GLUTEN SENSITIVITY & AUTOIMMUNITY

GLUTEN SENSITIVITY AS RELATED TO AUTOIMMUNITY

"The term gluten intolerance may refer to three types of human disorders: autoimmune celiac disease, allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of proteins present mostly in wheat, but also in barley, rye and oats. It has been suggested that in NCGS gluten-related peptides enter the systemic circulation and cause extraintestinal manifestations such as ataxia, neuropathy and encephalopathy. Moreover, it has been proposed that gluten causes depression, anxiety, autism and schizophrenia in patients with NCGS, and also reported that psychosis might be a manifestation of NCGS. Nowadays, gluten-related disorders have often been recognized as commonly mimicking irritable bowel syndrome because of the similar symptoms such as abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation). Furthermore, the microbiome may also play a role in the pathogenesis of NCGS. Gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of gluten intolerance in genetically-susceptible individuals.  There is currently only one proven effective way of treating celiac disease and NCGS—a gluten free diet."   Cherry-picked (as are all studies quoted in this post) from last month's issue of Nutrients (Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities)

"Approximately 50 million Americans, 20 percent of the population or one in five people, suffer from autoimmune diseases. Women are more likely than men to be affected; some estimates say that 75 percent of those affected–some 30 million people–are women."  From the American Autoimmune Related Diseases Association

Despite the fact that we've known for decades that wheat is intimately related to autoimmunity and the numerous autoimmune diseases associated with, the medical community largely continues to ignore their own research.  This doesn't even begin to take into account NCGS, which studies show, is not even believed to be a real entity by over half of all treating physicians (HERE).  For instance, the July issue of the medical journal Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz (Non-Allergic Gluten Sensitivity. A Controversial Disease or not yet Sufficiently Explored?) concluded that, "The avoidance of wheat, gluten and other cereal products is a growing phenomenon in industrialized countries. There exists a significant proportion of people reporting at least subjectively significant complaints and quality of life improvements after switching to a wheat- or gluten-free diet. The absence of clear diagnostic autoimmune or allergic criteria in these wheat sensitive patients has resulted in the description of non-celiac gluten sensitivity. It is clinically detectable in only very few individuals and may manifest with either intestinal, extra-intestinal or neurovegetative and psychosomatic symptoms."  It is important to realize that despite our ability to test for it, NCGS is both real and potentially severe as described by the previous sentence.

The evidence linking autoimmunity to Celiac Disease is overwhelming.  The question now becomes, how much autoimmunity can be intimately linked to NCGS?  A study from the September issue of Gastroenterology (High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies) went a long way toward answering this question.  "We evaluated the prevalence of autoimmune diseases among patients with nonceliac wheat sensitivity (NCWS), and investigated whether they carry antinuclear antibodies (ANA).  In the retrospective analysis, similar portions of subjects with NCWS (29%) and CD (29%) developed autoimmune diseases (mainly Hashimoto's thyroiditis, 29 cases).....  In the prospective study, 24% of subjects with NCWS, 20% of subjects with CD developed autoimmune diseases. In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS, 24% of subjects with CD....  in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with CD...."

The point here is that NCGS is at least as associated with autoimmunity as Celiac Disease is as measured by the ANA or antinuclear antibody test --- and in some cases more so.  The ANA is an inexpensive blood test that can be added to the panel next time you have blood work done.  Although vague as far as what it tells you (it gives you an idea of whether your body is making antibodies against self, although it does not tell you what specific tissue is being attacked), it at least provides a starting point.  Now; allow me to show you some studies concerning GLUTEN and AUTOIMMUNITY.

