Fix Your Gut Podcast #7 – Celiac Disease, Gluten, and Grains

Most people love to eat bread. Nothing is better than the smell of a fresh loaf of bread baking in the oven. Who does not miss eating a delicious hot slice of pizza if you have given up gluten? Occasionally, if your gastrointestinal system is in optimal shape, eating a slice of bread or pizza now and then might not hurt you. But for a lot of people with gastrointestinal issues, continuous or even acute consumption of gluten does damage to their digestive tract.

What is Gluten?

Gluten is a binding protein that is found in wheat and other related grain species such as barley and rye. Gluten is what gives elasticity to dough and helps wheat products rise, keep its shape, and is what gives wheat its chewy texture.¹ Gluten is the composite of two other proteins, gliadin and glutenin, which are eighty percent of the protein in wheat. Gluten is not destroyed by cooking or processing is present in all wheat products.²

Gluten is in almost every meal the average American consumes. Make sure you always check nutrition and ingredient labels. If you eat out for your meals, check the restaurant’s ingredient list before dining. Gluten is found in bread; most cereals, cookies, muffins, pancakes, waffles, most fried foods are coated in wheat flour, pies, cakes, gravy, pizza, pasta, wheat flour tortillas, and other foods made with wheat flour. Remember, your food can be contaminated with gluten if it is fried in the same oil as food that contains gluten (like fries that are fried in the same oil that onion rings are fried in). Gluten can even be added to food secretly, like McDonald’s French fries, where it is added as a natural flavoring. Finally, gluten proteins are not destroyed by cooking, heating, or cooling in any food product.³

So why are gluten intolerance and celiac disease on the rise in most industrialized countries? I believe the leading causes of the increase in these conditions are because of the increased use of the herbicide glyphosate, iron fortification of wheat products, and modern wheat farming methods that contain higher gluten from shorter growing cycles to increase crop yields.

What Might be the Reasons Celiac Disease and Gluten Sensitivity is on the Rise?

Glyphosate has been strongly linked with the increase in celiac disease diagnosis which might (with iron fortification) explain the French paradox. The French paradox is that the French despite eating large amounts of gluten, cheese, and consuming a lot of wine have some of the lowest levels of cardiovascular disease and celiac disease in the industrialized world. Finland has some of the highest rates of celiac disease in Europe and Finland regularly sprays glyphosate on its wheat fields (like we do in America) and fortifies its wheat products with iron. France, on the other hand, sprays fewer amounts if any at all on the soil where the wheat is grown and rarely fortifies their flour with iron.^{4 5 6 7}

Glyphosate is an organophosphorus herbicide that was brought to the market by Monsanto in the 1970’s as Roundup. Glyphosate is the most used herbicide on farms throughout the United States and is frequently used for commercial applications and by homeowners as well. Monsanto, the FDA (Food and Drug Administration), EPA (Environmental Protection Agency), and the USDA (United States Department of Agriculture) all claim that glyphosate is 100% safe. In the middle 1990’s Monsanto produced ads that Roundup was “safer than table salt” and “practically nontoxic” to mammals, which later the attorney general of New York, Dennis C. Vacco ordered the ads to be removed. Monsanto later claimed that the phrases in question were permissible under the EPA guidelines and that glyphosate is safe. Glyphosate is absorbed by foliage and less by its roots of plants. Therefore, it is only useful with grown plants and not seeds. Glyphosate inhibits the plant’s synthesis of the amino acids phenylalanine, tyrosine, and tryptophan in the shikimate pathway by inhibiting the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSP) causing the plants not to produce proteins that are essential for growth and survival. The shikimate pathway is also used by bacteria, fungi, algae, and some protozoan parasites to biosynthesize folates and the above listed aromatic amino acids. Glyphosate is supposed to be safe for humans because we do not rely on the shikimate pathway to synthesize amino acids, instead, like most animals, we must consume the above listed essential amino acids in our diet for survival. Some genetically engineered crops are resistant to glyphosate, and some plants are now becoming resistant to glyphosate as well as developing extra copies of the ESPSS gene, which encodes the EPSP enzyme.^{8 9}

Glyphosate does interfere with some bacteria, yeast, and parasites in our microbiome (through inhibiting the shikimate pathway), both probiotic and opportunistic microbes. Since Bifidobacteria and Lactobacillus make up a large part of our probiotic microbiome in our gut and are affected by glyphosate, ingesting glyphosate even in minute amounts in our drinking water or pesticide residue on our food is probably not a good idea. Bifidobacteria and Lactobacillus are also crucial in maintaining a proper gut barrier and help to digest the wheat we consume. In mammals, glyphosate has been shown to interfere with cytochrome P450 pathway and liver function which are essential for detoxification and digestion. People with celiac disease are known to suffer from fat metabolism and issues with liver, gallbladder, and pancreatic health. CYP enzymes are crucial in the production of bile by the liver which can reduce in people who ingest too much of the herbicide which may lead to reduced fat digestion, dysbiosis, leaky gut, and celiac disease. The enzyme CYP27A is identical to the mitochondrial vitamin D activating enzyme, which might explain why 64% of men and 71% of women with celiac disease were found to be vitamin D deficient. Finally, glyphosate may cause issues with sulfur metabolism, glutathione depletion, and molybdenum cellular depletion.^{10 11}

