An Evolving Conversation: Implications Beyond Celiac…
Gluten Sensitivity: More Than a Gut Problem
When we think about a reaction to food, we tend to look first at the digestive system. Did it cause bloating? Diarrhea? Constipation? Abdominal pain?
But our relationship with food—and particularly with gluten-containing foods—is not always that simple.
Gluten-related sensitivity can affect much more than digestion. Depending on the condition and the individual, manifestations can involve the whole system — the skin, nervous system, joints, nutritional status and all other areas of health. Many people who experience reproducible symptoms after eating gluten do not have celiac disease or a conventional wheat allergy at all.
This is one reason I think conversations about gluten need more nuance than either “gluten is bad for everyone” or “unless you have celiac disease, gluten can't be bothering you.”
Neither statement accurately reflects what we currently know.
What Exactly Is Gluten?
Gluten is not a single substance. It is a mixture of storage proteins found primarily in wheat, with related proteins present in barley and rye.
One important component of wheat gluten is gliadin.
These proteins are unusually resistant to complete digestion by human gastrointestinal enzymes. As a result, relatively large gluten-derived peptides can remain after digestion. In susceptible individuals—most obviously and extremely demonstrated in celiac disease—those peptides can interact with the intestinal immune system leading to a variety of symptom manifistations.
But what happens next depends tremendously on the person. EVERY BODY IS UNIQUE!
When Gluten Meets the Immune System
Celiac disease provides our clearest understanding of how gluten can trigger an abnormal immune response.
In a genetically susceptible person, gluten-derived peptides are modified by an enzyme called tissue transglutaminase (tTG or TG2). Those peptides can then be presented to immune cells through specific HLA molecules, particularly HLA-DQ2 and HLA-DQ8.
The immune system mounts a response that ultimately creates inflammation and damages the lining of the small intestine.
The villi—the microscopic finger-like projections that provide enormous surface area for nutrient absorption—can become shortened or flattened. This can impair absorption and contribute to problems such as iron deficiency, anemia, bone disease and other nutritional deficiencies.
And importantly, the effects don't necessarily stay in the gut.
Celiac disease is now recognized as a systemic immune-mediated disorder. A person can have neurological, dermatological, musculoskeletal and other manifestations, sometimes with surprisingly little gastrointestinal discomfort.
The Gut Barrier and Immune Activation
The intestinal lining isn't simply a passive tube through which food travels. It is an extraordinarily active interface between the outside environment and the immune system.
The cells lining the intestine are joined by structures called tight junctions, which help regulate what passes across the intestinal barrier.
Research has investigated whether gliadin can influence intestinal permeability through pathways involving the protein zonulin. Gliadin has been shown experimentally to stimulate zonulin-related signaling and alter tight-junction regulation. This area is particularly well studied in celiac disease, while its importance in people without celiac disease remains an active area of investigation.
This distinction is important. Science is ever-evolving in this area and is in early states.
What the research does show us is that interactions among food proteins, the intestinal barrier, microbiota and immune system are considerably more complicated than we once appreciated. And… EVERY BODY IS UNIQUE.
Can an Immune Response to Gluten Affect Other Tissues?
This is where another interesting concept enters the conversation: molecular mimicry and immune cross-reactivity.
Our immune system recognizes particular molecular structures. Sometimes different proteins can contain sufficiently similar structures that an immune response directed toward one antigen can also recognize another.
Researchers have explored whether antibodies associated with gluten responses can cross-react with human tissues. Laboratory research has demonstrated cross-reactivity between some anti-gliadin antibodies and intestinal epithelial antigens, providing biological evidence that this phenomenon can occur.
Autoimmune disease is much more complicated than just a sensitivity to gluten. Genetics, immune regulation, infections, environmental exposures, the microbiome and numerous other factors may all contribute. However, it is still essential to explore the relationship between food/inflammatory food triggers and auto-immune symptom manifestations.
Molecular mimicry is one plausible immunological mechanism being investigated—not a universal explanation for autoimmune disease but a contributing factor necessary to consider.
Gluten-Related Symptoms Can Show Up Almost Anywhere
One of the most important lessons from celiac disease is that the absence of digestive symptoms does not mean the absence of a gluten-related disorder.
Some people experience predominantly gastrointestinal symptoms. Others may experience fatigue, headaches, neurological complaints, joint or muscle discomfort, nutritional deficiencies or skin manifestations.
A striking example is dermatitis herpetiformis, an intensely itchy blistering skin disease caused by gluten-related autoimmunity and considered a manifestation of celiac disease.
Research has also examined relationships between gluten-related disorders and other dermatologic conditions, including psoriasis, eczema, and other inflammatory skin disorders.
But here again, language matters.
An association between two conditions doesn't necessarily mean gluten caused the second condition, nor does it mean everyone with eczema or psoriasis will improve by eliminating gluten.
It does, however, mean that when we're evaluating persistent symptoms, looking beyond the gastrointestinal tract and exploring gluten as a trigger is definitely worthwhile. And… EVERY BODY IS UNIQUE!
Gluten and Autoimmune Disease
There is an important connection between gluten and autoimmunity in general.
Celiac disease itself is an autoimmune disease.
Celiac disease also occurs more frequently in people with certain other autoimmune diseases, including autoimmune thyroid disease and type 1 diabetes.
