What is gluten intolerance?
The phrase “gluten intolerance” is an all-encompassing description of the health issues that arise from eating gluten, a protein found in wheat, barley and rye. It may actually be a misnomer, because researchers are finding that other components of these grains could be responsible for symptoms, alone or in conjunction with gluten. So how do we define gluten intolerance, and what are the other components in wheat that could be causing problems?
Gluten intolerance vs celiac
In celiac disease, the body’s adaptive immune system attacks intestinal cells in reaction to gluten. Those with celiac have one or both of two genes, called HLA-DQ2 and HLA-DQ8, that code for a protein on immune cells that causes them to make antibodies against gluten and an enzyme produced in intestinal cells called tissue transglutaminase (tTG). Exactly how it causes damage isn’t clear, but the result is intestinal lesions, scarring and flattening of the villi – folds in the intestinal lining that create more surface area for nutrient absorption. This can cause significant malabsorption if untreated, and result in conditions like osteoporosis from inadequate calcium and vitamin D, anemia from inadequate iron, B12 and folic acid, chronic diarrhea and weight loss. Celiac is diagnosed by genetic testing for the HLA-DQ2/8 genes, intestinal biopsy that shows lesions and flattening of villi, and/or blood testing that shows anti-tTG antibodies. Currently, the only treatment for celiac is complete avoidance of gluten, although drug treatments and other methods are being developed.
Gluten intolerance separate from celiac or wheat allergy is non-celiac gluten sensitivity/wheat sensitivity, or NCGS/WS. It’s a long acronym, but accurate to describe that both gluten and other aspects of wheat are involved in symptoms attributed to wheat consumption. As its name implies, it refers to having a sensitivity to wheat or gluten, without the severe lesions, flattening of intestinal villi or antibodies against tTG found in celiac. Not all the mechanisms that cause sensitivity are yet known, but interestingly 50% of those with HLA-DQ2/8 genes have NCGS/WS, as opposed to 30% of the general population, and those with family members who have celiac are more likely to develop NCGS/WS, implying a genetic component. We do know that dysbiosis, inflammation, dysregulation of tight junctions between intestinal cells and impaired nutrient absorption cause symptoms like abdominal pains, eczema/rash, headache, brain fog, fatigue, diarrhea, depression, anemia, sore joints, brittle nails, thinning hair and dull or acneic skin. The only way to diagnose NCGS/WS is if celiac and wheat allergy are ruled out via genetic or blood tests or biopsy, but symptoms alleviate with removal of gluten or wheat from the diet.
So, all celiacs are gluten intolerant, but you can be sensitive to gluten or wheat but not celiac.
Can you be okay with gluten but not wheat?
We know that celiac is directly caused by gluten, and gluten, because it isn’t fully broken down by human digestive enzymes, causes tight junctions to open when they shouldn’t and stay open for too long. This leads to inflammation, and can cause gut microbial imbalances, but other substances in wheat like FODMAPs, amylase-trypsin inhibitors (ATIs) and lipopolysaccharides (LPS) could also be culprits in NCGS/WS.
Is it FODMAPs or gluten?
The term FODMAP is an acronym for fermentable oligosaccharides, disaccharides and monosaccharides and polyols. They are simple sugars like cane sugar (sucrose), milk sugar (lactose) or fruit sugar (fructose), short-chain carbohydrates of up to 10 linked sugars like fructans (FOS) and galacto-oligosaccharides (GOS) and indigestible sugar alcohols like mannitol, xylitol and sorbitol. Fermentable means they aren’t being well-absorbed, and make it to the large intestine where they’re eaten by an overgrowth of certain gut microbes. Too many simple sugars in the gut can pull in water from the body via osmosis and cause diarrhea, and gut microbes giving off gas as a byproduct of feasting on the sugars can cause bloating and pain.
Wheat contains low-to-moderate amounts of FOS, but can be problematic for those with FODMAPs intolerance because it’s so prevalent in the Western Diet. Those with gluten intolerance may also have issues with FODMAPS due to the impaired absorption and dysbiosis that gluten causes, but many people with NCGS/WS can tolerate other sources of FODMAPs when on the gluten-free diet (GFD), indicating the problem started with gluten or other wheat components. FODMAPs reactions also don’t account for the inflammation seen in those with NCGS/WS (Leccioli et al., 2017). However, those who see only partial resolution of GI symptoms on a healthy, whole-foods GFD and still have problems with high-FODMAP foods like onions, garlic and certain fruits may actually be FODMAPs intolerant (Catassi et al., 2013).