• GLUTEN SENSITIVITY IS RELATED TO THE MICROBIOME:  Again, since virtually everything else is related to GUT HEALTH, why not Gluten Sensitivity?  Actually, there are tons of studies on this specific topic, including one from last month's issue of Gastroenterology (Duodenal Bacteria From Patients with Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity).  This study revealed that, "Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, and additional environmental factors related to unfavorable alterations in the microbiota have been proposed."  Did you catch that?  GENETICS alone won't do it; there has to be other factors at play.  Although there are any number of reasons that more people than ever are reacting to Gluten (HERE), I would have to say that the 'alterations in the microbiota' that we refer to in the medical community as "DYSBIOSIS" are arguably biggest.  "Small intestinal bacteria exhibit distinct gluten metabolic patterns, increasing or reducing gluten peptide immunogenicity. This microbe-gluten-host interaction may modulate autoimmune risk in genetically susceptible persons and may underlie the reported association of dysbiosis and CD." An Italian study from the July issue of the International Journal of Food Microbiology (Salivary and Fecal Microbiota and Metabolome of Celiac Children Under Gluten-Free Diet) revealed something similar.  "Dysbiosis can precede the CD pathogenesis and/or persist when subjects are on GFD.  Salivary microbiota and metabolome differed between healthy and celiac children treated under GFD for at least two years.  Different studies showed bacterial dysbiosis at duodenal and/or fecal level of patients with active untreated CD compared to healthy subjects. The ratio of protective anti-inflammatory bacteria such as Lactobacillus-Bifidobacterium to potentially harmful Bacteroides-Enterobacteriaceae was the lowest in" the treatment group. Even though these and many of the studies we will discuss today specifically pertain to Celiac Disease (CD), it is critical to understand that.......

• GLUTEN CAN BE RELATED TO AUTOIMMUNITY EVEN IN THE ABSENCE OF CELIAC DISEASE:  You've seen many studies on this but feel like I need to belabor the point.  When doctors talk to patients, they will often tell them that while certain health-related issues might be linked to Celiac, Celiac is not their problem because they didn't test positive, thus their problem has nothing to do with Gluten.  As I've shown you repeatedly (HERE), this is a dangerous way of thinking.  The difference between Celiac Disease and Non-Celiac Gluten Sensitivity is simple to understand.  The only thing that a Celiac diagnosis really means is that your own immune system is making antibodies against the villi / microvilli of the Small Intestine, creating damage that can be seen on biopsy.  Knowing this makes it simple to understand why.......

• GLUTEN IS RELATED TO INFLAMMATION, ANY NUMBER OF THE SYNDROMES IN THE "LEAKY" FAMILY, AND AUTOIMMUNITY WITHIN THE ENDOCRINE SYSTEM:  Rather than belabor this point, I'll simply ask you to look at the first link at the top of the post, as well as my post on THE LEAKIES AS RELATED TO GLUTEN. If you are dealing with Chronic Pain or Chronic Illness, it is imperative for you to understand this bullet point.  And since we are talking about Autoimmune Diseases today, the link between Gluten and Autoimmunity is nothing new.  In fact, it was something being discussed by leaders in the field of natural medicine seven decades ago (HERE).  The Swiss journal, Digestive Diseases, published a study in April of 2015 called Celiac Disease and Endocrine Autoimmunity.  In it they concluded that, "Endocrine autoimmunity is prevalent in patients with CD. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, are also the major genetic determinants of CD....  Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission."  Firstly, this last sentence is not true in any way, shape, or form as you will see at the end of this post.  And secondly, as you may have already guessed from this short list, one of the top autoimmune diseases being linked to NCGS is......

• GLUTEN SENSITIVITY & AUTOIMMUNE THYROID:   Although many are unaware, the vast majority of thyroid problems are autoimmune (HERE).  In fact, earlier this year, the Indian Journal of Endocrinology and Metabolism (Celiac Autoimmunity in Autoimmune Thyroid Disease is Highly Prevalent with a Questionable Impact) stated, "It has been hypothesized that the exposure to gluten in patients with CD triggers off autoimmunity against other tissues in the body.  CD patients are prone to a number of other autoimmune disorders.  The prevalence of autoimmune thyroid disease (AITD) is 10–12% in the general population worldwide.  280 consecutive patients with AITD attending the thyroid out-patient department of a tertiary care hospital were screened for the presence of tissue transglutaminase antibodies.  Conclusions: The prevalence of CD in patients with AITD is much greater than in the general population."  This follows closely with the results seen when the May issue of Liver and Digestive Diseases published a Dutch study called A Large Variety of Clinical Features and Concomitant Disorders in Celiac Disease - A Cohort Study in the Netherlands.  In this study the authors revealed that just over one quarter of those diagnosed with CD had autoimmune diseases (immune mediated diseases or IMD).  The third most common of these, just a few tenths of a percentage point behind the first and second place diseases, was THYROID DISEASE.  What was in first place.......? 

