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The Gluten-Gut-Brain Connection

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Going gluten-free seems to be the newest dietary fashion that many people and even some pampered pets are flocking to. This trend has taken hold as the number of new cases of celiac disease and gluten sensitivity have skyrocketed over the past several years. Is gluten intolerance really all that common or is this just marketing hype and hyperbole?

More to the point, who really needs to be on a gluten-free diet? And why does such a question matter to me, a simple country psychiatrist?

To answer this question, let me give you a bit of background on the gut-brain connection.


We have known for centuries (although modern medicine sometimes forgets) of the inextricable connection between our bodies and brains. Lawrence Sterne’s beloved character, Tristram Shandy, summarized it eloquently back in 1761: “A man’s body and his mind, with the utmost reverence to both I speak it, are exactly like a jerkin [jacket], and a jerkin’s lining; – rumple the one, -you rumple the other.”

Only much more recently, however, have we begun to appreciate the elaborate gut-brain connection and its relationship to our overall health and happiness. Indeed, your gut may very well be the most important factor in determining your overall well-being.

For example, did you know that:

  • Between 70-80% of your immune active cells reside in your intestinal tract;
  • Your gut is responsible for protecting you against harmful bacteria, yeast, viruses, and parasites;
  • 75% of your brain chemicals (neurotransmitters such as serotonin, norepinephrine, and dopamine) are made in your gut;
  • A healthy gut is necessary for proper digestion and absorption of nutrients needed to supply the entire body with the required building blocks for energy, growth, and repair;
  • Your gut in metabolically more active than your liver?

Multiple converging lines of research have identified a direct connection between the gut, activities of the brain, such as mood and behavior, and the micro-organisms that inhabit your gastrointestinal tract (gut microbiota). For example, epidemiologic studies in humans show that negative emotions are often associated with the development of acute gastrointestinal (GI) infections, and conversely, chronic GI inflammation has multiple effects on mood, including symptoms of depression and fatigue. Moreover, risk factors for the development of irritable bowel syndrome include adverse life events, depression, and excessive worry.

It turns out that the specific composition of your microbiota can determine whether your immune response to life stressors is healthy and “right-sized,” excessive and exaggerated (inflammation), or inadequate and insufficient (infection).

Many of us, unbeknownst to ourselves, suffer from an alteration of these all-important gut microbes. This condition is called dysbiosis and can be caused by many things. This dysbiosis in turn triggers, aggravates, or perpetuates (or all three) the degenerative diseases to which you are susceptible.

The flow, so to speak, according to this theory proceeds as follows: Life stressors bring about alterations in your gut microbiota that cause you, among other things, to have increased intestinal permeability (“leaky gut”). As such, “bad” bugs (certain viruses, bacteria, yeast, parasites) and food stuffs (gluten) that normally would pass right through now gain entrance into your system. Because 80% of your immune cells reside just inside the lining of your gut, these foreign microbial and food invaders evoke an all-out immune attack. Under normal conditions, a healthy balance of microbial powers in your gut will “right-size” this immune assault. Unfortunately, the very alteration in gut microbiota (dybiosis) that started the whole process now lacks the ability to regulate your immune response. A vicious cycle of inflammation, gut leakiness, and more inflammation ensues. Said inflammation then becomes the missing link and unifying theory of the connection between your individual disease susceptibilities (genes and early life experiences), life stressors, and your specific diseases of civilization.


There are many interpersonal, environmental, and dietary stressors that can affect your gut. One that has been in the news of late and you’ve no doubt wondered about is gluten.

Gluten, not actually a single molecule, is a structural component of not only wheat but many other grassy cereal grains as well: rye, spelt, kamut, barley, bulgur wheat, durum, einkorn, farro, graham, semolina, and triticale.

It is a composite compound made up of two main protein groups, the glutenins and the gliadins. Gluten forms the basis for a variety of flour and wheat derived food products consumed throughout the world. Leading scientists have opined that the introduction of gluten-containing grains, which occurred approximately 10,000 years ago when humans transitioned from a hunter-gatherer existence to an agriculture-based one, represents a “mistake of evolution” that created the conditions for many contemporary diseases of civilization.


Gluten sensitivity is a systemic disease with many different manifestations. This disorder is characterized by abnormal immune reactions to ingested gluten.

Celiac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible consequences of gluten sensitivity.

The term gluten sensitivity is really an umbrella concept under which fall three distinct conditions:

  • Celiac enteropathy;
  • Non-celiac gluten intolerance; and
  • A true wheat allergy.

It wasn’t until very recently (actually, March 2011) that doctors and scientists began to shed light on some of the differences between celiac disease and gluten sensitivity (Sapone A, et al. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011 Mar 9;9:23.).

