, autoimmunity and functional gastroenterology and is a featured contributing author in the medical textbooks; Advancing Medicine with Food and Nutrients-2nd Ed. (edited by Kohlstadt I-Johns Hopkins Univ.), Integrative Gastroenterology (edited by Mullin G-Johns Hopkins Hospital) and Laboratory Evaluations for Integrative and Functional Medicine -2nd Ed. (edited by Bralley & Lord). His latest popular book, The Fibro-Fix, was published by Rodale. His latest educational project is a learning transfer platform Functional Medicine & Nutrition Virtual Classroom with Dr. David Brady & Friends at OnlineCE.com/DrBrady
References:
1. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. Sep 2002;347(12):911-920.
2. Inaba M, Ushijim S, Hirata N, et al. Methotrexate-related lyphomatoid granulomatosis in a patient with rheumatoid arthritis. Nihon Kokyuki Gakkai Zasshi (Article in Japanese). Aug 2011;49(8):597-601.
3. Mayes MD. Epidemiologic studies of environmental agents and systemic autoimmune diseases. Environ Health Perspect 1999;107(suppl. 5):743-748
4. Ebringer A, Rahid T. Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol. Mar 2006;13(1):41-48.
5. Ebringer A, Rahid T, Wilson C. Rheumatoid arthritis: proposal for the use of anti-microbial therapy in early cases. Scand J Rheumatol. 2003;32:2-11.
6. Brady D, Nelson-Dooley C., Methodology Matters in Diagnostic Stool Analysis. Townsend Letter, January 2021.