Gluten Intolerance? Or Something Else in Wheat?

Part 5 in the Food Sensitivity series

Ever wonder what all the fuss is about with gluten?  Until challenged by lectins, gluten has been the fashionable food to avoid.  Gluten is a protein found in wheat, barley, and rye and high gluten wheat flour is valued for its stretchy characteristics and ability to help bread rise.  But gluten is not the only factor that could be responsible for gastrointestinal distress after eating wheat.  If gluten or wheat bothers your stomach, what could be the cause? 

Decades ago, celiac disease (CD) was the only recognized gluten-related disease, and its prevalence has increased with wheat becoming a dominant food grain worldwide.  CD is a serious autoimmune condition that is controlled only by the avoidance of gluten.  Predisposing factors to developing CD include genetic predisposition, intestinal infections, dysbiosis (predominance of unhealthy gut bacteria), or degraded or thin intestinal mucous layers. 

How gluten causes CD is a complex process, so here is a simplified explanation distilled from my struggles to understand it.  With digestion, gluten is broken down into 2 smaller peptide molecules, gliadin and glutenin.  (It’s unclear if glutenin is problematic, but gliadin’s potential harmfulness is known.)  Normally, gliadin is not able to get past two important lines of defense in the gut: a healthy mucous layer and the tight approximation of the cells of the intestinal lining.

If gliadin penetrates the mucous layer and binds to intestinal cells, it triggers an increase in zonulin.[1]  Zonulin permits loosening of tight junction connections, and the gut lining becomes penetrable.  Gliadin then sneaks between the gut lining cells where it is modified by an enzyme, tissue transglutaminase (tTG), in the gut wall. 

In susceptible individuals with specific genes, the altered gliadin interacts with T immune cells underlying the gut lining to release inflammatory chemicals. This leads to more intestinal lining permeability (“leaky gut”) as well as local, and perhaps bodywide, inflammation.  It also attracts the B immune cells responsible for antibody formation, in this case against both tTG and the modified gliadin.[2] 

Symptoms of celiac disease range from minimal to severe, with diarrhea (usually) or constipation, abdominal pain and bloating, nutritional depletion, and weight loss.  With ongoing inflammation, some individuals may experience a wide array of extra-intestinal issues including headaches, brain fog, fatigue, joint pain, anemia, or other autoimmune disorders.[3]   

Gluten ataxia (GA) with unsteady gait and other neurological symptoms and dermatitis herpetiformis (DH) with its blistery rash are two other gluten-related autoimmune diseases.[4]  Surprisingly, only about 10% of patients with these diagnoses exhibit any GI symptoms. 

Whether or not they suffer from gastrointestinal (GI) symptoms, individuals with CD cannot eat any gluten-containing grain without suffering consequential damage to the small intestinal villi.  These brush-like projections of the intestinal lining flatten out resulting in poor nutrient absorption.  Recovery from an exposure to wheat, barley, or rye takes several weeks to months.

Due to the significant immune component of this disease, complete avoidance of gluten-containing foods is necessary.  This entails lots of label reading and careful instructions in restaurants if the patient eats out at all.

Food additives are a stumbling block to being gluten-free.  Wheat is unexpectedly found in many condiments and highly processed foods. For instance, some modified food starches are extracted from wheat.  Moreover, certain additives are considered “processing agents” by the FDA for which there are no specifications as to labeling.  One compound, called microbial transglutaminase (mTG), is chemically like tTG.  Microbial TG is used in many food products from meats to dairy to baked goods (even gluten-free!) and there is evidence for it causing GI symptoms in those with CD.[5]  Nicknamed “meat glue,” mTG is used widely in the food industry to stick small pieces of meat, poultry, or seafood together to form “reconstructed” or “formed” products like nuggets, steaks, meatballs, lunchmeats, and imitation crab.

Not everyone with discomfort after eating wheat has CD. Non-celiac gluten sensitivity (NCGS) is an intolerance to wheat (and maybe barley and rye) when tests for both celiac disease and wheat allergy are negative.  It is a poorly understood condition and perhaps gliadin or other gluten-related peptides have other undetermined mechanisms to cause GI distress. 