“In (Samsel and Seneff, 2013), a hypothesis was developed that glyphosate disrupts the transport of sulfate from the gut to the liver and pancreas, due to its competition as a similarly kosmotropic solute that also increases blood viscosity. (Kosmotropes are ions that induce “structure ordering” and “salting out” of suspended particles in colloids). Insufficient sulfate supply to the liver is a simple explanation for reduced bile acid production. The problem is compounded by impaired CYP enzymatic action and impaired cycling of bile acids through defective enterocytes in the upper small intestine. The catastrophic effect of loss of bile acids to the feces due to impaired reuptake compels the liver to adopt a conservative approach of significantly reduced bile acid synthesis, which, in turn, leads to gall bladder disease. While H2S is well known as a toxic gas through its inhibition of aerobic respiration, a recent paradigm shift in the research surrounding H2S has been inspired by the realization that it is an important signaling gas in the vasculature, on par with nitric oxide (Li et al., 2011). H2S can serve as an inorganic source of energy to mammalian cells (Módis et al., 2013). 3-mercaptopyruvate sulfurtransferae (3MST) is expressed in the vascular endothelium, and it produces H2S from mercaptopyruvate, an intermediary in the breakdown of cysteine (Kimura, 2011). Endogenously produced H2S derived from 3-mercaptopyruvate stimulates additional mitochondrial H2S production, which then is oxidized to thiosulfate via at least three different pathways (Ingenbleek and Kimura, 2013; Hildebrandt and Grieshaber, 2008; Goubern et al., 2007), producing ATP. The inflammatory agent superoxide can act as substrate for the oxidation of H2S to sulfite and subsequently sulfate and the activated form, PAPS (Seneff et al., 2012), but will likely induce oxidative damage in the pancreas, particularly, as we will see in section 7, if molybdenum deficiency impairs sulfite-to-sulfate synthesis. Pancreatic beta cells express extraordinarily high levels of heparan sulfate, which is essential for their survival (Ziolkowski et al., 2012), since it protects them from ROS-induced cell death. Because sulfate transport via the hepatic portal vein is likely disrupted by glyphosate, H2S, whether derived from sulfur-containing amino acids or supplied via diffusion following its production by sulfur-reducing bacteria in the gut, can become an important source of sulfur for subsequent sulfate production locally in the pancreatic cells. Pancreatic elastase is a serine protease that is needed to assist in protein degradation, but an overabundance can lead to autolysis of tissues (Ito et al., 1998). Cholesterol sulfate inhibits pancreatic elastase (Ito et al., 1998), so a deficiency in cholesterol sulfate supply due to impaired sulfate supply to the liver and impaired CYP function should increase the risk of tissue digestion by pancreatic enzymes, contributing to the loss of villi in the upper small intestine observed in celiac disease.”¹²

Finally, glyphosate can lead to retention of retinoic acid which is an important regulator of intestinal immunity. “In celiac disease, T cells develop antibody responses against dietary gluten, a protein present in wheat (Jabri & Sollid, 2009). RA, a metabolite of vitamin A, has been shown to play a critical role in the induction of intestinal regulatory responses (Mora et al., 2008; Coombes et al., 2007; Mucida et al., 2007). The peptide in gluten, A-gliadin p31-43, induces interleukin 15 (IL-15), a key cytokine promoting T-cell activation (Hershko & Patz, 2008). RA synergizes with high levels of IL-15 to promote JNK phosphorylation (Nanda, 2011; DePaolo et al., 2011), which potentiates cellular apoptosis (Putcha et al., 2003). IL-15 is a causative factor driving the differentiation of precursor cells into anti-gluten CD4+ and CD8+ Th1 cells in the intestinal mucosa. Furthermore, in (DePaolo et al., 2011), it was discovered that RA exhibits an unanticipated co-adjuvant property to induce Th1 immunity to antigens during infection of the intestinal mucosa with pathogens. Retinoic acid has also been shown to directly suppress transglutaminase activity, another way in which it would negatively impact celiac disease (Thacher et al., 1985). Thus, it is becoming clear that excess exposure to RA would increase risk to celiac disease, and warnings have been issued regarding potential adverse effects of RA supplements on celiac disease. A possible mechanism by which glyphosate might induce excess RA is via its interference with the CYP enzymes that metabolize RA. There are at least three known CYPs (CYP26A1, CYP26B1 and CYP26C1) that catabolize RA, and they are active in both the embryo and the adult (Taimi et al., 2004). A 1/5000 dilution of glyphosate was sufficient to induce reproducible malformations characteristic of RA exposure in frog embryos (Paganelli et al., 2010).” Accutane (13-cis-retinoic acid) has been linked to bowel inflammatory issues, so you would believe that it would also have a link to celiac disease by increasing immune reactions to gluten within the gut. One study concludes that Accutane does not cause celiac, but more tests need to be performed in my opinion because of possible outside influence, “This study was funded by the National Institutes of Health, grant number DK057982 (Dr. Murray) and the Mayo Clinic.”^{13 14 15}.

