After posting this morning about “winding down,” I ended up wanting to add a sub-section to the Autoimmune Diseases section in Chapter 8 of the book: The Gut Microbiome In Disease Pathology (html version). Thanks to Tim Steele for his major contributions to this as well. Hopefully you’ll see that the intended style is layman accessible, but well referenced for the geeks. Didn’t take the time to make it pretty for the blog (the link above has footnote links and links to citations), so here’s just a plain text:
A well established aspect of the gut microbiome is its close relationship with host immunity, essentially comprising 70% of the immune system. It’s no longer mere speculation that the composition of our gut microbes have a profound effect on the creation, training, maintenance, and actions of our immune system. An imbalance of intestinal microbes can cause an imbalance in our immune system, leading it to attack us instead of the pathogens it’s supposed to eradicate or keep in check. Here’s a partial list of autoimmune conditions that have been linked to disruptions in gut microbes:
* Addison’s Disease
* Ankylosing Spondylitis
* Antiphospholipid Syndrome (APS)
* Autoimmune Hepatitis
* Behcet’s Disease
* Bullous Pemphigoid
* Castleman’s Disease
* Celiac Disease
* Chronic Fatigue Syndrome
* Chronic Inflammatory Demyelinating Neuropathy (CIDP)
* Churg Strauss Syndrome
* Crohn’s Disease
* Giant Cell Arteritis
* Glomerulonephritis (Autoimmune Kidney Disease)
* Graves’ Disease
* Guillain-Barre Syndrome
* Hashimoto’s Thyroiditis
* Idiopathic Pulmonary Fibrosis
* IgA Nephropathy
* Interstitial Cystitis
* Kawasaki Disease
* Lichen Planus
* Meniere’s Disease
* Mixed Connective Tissue Disease (MCTD)
* Multiple Sclerosis
* Myasthenia Gravis
* Pernicious Anemia
* Polyarteritis Nodosa
* Primary Biliary Cirrhosis
* Raynaud’s Disease
* Reiter’s Syndrome
* Rheumatoid Arthritis
* Scleroderma or CREST Syndrome
* Silicone Immune Toxicity Syndrome
* Sjogren’s Syndrome
* Stiff-Man Syndrome
* Type 1 Diabetes
* Ulcerative Colitis
* Vascular Dementia
* Wegener’s Granulomatosis
Those with one or more of these autoimmune conditions are likely to have a diet high in modern, industrial Frankenfoods or one lacking in sufficient fibers our gut bugs recognize as food—but most likely both. The immune system keeps the body healthy by providing a fine balance between attacking invaders and maintaining healthy tissues. In autoimmune diseases, this delicate balance fails and the immune system attacks healthy tissue.
Let’s take a brief look at a few autoimmune conditions positively identified with altered gut microbes.
Rheumatoid Arthritis –
In rheumatoid arthritis, the immune system attacks membranes that line the joints, causing painful swelling, stiffness, and a loss of function in fingers, wrists, or other joints. Often thought to be triggered by factors such as smoking and stress, it’s now known to be related to gut health; i.e., diet related, ultimately.
A specific type of gut bacteria, Prevotella copri, is found in over 75% of those newly diagnosed. When lab animals were implanted with Prevotella copri, they developed symptoms of rheumatoid arthritis. While this is not enough for scientists to develop a cure, it does give them clues toward developing new treatments, treatments that will almost certainly target gut microbial dysbiosis.
Ankylosing Spondylitis –
Ankylosing Spondylitis is an autoimmune disease that attacks the spaces between vertebrae in the spinal column, hip joints, and other locations throughout the body. It’s a disfiguring, painful disease that’s closely associated with the gut microbe Klebsiella pneumoniae. Beneficial microbes Bifidobacteria, Lactobacilli, and other core species prevent Klebsiella from turning invasive.
While Klebsiella pneumoniae is a normal inhabitant of the human gut, it’s often associated with urinary tract infections, upper respiratory tract infections, and wound site infections. When it grows uncontrollably in the respiratory tract it can lead to deadly pneumonia.
The microbe’s association with ankylosing spondylitis has a clear genetic factor, with 90% of patients expressing the HLA-B27 genotype. One hypothesis put forth is that this genetic signal could trigger the disease by enhancing the growth and perpetuation of the Klebsiella microbes in the bowel. In an attempt to slow the growth of the now pathogenic bacteria, the immune system mistakenly attacks the human tissues, thus causing the disease. Strings of protein in Klebsiella bear resemblance to human joint tissue. This molecular mimicry is the underlying mechanism behind all autoimmune disease and a growing number of modern diseases that heretofore had no clear medical pathophysiology—such as essential hypertension. 