Or maybe it’s not gluten, but something else in wheat that is problematic.  Other wheat-related instigators include Wheat Germ Agglutinin (WGA), Amylase-Trypsin enzyme Inhibitors (ATI), and fructans, a FODMAP.[6]   

WGA and ATI (both proteins)—but not fructans—can cause increased intestinal permeability, gut wall inflammation, and perhaps, immune ramifications in susceptible individuals.  Unlike in CD, the villi remain intact.  Symptoms include GI distress and sometimes generalized symptoms of headache, “brain fog,” fatigue, and skin or joint irritation.  While gliadin, WGA, and ATI are the most notorious culprits, there may be other wheat proteins not yet identified that are troublesome.

Unlike the protein-based causes, fructans generally cause only intestinal distress with GI bloating and loose stools.  The distension, however, may negatively impact the gut’s nervous system and indirectly affect mood via the gut-brain axis.

There is another suspect to consider if one eats non-organic wheat—glyphosate.  Glyphosate is an herbicide that is used as a pre-harvest treatment by large growers of wheat and other grains.  While the herbicide is touted as safe for humans, it not only kills broadleaf plants (weeds), but also many bacteria.  Residual glyphosate in grain is linked to detrimental effects on our healthy gut bacteria which can lead to a dysbiotic imbalance favoring unhealthy gut bacteria, degraded mucous, and, likely, GI distress.[7]

As you can see, pinpointing the cause of one’s intolerance to wheat is complicated. Gluten, other wheat-related proteins like WGA and ATI, and the FODMAP, fructan, are frequent suspects.  Not often discussed, but additives or residual glyphosate present in gluten-containing foods may also play a role.  (More on these latter two topics to come.)  There may also be overlap of symptoms from other food intolerances coinciding with the ingestion of grain—for instance, sauces or toppings found on pizza or pasta.  Keeping a food diary may help define relationships between foods and symptoms.  Details regarding brand names of processed foods might provide clues if suspected additives are on an ingredient list.

So, what can you do if you suspect a wheat-related food sensitivity?  If wheat or gluten-containing foods (wheat, barley and rye) consistently cause GI discomfort, see a doctor.  The most serious diagnoses, CD and wheat allergy will be ruled out first.  Testing should be done while still eating the suspected foods and individuals on gluten-free diets will be asked to eat a minimum amount of gluten-containing foods for 2 weeks prior to testing.

 Sadly, most therapies involve wheat-free or gluten-free diets.  This means more than giving up bread, pasta, and cereal but also removing highly processed foods with extraneous wheat-based ingredients and additives from one’s diet.  Preparing meals “from scratch” might allow for more control if condiments are properly vetted.  Organic foods are grown and prepared without pesticides and unexpected “processing” agents, but may contain some wheat-based ingredients, so label reading is still imperative.

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[1] Alessio Fasano, “Zonulin, Regulation of Tight Junctions, and Autoimmune Diseases,” Annals of the New York Academy of Sciences 1258, no. 1 (July 2012): 25–33, https://doi.org/10.1111/j.1749-6632.2012.06538.x.

[2] Giacomo Caio et al., “Celiac Disease: A Comprehensive Current Review,” BMC Medicine 17 (July 23, 2019): 142, https://doi.org/10.1186/s12916-019-1380-z.

[3] Amelie Therrien, Ciaran P. Kelly, and Jocelyn A. Silvester, “Celiac Disease: Extraintestinal Manifestations and Associated Conditions,” Journal of Clinical Gastroenterology 54, no. 1 (January 2020): 8–21, https://doi.org/10.1097/MCG.0000000000001267.

[4] Anna Sapone et al., “Spectrum of Gluten-Related Disorders: Consensus on New Nomenclature and Classification,” BMC Medicine 10 (February 7, 2012): 13, https://doi.org/10.1186/1741-7015-10-13.

[5] Aaron Lerner and Torsten Matthias, “Processed Food Additive Microbial Transglutaminase and Its Cross-Linked Gliadin Complexes Are Potential Public Health Concerns in Celiac Disease,” International Journal of Molecular Sciences 21, no. 3 (February 8, 2020): 1127, https://doi.org/10.3390/ijms21031127.

[6] Maria Gloria Mumolo et al., “Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity?,” Nutrients 12, no. 12 (December 10, 2020): E3785, https://doi.org/10.3390/nu12123785.

[7] Jacqueline A. Barnett and Deanna L. Gibson, “Separating the Empirical Wheat From the Pseudoscientific Chaff: A Critical Review of the Literature Surrounding Glyphosate, Dysbiosis and Wheat-Sensitivity,” Frontiers in Microbiology 11 (2020), https://www.frontiersin.org/article/10.3389/fmicb.2020.556729.