There is much concern over the fortification of elemental iron added to our food and how it affects our gut health. The type of iron that is used for supplement and added to our meals is nonheme iron, most of the time it is not even a proper iron chelation. The iron found in most fortified cereal products are ferrous and ferric and can be magnetized. The iron that we ingest from meat is heme bounded (iron that we can absorb), and iron from plants is bounded to phytic acid (iron that has to be broken down by our microbiome), we do not ingest large amounts of unbounded iron in our diet. Iron can affect the microbiome, mucosal, and immunological integrity of the gastrointestinal tract leading to dysbiosis and leaky gut. Most organisms in the gut use iron for metabolism and if you are suffering from dysbiosis giving the organisms iron can lead to increase colony growth and virulence. Ingestion of unbonded iron can also increase inflammation in the gastrointestinal tract and has been linked to gastrointestinal upset, increased lipid peroxidation, intestinal cancer, and constipation. Iron regulation by the body is essential to prevent against dysbiosis and inflammation.^{16 17 18 19}

“The gut microbial community thrives on complex carbohydrates and proteins that are not digested and taken up by the upper intestine. The balanced community also depends on the provision of micronutrients for metabolism and replication. There is a continuous competition for these nutrients, which is reflected in the different requirements and uptake mechanisms that certain species possess. Metabolic competition and interactions are also ways in which the gut microbiota restrains the growth of unwanted pathogens (Kamada et al., 2013). One of the micronutrients that the vast majority of bacterial species require for their growth and metabolism is iron (Andrews et al., 2003). However, in the human body, iron availability to microorganisms is generally extremely limited, due to innate iron withholding mechanisms that aim to prevent growth of pathogenic invaders (Cassat & Skaar, 2013). Such a tightly regulated system of nutritional immunity is not known for the lumen of human gut. However, also in the gut lumen with high amounts of dietary iron present, gut microorganisms have to deal with the stress of iron limitation as the presence of freely available ‘unbound’ iron is probably limited due to the environmental conditions of the colon lumen. The balance of bound and unbound iron can be (re)disturbed by the oral administration of supplementary iron, a common strategy to treat iron deficiency, which is known to cause alterations of the gut microbiota composition and metabolism.”²⁰

Gluten Intolerance and celiac disease are becoming more prevalent all over the world because wheat was selectively bred in the 1960s to contain more gluten and gliadin. These new wheat plants were shorter and were quicker to harvest. The extra gluten and thicker gluten strands support higher grain yields. You can still purchase Einkorn wheat (heirloom wheat) which has less gluten and gliadin than modern wheat. Einkorn wheat tends to cause less of a reaction in your average person if they are sensitive to wheat (people with celiac disease still have to avoid it.)²¹

Upon digestion, gliadin is reduced to a collection of five polypeptides, which bind to the opiate receptors of the brain, which makes eating wheat addictive. It also stimulates appetite and leads to wheat cravings. Gliadin also has been shown to increase small intestinal permeability leading to leaky gut syndrome. Finally, giladin resembles some of the thyroid hormones in the body closely and may hinder optimal thyroid function and in some people cause hypothyroidism.^{22 23}

Glutenin has been shown to bind to the leptin receptor in your stomach causing hunger, which leads to less leptin being produced and circulating throughout the body. Leptin is the hormone of satiety, and it is what makes you feel full after eating a meal. Ingestion of glutenin makes you crave more food and often leads to overeating.²⁴

I know that you were taught to believe that whole wheat bread is better for you than standard white bread. The problem with whole wheat bread is that it contains more gluten and more amylopectin A which is the “complex” carbohydrate unique to wheat that is highly digestible by the enzyme amylase in your saliva and pancreatic secretions. Since amylopectin A is a carbohydrate that is easily digested, it causes elevated blood glucose levels. After eating, two slices of whole wheat bread, your blood glucose increases more than eating two tablespoons of sugar.²⁵

These are the issues I have with the everyday consumption of wheat for most people. Modern wheat can be very difficult to digest, and most people with gut issues might be better off avoiding it. If you do ingest wheat, I would recommend using unfortified organic einkorn flour or wheat products or use organic French unfortified flour or wheat products if possible. Making a long-term sourdough fermented bread (one month at least) might reduce gluten to nondetectable levels, and when made with the recommend flours might be safe to eat. Some people with gluten intolerance or rarely celiac disease might be able to tolerate these forms of wheat. Hopefully, one-day glyphosate and fortification will be banned from our food supply so people can finally enjoy their meals without them causing as much if any at all digestive discomfort.