• GLUTEN AND TYPE I DIABETES:  Not to be confused with TYPE II DIABETES, Type I Diabetes is an autoimmune disease manifesting in the body attacking various types of cells and enzymes in the pancreas.  Although the cause of Type I Diabetes is unknown, it is said, like most other autoimmune diseases, to be a combination of genetic and "ENVIRONMENTAL" factors.  What are some of these environmental factors?  The April 2015 issue of the Indian Journal of Endocrinology and Metabolism revealed that, "The one definite environmental factor is congenital rubella, because of which a subset of children subsequently develop type 1 diabetes. The predisposing factors are viruses, gluten and cow's milk. The protective factors include gut flora, helminths [worms], viral infections, and Vitamin D."  Isn't it interesting that viral infections can be both preventative and predisposing at the same time and that worms can be protective?  Another study, this one from the May 2015 issue of Diabetologia (A Model for the Role of Gut Bacteria in the Development of Autoimmunity for Type 1 Diabetes) sums up the whole mess perfectly.  "Studies suggest a testable model whereby a diet high in fat and gluten and low in resistant starch [HERE] may be the primary driver of gut dysbiosis. This dysbiosis may cause a lack of butyrate production by gut bacteria, which, in turn, leads to the development of a permeable gut followed by autoimmunity."  Everything we have been discussing rolled into one neat package.  Just remember that a HIGH FAT DIET is a wonderful thing as long as it is high in good fats.

• GLUTEN & TYPE I DIABETES PART II:  The September 2015 issue of Nutrients (The Role of Gluten in Celiac Disease and Type 1 Diabetes) showed us that, "Celiac disease and type 1 diabetes are autoimmune conditions in which dietary gluten has been proven or suggested to play a pathogenic role."  How do the authors suggest this problem be addressed?  One way mentioned was, "A gluten free diet should cause no side effects, since gluten has limited nutritional value."   Getting off and staying off gluten is important because, "Digested gluten interacts with epithelial cells in the small intestine and triggers the disruption of tight junctions. The consequent increased intestinal permeability leads to...... a high rate of comorbidity between these two autoimmune diseases and their rapidly increasing prevalence in the last few decades.... relating intestinal dysbiosis to various diseases, among which CD is included. It has been shown that the dysbiosis characterizing active CD patients is partially reversible and linked to the presence of gluten in the diet."  A year ago next month, the Canadian Journal of Diabetes (Celiac Disease and Type 1 Diabetes in Adults: Is This a High-Risk Group for Screening?) reiterated these findings by concluding that, "The association between celiac disease (CD), an autoimmune condition involving intestinal inflammation related to gluten ingestion, and type 1 diabetes has long been recognized. CD prevalence rates 4 to 6 times greater in adults with type 1 diabetes than in the general population. Much of the existing literature focuses on important implications related to the impact of a gluten-free diet on short-term outcomes in metabolic control and quality of life. Canadian Diabetes Association guidelines recommend targeted CD screening in patients with type 1 diabetes who have classic symptoms, such as abdominal pain, bloating, diarrhea, unexplained weight loss or labile metabolic control; however, a significant proportion (40% to 60%) of patients may have mild or absent symptoms. Recent evidence suggests that adult patients with both conditions are at higher risk for diabetes microvascular comorbidities, increased mortality and impaired bone health if the CD is untreated."  The icing on the cake is that you don't have to sit back, totally helpless, letting the disease dictate your life.  July's issue of Springer Plus (Potential Beneficial Effects of a Gluten-Free Diet in Newly Diagnosed Children with Type 1 Diabetes) showed how a, "Gluten-free diet is feasible in highly motivated families and is associated with a significantly better outcome as assessed by HbA1c and IDAA1c."  BTW, one of the more common issues I noticed being tied to both CD and Type I Diabetes is......