Is it ATIs or gluten?
Amylase-trypsin inhibitors (ATIs) are water-soluble proteins in wheat that, like gluten, are not completely broken down by human digestive enzymes. Studies show that they attach to receptors on immune cells in the gut, resulting in release of inflammatory cytokines. Their function in wheat is to protect against insects and parasites, and interestingly, they’re found in lower amounts or none at all in ancient strains of wheat, which could partly account for the rise in wheat intolerance in modern times. Gluten-containing grains have particular types of ATIs, while other grains and gluten-free products have less-complex ATIs that are better broken down during digestion and don’t stimulate as much of an immune response. It’s likely that wheat ATIs worsen chronic inflammation caused by gluten, after gluten opens tight junctions between cells and allows intestinal contents to contact immune cells in the tissues below (Zevallos et al., 2017).
So while ATIs may be a problem, the most problematic of them always come with gluten, and the two work together, along with other factors like dysbiosis, to promote an inflammatory response.
Are there other components in wheat that cause symptoms?
Lipopolysaccharides (LPS) are components of gram-negative bacterial cell walls that are shed or left behind when the bacteria dies. They can trigger inflammation in the same way as ATIs, and increase tight junction permeability. Intestinal cells produce an enzyme called intestinal alkaline phosphatase (IAP) that transforms LPS so they can’t attach to inflammatory receptors, but when intestinal cells are compromised by chronic inflammation seen in NCGS/WS (Uhde et al., 2016), it impairs IAP production. NCGS/WS is characterized by a reduction in gram-positive Firmicutes bacteria, allowing for an increase in gram-negative bacteria. These factors can allow LPS to trigger intestinal inflammation and enter the bloodstream, causing systemic inflammation (Salguero et al., 2019).
The bottom line
Ultimately, it doesn’t matter what exactly is triggering your symptoms if you’re intolerant to wheat, the root of the problem is weakened digestion, dysfunctional absorption and dysbiosis, and the solution is to restore your gut health. Alimental’s Gut Restoration Program includes six steps to address all these issues and more. Check it out here.
References
Leccioli, V., Oliveri, M., Romeo, M., Berretta, M., & Rossi, P. (2017). A new proposal for the pathogenic mechanism of non-coeliac/non-allergic gluten/wheat sensitivity: Piecing together the puzzle of recent scientific evidence. Nutrients, 9(11), 1203. https://doi.org/10.3390/nu9111203
Catassi, C., Bai, J. C., Bonaz, B., Bouma, G., Calabrò, A., Carroccio, A., Castillejo, G., Ciacci, C., Cristofori, F., Dolinsek, J., Francavilla, R., Elli, L., Green, P., Holtmeier, W., Koehler, P., Koletzko, S., Meinhold, C., Sanders, D., Schumann, M., Schuppan, D., … Fasano, A. (2013). Non-celiac gluten sensitivity: The new frontier of gluten related disorders. Nutrients, 5(10), 3839–3853. https://doi.org/10.3390/nu5103839
Zevallos, V. F., Raker, V., Tenzer, S., Jimenez-Calvente, C., Ashfaq-Khan, M., Rüssel, N., Pickert, G., Schild, H., Steinbrink, K., & Schuppan, D. (2017). Nutritional wheat amylase-trypsin inhibitors promote intestinal inflammation via activation of myeloid cells. Gastroenterology, 152(5), 1100–1113.e12. https://doi.org/10.1053/j.gastro.2016.12.006
Uhde, M., Ajamian, M., Caio, G., De Giorgio, R., Indart, A., Green, P. H., Verna, E. C., Volta, U., & Alaedini, A. (2016). Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut, 65(12), 1930–1937. https://doi.org/10.1136/gutjnl-2016-311964
Salguero, M. V., Al-Obaide, M. A. I., Singh, R., Siepmann, T., & Vasylyeva, T. L. (2019). Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Experimental and therapeutic medicine, 18(5), 3461–3469. https://doi.org/10.3892/etm.2019.7943