A common treatment for ankylosing spondylitis is to restrict all fermentable fiber from the diet in order to starve the gut microbes, achieving results similar to the overuse of antibiotics, or the practice of very low carbohydrate and ketogenic diets.  This approach may have short-term therapeutic value but an unforeseen drawback may be further damaged immunity and gut health in the long term, leading to unintended consequences. The immune system lines the entire gut and atrophies without butyrate and contact from the beneficial microbes that regularly consume fermentable fiber.
Type 1 Diabetes Mellitus (T1D) –
Type 1 diabetes results from autoimmune destruction of insulin-producing beta cells in the pancreas. As has been harped on plenty, factors that influence gut health—for better or worse—are factors that ultimately influence the function of the immune system—for better or worse. It’s so closely tied together, it’s a testament to the intricacies of the gut, gut microbes, and our resulting immune system. Gut bugs modulate its function through what is essentially training the immune system—in particular T cells—as mentioned earlier.
The gut and pancreas also share several critical links and so problems with the gut are often reflected in the pancreas. Altered gut microflora have been linked to T1D in animal and human studies, and are normally thought to be a function of intestinal inflammation, gut permeability, and food allergies. Children with T1D are more susceptible to certain infections and do not normally develop tolerance to cow’s milk. These complex interactions are currently the target of new approaches to prevention and treatment.
Hashimoto’s Thyroiditis –
“Hashi’s” is a condition where the thyroid gland is attacked by a combination of immune processes that can manifest as high or low thyroid levels, but most usually the latter. It has the distinction of being the very first disease to be recognized as an autoimmune condition.
Mounting evidence suggests that not only intestinal pathogens, but symbiotic ones can influence an overblown immune response against thyroid tissue. And more recent studies reveal that not only the gut commensals, but also oral microorganisms such as periodontal bacteria, may play a role.
To muddy the waters even further, an association between celiac disease or gluten sensitivity and autoimmune thyroid disorders is well established, with about ten times as many with gluten issues also having thyroid issues than is observed in the general population. Curiously but not surprisingly, this link may exist due to a molecular similarity between gliadin, the protein portion of gluten and thyroid tissue. In all, one intuitive way to regard the process is that a leaky gut, as addressed previously, allows gliadin into the bloodstream where it’s attacked by the immune system as a foreign invader, with “similar looking” thyroid tissue getting caught in the crossfire.
What remains to understand is which strains of intestinal flora help, and which hurt. As we’ve seen a number of times thus far, it’s not as simple as good guy vs. bad guy. “Good guys” can be bad if there are too many of them or they’re out of proportion with other “good guys.” And “bad guys” can be non pathologic if still other “bad guys” (or “good guys”) are keeping them in check. A 2012 paper demonstrates just how complex the picture is.
Multiple lines of evidence have demonstrated that probiotic organisms such as Bifidobacterium and Lactobacillus confer health benefits on the host. For instance, oral administration of probiotics to mice induced IL-10 production and prevented the development of autoimmune diseases including type 1 diabetes and colitis. This probiotic-induced anti-inflammatory effect is reportedly mediated by dendritic cells. However, series of in vivo and in vitro studies have demonstrated that certain probiotic strains exacerbated colitis and encephalomyelitis, enhanced interferon-γ (IFNγ) production and reduced regulatory T cell (Treg) activity, indicating that attention should be paid when choosing a probiotic strain to treat autoimmune disorders. In experimental autoimmune thyroiditis (EAT), a murine model of Hashimoto’s thyroiditis, probiotic strains Lactobacillus rhamnosus HN001 and Bifidobacterium lactis HN019, which had been shown to enhance splenocyte IFNγ production in mice, exhibited neither stimulatory nor inhibitory effect on the disease development. Taken collectively, the presence and the role of intestinal dysbiosis and the effect of alteration in the gut microbial composition remain to be investigated in Hashimoto’s thyroiditis.
Unfortunately, the standard of treatment for low thyroid (hypothyroidism) is effective enough for most people by the administration of synthetic thyroid hormone to treat the symptom, that little has been done in the mainstream to investigate the underlying cause: in order to develop more fundamental therapies or recommended lifestyle changes for better management, or even a cure.
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