Researchers continue to investigate relationships among intestinal barrier function, genetic susceptibility, environmental triggers, the microbiome and autoimmune disease.
Inflammatory bowel diseases such as Crohn's Disease and Ulcerative Colitis are distinct diseases from celiac disease. Gluten (although definitely not the only factor) has to be looked at here as a possible (and likely) trigger.
Many people with various inflammatory bowel diseases report improvement in symptoms after eliminating gluten, and dietary interventions are actively studied in IBD. That observation can certainly be useful for us as we are trying to make the body comfortable.
The same caution applies to all other autoimmune disorders.
A gluten-free diet is medically necessary for celiac disease. But we must also look beyond celiac disease and “medical necessary”. When we're trying to make our bodies comfortable through holistic interventions, anecdotal evidence and individual response in symptoms to dietary interventions such as gluten elimination must not be ignored. Therefore, gluten elimination is worth considering in cases of any autoimmune processes.
The take-away message is that individual response is the most important factor to consider. Because… EVERY BODY IS UNIQUE!
What If Celiac Testing Is Negative?
This is where the subject becomes particularly interesting.
There is a recognized condition known as non-celiac gluten sensitivity, increasingly also called non-celiac gluten/wheat sensitivity (NCGWS).
These individuals experience symptoms associated with eating gluten- or wheat-containing foods but do not meet diagnostic criteria for celiac disease or wheat allergy.
And right now, there is no validated laboratory biomarker that definitively diagnoses NCGWS.
That's a very different statement from saying that celiac testing itself is generally inaccurate.
Modern celiac serology—particularly tTG-IgA when used appropriately—is a valuable diagnostic tool. But no test is perfect. IgA deficiency, the amount of gluten being consumed, disease stage and other factors can influence testing.
NCGWS is different. We simply don't yet have a blood test that reliably tells us who has it. BUT WE DON’T NEED ONE!! The most important test result for us is how you feel. Our goal is to make you more comfortable, so that is the only result you and I are going to consider when trying to approach your health holistically. Because… YOUR BODY IS UNIQUE!
And Sometimes It May Not Be Gluten Alone
There is another fascinating complication.
Wheat contains much more than gluten.
It also contains fructans, a type of fermentable carbohydrate belonging to the FODMAP family, as well as proteins called amylase-trypsin inhibitors (ATIs).
Both have been investigated as potential contributors to symptoms attributed to gluten.
Consequently, someone may say, “I feel much better when I stop eating gluten,” and be completely correct about the dietary observation while the biological trigger may actually be gluten, another wheat component, or some combination of them. AND THIS STATEMENT IS THE ONLY ONE WE NEED TO PAY ATTENTION TO!!!
The main take away message is that while our scientific understanding of this area is still evolving, making your feel more comfortable in your body is the only objective data we need.
Why an Elimination Trial is Always Useful
This is where individualized nutrition becomes particularly valuable.
Rather than simply deciding, “I'm gluten intolerant,” the question becomes:
What actually happens to my symptoms when this food is removed, and what happens when it is reintroduced?
That means establishing a baseline and tracking relevant symptoms: digestion, bowel patterns, skin changes, headaches, fatigue, joint discomfort, cognition or whatever complaint prompted the experiment. I always recommend starting with 30-day elimination. However, for some symptoms, particularly skin manifestations, we might need a much longer time period to really explore the full effect/benefit.
After elimination period, the food is deliberately reintroduced.
If symptoms disappear/improve during elimination and reproducibly return with reintroduction, that provides us with actual data about your body and your triggers.
And if nothing changes? Well, that’s useful data too!!
Why Many People Feel Dramatically Better Without Gluten
This is something we shouldn't dismiss simply because the mechanism isn't well understood in laboratories and test tubes.
Many people genuinely report substantial improvements in how they feel after removing gluten-containing foods despite having negative celiac testing.
There are many possible explanations. Some may have NCGWS. Some may be responding to another wheat component. Some may simultaneously reduce highly processed foods or FODMAP intake when they remove wheat. And there are undoubtedly many other mechanisms that science has not completely characterized or even concieved yet.
Current reviews of NCGWS acknowledge that its pathophysiology remains incompletely understood and that a reliable diagnostic biomarker has yet to be identified. BUT WE DON’T NEED ONE!!!! The most reliable diagnostic biomarker we care about is HOW YOU FEEL in your body!
The Goal Isn't to Figure Out Why Gluten is Problematic
There are many reasons why people have challenges digesting gluten and how it can be a trigger for any number of inflammatory/autoimmune symptoms. In holistic approach to health and wellness, we care not about tests, test tubes, molecular explanations, cures, and treatments, etc. The only thing we care about is how to nourish your body in a way that makes you feel comfortable, relieves pain, improves quality of life, and promotes overall long-term wellness.
That's the space where we do our work and where individualized nutrition matters most.
Rather than asking whether gluten is universally good or bad, I think the more useful questions are:
What does my body tell me?
What do my symptoms tell me?
What makes my body feel comfortable?
What happens when we carefully change the variable and observe the response?
Our understanding of gluten, wheat, the intestinal barrier and immune function continues to evolve. There is still much we don't know.
Recognizing what science hasn't answered yet is just as important as understanding what it has. And ultimately, individual experimentation is the most telling piece of data we have (and the only one we need) because… EVERY BODY IS UNIQUE!!!