The study included 42 patients with celiac disease (CD), 26 patients with gluten sensitivity (GS), and 39 dyspepsic control (DC) patients with no signs of CD or GS. The researchers tested each participant’s intestinal permeability, gene expression, and immune reactivity.

According to the researchers, one of the key findings of the study is “that celiac disease and gluten sensitivity are distinct clinical entities caused by different intestinal mucosal responses to gluten.”


Celiac disease, also known as gluten-sensitive enteropathy, is an autoimmune disease that affects the small intestine of genetically predisposed individuals causing it to become inflamed when exposed to gluten. The immune system generates an exaggerated response to gluten, begins to mistakenly identify your own normal tissue as a foreign invader (antigen mimicry), and ultimately makes antibodies against your own healthy intestinal tissue.

This leads to the erosion of the villi that line your small intestine with subsequent malabsorption of nutrients and thus malnutrition. Symptoms may include anemia, osteopenia, lactase deficiency, diarrhea, constipation, delayed growth, and weight loss due to malabsorption of nutrients. Other conditions that may also be associated with celiac disease include arthritis, dermatitis, infertility, muscle weakness, and constant fatigue.

Non-Celiac Gluten Sensitivity
Non-celiac gluten sensitivity is often interchanged with gluten intolerance. Gluten sensitivity differs from celiac disease in that the body views gluten as an invader causing a direct immune-inflammatory response (as opposed to antibody formation as seen in celiac disease) both within as well as outside of the digestive tract. Because many of the symptoms of non-celiac gluten sensitivity – such as headaches, lethargy, fatigue, brain fog, mood swings, depression, muscle weakness/disturbances, and joint pain – affect areas outside of your GI system, you may go for years without suspecting you have a gluten intolerance.


Although neurological manifestations (neuropathy, ataxia, seizures, and behavioral changes) of celiac disease have been reported since 1966, it was not until the 1990s that gluten sensitivity was demonstrated in some individuals to show up solely as brain and nervous system dysfunction. Furthermore, the concept of extra-intestinal presentations without enteropathy has only recently become accepted.

We now believe that inflammation such as that which can be caused by gluten sensitivity is at least in part responsible for the dramatic increase in neurodegenerative diseases of civilization: Alzheimer’s, Parkinson’s, depression, MS, and others.


Because this separate and distinct form of gluten sensitivity has only recently been isolated and defined, it can be difficult to diagnose. A very common scenario I encounter in my practice is of someone who has tested negative for celiac disease and wheat allergy but, because definitive testing for non-celiac gluten sensitivity was never done, still suffers from gluten-induced inflammation and disease.

All celiac disease is gluten sensitivity but not all gluten sensitivity is celiac disease. If all we test for is celiac, no wonder so many of us go years with unnecessary inflammation and degeneration.

You do if you have celiac disease or gluten sensitivity.

But before you go gluten-free, there’s something you should do first.


But not just any test will do. I strongly recommend our gold-standard: the Cyrex Array 3 Test from Cyrex Labs. For gluten sensitivity it is the best available on the market. Routine tests for “celiac disease” are not sensitive enough to detect the much more common forms of gluten intolerance.


Sapone A, Lammers KM, Casolaro V, Cammarota M, Giuliano MT, De Rosa M, Stefanile R, Mazzarella G, Tolone C, Russo MI, Esposito P, Ferraraccio F, Cartenì M, Riegler G, de Magistris L, Fasano A. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity. BMC Med. 2011 Mar 9;9:23.

Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D. Gluten sensitivity: from gut to brain. Lancet Neurol. 2010 Mar;9(3):318-30.

Hernandez-Lahoz C, Mauri-Capdevila G, Vega-Villar J, Rodrigo L. [Neurological disorders associated with gluten sensitivity]. Rev Neurol. 2011 Sep 1;53(5):287-300.

Alaedini A, Okamoto H, Briani C, Wollenberg K, Shill HA, Bushara KO, Sander HW, Green PH, Hallett M, Latov N. Immune cross-reactivity in celiac disease: anti-gliadin antibodies bind to neuronal synapsin I. J Immunol. 2007 May 15;178(10):6590-5.

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Meet Dr. Dave

Dr. David Scheiderer MD, MBA, DFAPA, is the Chief Medical Officer and Director of Education for Integrative Psychiatry, Inc. 

An accomplished clinician, educator, and lecturer, Dr. Dave has established himself as a key opinion leader in the fields of both mainstream psychiatry and functional medicine. Dissatisfied with the patient outcomes using only conventional treatments, he began treating his patients by addressing biological imbalances with lifestyle improvements, nutrition and nutraceuticals to get better outcomes. His integrative approach provided much improved results. Dr. Dave is passionate about helping the community he serves by personalizing treatments and educating the public about mental health and healthy aging. He has formulated several of our supplements and sat on the advisory board for many others, ensuring the products we carry are based on science and experience and have the best efficacy rates and highest ingredient quality available.

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