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Autoimmune Diseases and the Gut Biome

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:

AUTOIMMUNE DISEASES

A well established aspect of the gut microbiome is its close relationship with host immunity, essentially comprising 70% of the immune system.[1] 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
* Alopecia
* 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
* Endometriosis
* Fibromyalgia
* Infertility
* 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
* Lupus
* Meniere’s Disease
* Mixed Connective Tissue Disease (MCTD)
* Multiple Sclerosis
* Myasthenia Gravis
* Narcolepsy
* Pemphigus
* Pernicious Anemia
* Polyarteritis Nodosa
* Polymyositis
* Primary Biliary Cirrhosis
* Psoriasis
* Raynaud’s Disease
* Reiter’s Syndrome
* Rheumatoid Arthritis
* Sarcoidosis
* Scleroderma or CREST Syndrome
* Silicone Immune Toxicity Syndrome
* Sjogren’s Syndrome
* Stiff-Man Syndrome
* Type 1 Diabetes
* Ulcerative Colitis
* Vascular Dementia
* Vasculitis
* Vitiligo
* 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.[2] 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.[3] [4]

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.[5] [6] 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.[7]

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.[8]

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.[9] 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.[10]

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.[11] Curiously but not surprisingly, this link may exist due to a molecular similarity between gliadin, the protein portion of gluten and thyroid tissue.[12] 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.[13]

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.
________________
[1] Wu, Hsin-Jung, and Eric Wu. “The role of gut microbiota in immune homeostasis and autoimmunity.” Gut Microbes 3.1 (2012): 4-14.
[2] “HLA-B27 – Wikipedia, the free encyclopedia.” 2004. 17 Aug. 2014 <http://en.wikipedia.org/wiki/HLA-B27>
[3] Schwimmbeck, PETER L, DT Yu, and MB Oldstone. “Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter’s syndrome. Molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease.” The Journal of experimental medicine 166.1 (1987): 173-181.
[4] Tervaert, JWC. “Hypertension: an autoimmune disease[quest] – Nature.” 2011. <http://www.nature.com/hr/journal/v34/n4/full/hr201115a.html>
[5] “LOW STARCH DIET.” 2012. 3 May. 2014 <http://www.spondylitis.org/about/low_starch_diet_summer2012_spondylitis_plus.pdf>
[6] Ebringer, A, and C Wilson. “The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis.” Clinical rheumatology 15.1 (1996): 62-66.
[7] Rashid, T. “The Link between Ankylosing Spondylitis, Crohn’s Disease …” 2013. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678459/>
[8] Vaarala, O. “Gut microbiota and type 1 diabetes.” The review of diabetic studies: RDS 9.4 (2011): 251-259.
[9] Jaimie Dalessio. “Gut Bacteria May Prevent Type 1 Diabetes – Digestive Health Center …” 2013. 19 Jan. 2014 <http://www.everydayhealth.com/digestive-health/gut-bacteria-may-prevent-type-1-diabetes-2306.aspx>
[10] Mori, K. “Does the gut microbiota trigger Hashimoto’s thyroiditis?.” 2012. <http://www.ncbi.nlm.nih.gov/pubmed/23200063>
[11] Sategna-Guidetti, C. “Autoimmune thyroid diseases and coeliac disease.” 1998. <http://www.ncbi.nlm.nih.gov/pubmed/9872614>
[12] “The Gluten-Thyroid Connection – Chris Kresser.” 2011. 18 Dec. 2014 <http://chriskresser.com/the-gluten-thyroid-connection>
[13] Mori, K. “Does the Gut Microbiota Trigger Hashimoto’s Thyroiditis …” 2012. <http://www.discoverymedicine.com/Kouki-Mori/2012/11/27/does-the-gut-microbiota-trigger-hashimotos-thyroiditis/>

Richard Nikoley

I'm Richard Nikoley. Free The Animal began in 2003 and as of 2021, contains 5,000 posts. I blog what I wish...from health, diet, and food to travel and lifestyle; to politics, social antagonism, expat-living location and time independent—while you sleep—income. I celebrate the audacity and hubris to live by your own exclusive authority and take your own chances. Read More

14 Comments

  1. pzo on December 18, 2014 at 21:06

    “Holy shit!” doesn’t even come close.

    In matters of diet and health, we are barely moving out of the Dark Ages.

    • sdiguana on December 19, 2014 at 05:39

      Amen to that. I find it interesting that the whole gluten thing is tied to hashi’s. Its hard for people to avidly avoid it when the damage is so subtle vs the gut wrenching pain induced by a more overt disease. Possibly why we have so much hashi’s here.

    • Richard Nikoley on December 19, 2014 at 07:46

      Pzo:

      You exactly express my entire aim and goal for this book. Not a diet, health or fix your gut book. It’s to get people to go wow, I had no idea this shit was so important and shows how much we don’t know and understand.

  2. Kate on December 19, 2014 at 07:13

    Richard – Thought you might find this interesting… although not entirely related to the subject at hand. I’ve been battling autoimmunity and immunodeficiency for my whole life. My IgG levels were on a steep decline after my year of VLC. Over the past few months I’ve made a major effort to add potatoes and beans back into my daily diet, and I have done several “courses” of RS and probiotics. FOR THE FIRST TIME IN MY LIFE my IgG levels have been nearing the normal range. I was at 490 in September (pre-resistant starch experiment) and 3 months later, I’m up to 690 (700 is the low end of normal). Coincidence? I’m thinking not.