• GLUTEN & OSTEOPOROSIS:  After looking at over 200 studies on the subject, authors from the University of Connecticut published their meta-analysis (Bones of Contention: Bone Mineral Density Recovery in Celiac Disease—A Systematic Review) in the May 2015 issue of Nutrients.  "Metabolic bone disease is a frequent co-morbidity in newly diagnosed adults with celiac disease (CD), an autoimmune disorder triggered by the ingestion of dietary gluten. Approximately 75% of newly diagnosed patients with celiac disease have low bone mineral density. And when matched by age and gender to a non-affected population, celiac patients have a 40% greater risk for bone fracture   Gluten-free diet adherence resulted in partial recovery of bone density by one year in all studies, and full recovery by the fifth year. No treatment differences were observed between the gluten-free diet alone and diet plus bisphosphonates in one study."   As for bisphospsphonates, we shouldn't be surprised (HERE).  This month's issue of Joint, Bone, and Spine (Osteoarticular Manifestations of Celiac Disease and Non-Celiac Gluten Hypersensitivity) says simply that, "Celiac disease is a chronic inflammatory autoimmune enteropathy based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The global prevalence of 1% to 2% represents only the tip of the iceberg.  The diagnosis is difficult and often delayed because the clinical variability is very large, ranging from digestive clinical presentation "classic" to "atypical" symptoms, often extra-intestinal, that are sometimes attributed to a concomitant disease or a complication. Among them, there are frequent musculoskeletal manifestations such as osteoporosis and osteomalacia.  Non-celiac gluten intolerance is a new entity defined by symptomatology similar to that of celiac disease induced by the ingestion of gluten and disappearing after crowding-out [GFD], among patients without specific antibodies and without intestinal lesion of celiac disease."  OSTEOPOROSIS affects bones, and so does......

• GLUTEN & ARTHRITIS:  There is an overwhelming amount of information concerning the relationship of wheat to various forms of arthritis.  One of last year's issues of Acta Chirugiae Orthopedicae et Traumatologiae Cechoslovaca (Bone and Joint Involvement in Celiac Disease) said that, "Celiac disease (gluten-sensitive enteropathy) is currently regarded as a multisystem autoimmune disorder; its clinical signs and symptoms do not involve merely the gastrointestinal tract but are associated with several other medical specialties, including orthopaedics and traumatology. In orthopaedic and trauma patients, celiac disease should be suspected in the following diagnoses: osteomalacia, premenopausal osteoporosis, post-menopausal osteoporosis more severe than expected and refractory to medication, osteoporosis in men under 55 years of age, recurrent bone fractures in the limbs, large joint arthralgia or arthritis of unclear aetiology, erosive spondyloarthropathy particularly in patients with the history of chronic diarrhoea, anaemia or associated autoimmune disorders (type 1 diabetes mellitus or autoimmune thyreopathy), and in women with secondary amenorrhea or early menopause. The orthopaedist or trauma surgeon should be aware of suspected celiac disease in patients who do not respond adequately to the standard treatment of pain related to the musculoskeletal system, in patients with recurrent fractures of the limb bones and in young patients with suspected secondary osteoporosis."  I don't care how you slice it, that was a heck of a list!

• GLUTEN & ARTHRITIS PART II:  Completed at Mexico's Colegio Mexicano de Reumatología and published in January's issue of Spain's Rheumatologia Clinica, this study (Non-celiac Gluten Sensitivity and Rheumatic Diseases) looked specifically at NCGS as it pertains to arthritic problems.  The authors stated, "Non-celiac gluten sensitivity is an emerging entity with symptoms similar to celiac disease, but without specific diagnostic tests.  Non-celiac gluten sensitivity (NCGS) is an emerging entity characterized by gluten-related intestinal and extraintestinal symptoms in patients with negative CD tests who, thus, are not considered to be celiac patients.  With regard to the symptoms, CD and NCGS are indistinguishable.  NCGS is estimated to affect around 5% of the population.   However, the dichotomous working approach of considering CD and NCGS as different entities does not depict the complexity of a disease that is probably the expression of a biological continuum. There are many examples of patients who, following strict criteria, cannot be considered celiacs, but whose profile overlaps substantially with CD.  The idea that has guided the clinical development dealt with in this article is that NCGS occurs frequently and is the cause of a number of rheumatic complaints.  It seems reasonable to think that, like CD, NCGS is also associated with autoimmunity."  After discussing various health issues known to be associated with NCGS (FIBROMYALGIA, RHEUMATOID ARTHRITIS, DEGENERATIVE ARTHRITIS, CHRONIC LOW BACK PAIN, CHRONIC SACROILLIAC PROBLEMS, Psoriatic Arthritis, Ankylosing Spondylitis, along with a slew of other Autoimmune Diseases), the authors specifically mentioned that, "The use of anti-inflammatory agents, proton pump inhibitors and psychotropic drugs was also minimized because of their secondary effects on the small intestine and on the central nervous system."  What they are referring to here, folks, are THE BIG FIVE (opiods were also mentioned), ACID REFLUX DRUGS, and ANTIDEPRESSANTS.