    • Richard Nikoley on December 19, 2014 at 08:17

      Good news Kate.

      I’m certainly not touting this will help everdody, only that clearly, it appears to help some and thus, is probably not harmful to most or even anyone.

  3. Jane Karlsson on December 21, 2014 at 06:30

    “This molecular mimicry is the underlying mechanism behind all autoimmune disease …”

    I would just like to point out the following. In autoimmune disease, proteins get exposed to the immune system which would normally be shielded from it. This appears to be the primary problem, not the molecular mimicry. Dead and dying cells need to be cleared efficiently.

    If it’s true in humans as in rodents that phagocytic cells are very sensitive to copper deficiency, autoimmune disease may be the result of mild lifelong copper deficiency, which according to copper researcher Leslie Klevay, is so common most Americans have it.

    There are nutrition bloggers who believe copper overload is more of a problem. This is probably because during inflammation, blood copper rises. This does not mean the copper is causing the disease, it means it’s needed for tissue repair.

  4. Gassman on December 21, 2014 at 12:09

    I have RA. I know several folks that have at least one of the listed autoimmune conditions listed above. I’m doing well enough with my RA that my rheumatologist has declared me in remission. I take Plaquenil 200mg 2x daily. I have been gluten free for about 3 years. Doc wants me to stay on plaquenil as a preventative. I’d like to stop it, as I think my remission is due more to the gluten free lifestyle. Here’s what chaps my backside: as I said, I know folks with autoimmune disorders listed above, and none of their doctors have suggested a modified or gluten free diet.

    • Richard Nikoley on December 21, 2014 at 13:09

      Yep, the age old problem of treat the symptom, disregard the cause. It’s like giving a wheelchair to someone with a broken leg.

  5. James on December 23, 2014 at 10:18

    I have ankylosing spondylitis… I have no idea how to treat it because I don’t want to starve my biome but the only thing I can feed it with is green plantains! But even when they’re a tiny bit ripe (which is at least 80% of the time) I get symptoms (joint pain, skin, anxiety).

    I think it’s possible that the Klebsiella has taken over and made my colon less acidic – klebsiella thrives at a pH of 7.2 and normal colonic pH is somewhere. from 5.5 – 7. How could I make my colon more acidic without feeding Klebsiella?

    Also, I’ve done FMT with 3 different people and every time, I feel good for a few days, then I go back to feeling like shit. I think maybe the good bacteria can’t take hold because the colon is not acidic enough. Help me Richard!!!

  6. FredSonoma on January 17, 2015 at 08:02

    Does anyone have thoughts on a product like GI Microb – X? ) It’s a “botanical blend” that’s supposed to kill bad bacteria and protect good bacteria. For someone with Ankylosing Spondylitis with no end in sight, could this be hope? Or a hoax?

  7. girl on September 21, 2017 at 03:50

    I doubted this comment: “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.” I am thinking of the autoimmune patients I’ve met. I can think of some who eat a standard American diet, or who resort to Frankenfoods when convenient, but I can think of many more who were brought up eating the sort of scratch-cooked foods recommended by the health food movements of the 70s and 80s. Others continue to eat traditionally-prepared foods from their country-of-origin. I don’t know if genetic susceptibility taught their families to eat well, or if as individuals they made sure to retain the healthy diets that many people eschew in their 20s and 30s because of their diagnoses, but they honestly eat better than their peers. I would look rather to taking antibiotics.

  8. HPSon on March 10, 2018 at 06:51

    I have Klebsiella Pneumoniae in my gut, according to recent stool testing, and guess what – I have recently been diagnosed with Undifferentiated Connective Tissue Disease. Although I don’t know exactly how to treat it, but merely knowing and understanding the connection feels liek a huge breakthrough. I have had a model diet all my life, was never allowed junk food as a child, all home made fresh food, tons of vegetables. I put my autoimmune disease down to neither of my parents being breastfed, nor myself, and many many courses of antibiotics (up to a year at a time) to treat skin conditions present from birth. I suspect my grandparents on one side weren’t breastfed as they were dairy farmers and were probably moved onto cow’s milk young. There is autoimmune thyroid illness in that side of the family, and Chron’s and colitis in the other side – also all raised eating extremely good nutrient rich diets. Something messed with them, but I don’t know what, not food perhaps antibiotics and prior to their use extreme poverty and stress may have affected their biomes.

    • John R Froude on March 12, 2018 at 05:45

      I see nothing but confirmation and ascertainment bias.
      The list of “autoimmune diseases” is seriously ill informed.
      These diseases are on the increase but what about the diseases that are on the decrease such as Rheumatic Fever, Scoliosis, all treatable infectious diseases say Tuberculosis.
      How about the possibility that there is more Ankylosing Spondylitis say, because you survived the lethal infections your ancestors would have died from.
      This argument would be like someone saying in the middle of the Aids epidemic Oh the incidence of Aids has gone it can only be due to our lousy diet.
      Show me the evidence. Please.

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