• GLUTEN & ARTHRITIS PART III:  Last February's issue of Gastroenterology Research (Coeliac Disease With Rheumatoid Arthritis: An Unusual Association) revealed the association between Gut Health (Leaky Gut & Microbiome) and autoimmunity in general.  "Coeliac disease has a significant association with many autoimmune disorders. It shares many common genetic and immunological features with other autoimmune diseases. Gluten, a gut-derived antigen, is the driver of the autoimmunity seen in coeliac disease. The altered intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut. Gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including rheumatoid arthritis."  Bottom line, if you have chronic joint or back pain and have not done a GLUTEN-FREE ELIMINATION DIET (the correct way, by eliminating CROSS-REACTORS and NIGHTSHADES) and are still suffering, I can't really offer you any help since you are skipping the first and most important of the factors in solving your gluten-related problems.  Speaking of gluten-related problems, you need to realize how many of these gluten-related autoimmune issues are neurological, including.......

• GLUTEN AND CEREBELLAR ATAXIA:  We've known for years that the huge majority of gluten-related symptoms are extra-intestinal (people don't have belly aches, bloating, gas, diarrhea, constipation, etc), with most of these tending to be neurological (HERE).  One of the most well-documented of these is a potential mimic of PARKINSON'S DISEASE known as Cerebellar Ataxia.  Cerebellar Ataxia presents clinically as an inability to coordinate balance, gait, and extremity and eye movements.  Pay attention as the authors of Guidelines for Treatment of Immune-Mediated Cerebellar Ataxias (from the November 2015 issue of Cerebellar Ataxias) reveals one of the body's prime targets for autoimmune reactions.  "Accumulating evidence suggests that the cerebellum is one of the main CNS targets of autoimmunity, as demonstrated by the high prevalence of cerebellar degeneration amongst neurological syndromes."  I would argue that at least half of the ataxic syndromes mentioned (Gluten Ataxia and Hashimoto's Encephalopathy) will likely respond to a GFD.  In March of 2015, seventeen scientific / medical experts got together to create a consensus paper, which was published in the journal Cerebellum.  The authors concluded that, "In patients with immune-mediated cerebellar ataxias, a part of the deficit appears to remain reversible because they are sometimes treatable."   Reversible is cool!  How are they treated?  "In the case of gluten ataxia, strict adherence to a gluten-free diet."   As bad as Cerebellar Ataxia is, there are neruological syndromes that are much worse.  One of these is......
  

• GLUTEN & AMYTROPHIC LATERAL SCLEROSIS:  Known as Lou Gehrig's Disease, ALS attacks the part of your nervous system that sends the messages telling your body what to do and how to move.  The result is stiffness, weakness, twitching, atrophy, and eventually a total inability move, speak, swallow, or even breathe.  Needless to say, the disease is 100% fatal, usually within a few years, although some like Stephen Hawking, have lived with it for well over half a century.  This is another of the cases where Epigentics trump Genetics as less than one in ten cases is passed on through genes.  The single biggest risk factor for ALS?  Head injuries, which are themselves strongly associated with autoimmunity (HERE).  In the SUMMER OF 2015, JAMA Neurology published a study called Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis.  The authors stated that, "Many patients with gluten ataxia produce antibodies toward the newly identified neuronal transglutaminase 6 (TG6). Two case reports described patients initially diagnosed with amyotrophic lateral sclerosis (ALS) and ultimately with celiac disease who improved with a strict gluten-free diet"  In this study, physicians and researchers at Israel's Tel Aviv University compared looked at 150 consecutive ALS patients, testing them for the TG6 antibodies.  The authors concluded that, "The data from this study indicate that, in certain cases, ALS might be associated with autoimmunity and gluten sensitivity."