Unraveling the Gluten Mystery: Is Glyphosate the Hidden Culprit?

Gluten, a protein found in wheat, rye, and barley, has nourished human health for thousands of years, and yet over the last few decades, this quintessential staple in many diets seems to be causing havoc on our digestive and immune systems. More and more people across the globe are choosing a gluten-free diet, whether as a proactive lifestyle choice or after a diagnosis of potentially life-threatening celiac disease. Researchers have begun to question if the most important causal factor behind the rising instances of gluten sensitivity is modern wheat, or if glyphosate, a ubiquitous herbicide used in agricultural practices, is the pathway to modern diseases.

Let's explore how gluten acts as an autoimmune trigger in celiac disease, the potential connections between gluten, glyphosate exposure, and non-celiac gluten sensitivity, and the growing ties between the effects of glyphosate residues on the gut microbiome and overall human health.

Celiac disease and gluten

Before we investigate the potential health implications of glyphosate exposure on the development of gluten intolerance and an imbalance of the gut microbiome (dysbiosis), let's briefly look into gluten and the development of celiac disease.

What is gluten?

Proteins are made of chains of peptides (a small sequence of amino acids) and amino acids (smallest protein units). Different types of amino acids — proline, phenylalanine, tryptophan, etc — join together in varying sequences to form thousands of proteins. Gluten is a protein network composed of two main proteins: gliadin, and glutenin, which are found in rye, wheat, barley, and triticale (a hybrid of wheat and rye). 

Gliadin belongs to the prolamin protein group due to its high proline (amino acid) content. This is a significant distinction since gliadin and other prolamine proteins are partially resistant to digestion by human digestive enzymes1. 

To understand gluten intolerance better, it is important to examine the role of gliadin in gluten formation and how protein degradation works in the body.

Developing gluten and its uses

When wheat is ground into flour, mixed with water and kneaded, gliadin, and glutenin form a protein matrix (gluten), resulting in the development of a stretchy and elastic network that is effective in trapping air during bread fermentation, resulting in a variety of breads. 

Commercially, the binding (emulsifying) and thickening capacity of gluten along with its neutral flavor make it a useful addition in packaged foods like soups, sauces, protein mixes (as a way to increase protein content), crackers, etc.

Gliadin and protein degradation in the gut

Gliadin and glutenin are made up of peptides (smaller sequences of amino acids that join together to form proteins). There are different types of gliadin (α, β, γ, and ω) and each type can interact differently with the digestive system. As mentioned before, prolamine proteins like gliadin are partially resistant to degradation by human proteolytic (protein degrading) enzymes. 

Amino acids hold onto each other with the help of bonds to form stable and unique structures. Gliadin has high levels of proline and glutamine residues which contribute to a highly stable and tightly bound structure that is difficult to access for the human digestive enzymes. It is important to note that despite gliadin being resistant to complete breakdown by the human digestive enzymes, it can be broken down by beneficial bacteria8 like B. subtilis, B. longum, and P. acidilactici amongst others.

Complete protein degradation results in amino acids circulating through the body for body growth, repair, and recovery. But incomplete gliadin digestion can result in relatively large chunks of gliadin peptides1 that may trigger the immune system in genetically susceptible populations, who, under additional environmental stress18 (potentially including the timeframe of early life wheat exposure, type of wheat /gluten, early life feeding patterns, gut microbiome diversity, early life infections and immune systems response), can develop1 celiac disease, an autoimmune condition.

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Role of gliadin as an autoimmune trigger in celiac disease

Celiac disease is an autoimmune response to toxic gliadin peptides that damage the gut wall and malabsorption of essential nutrients2. Let's look at the composition of the gut wall to understand how gliadin peptides trigger the immune system.

Gut permeability and zonulin

Think of your gut as a hollow tube consisting of several layers, starting from the innermost layers and outwards, it contains an inner and outer mucus layer, lined by a single layer of intestinal epithelial cells and the lamina propria, which is a thin layer of connective tissue containing immune cells, blood vessels, and lymphatic vessels.

Intestinal epithelial cells are held together by mortar-like proteins known as tight junctions that help maintain the gut barrier function. During nutrient absorption, tight junctions ease up and allow nutrients to pass through the epithelial barrier and into the lamina propria for further circulation.

Zonulin is a protein synthesized in the liver that signals tight junctions to open up, increasing intestinal permeability. Zonulin-led intestinal permeability can increase in response to nutritional, environmental, and bacterial cues3.

Zonulin, gut permeability, and celiac disease

In celiac disease, certain parts of gluten (called gliadin peptides) aren't fully digested, which leads4 to the release of a protein called zonulin. Zonulin makes the intestine more "leaky," allowing these undigested gluten pieces to come into contact with an enzyme called tissue transglutaminase (tTG). This interaction changes the gluten fragments into a form that triggers the immune system into launching an inflammatory response and damaging the intestines.

If someone with celiac disease keeps eating gluten, it causes chronic inflammation and damages the cells that line the intestines. This can result in something called villous atrophy, where the tiny, finger-like projections (villi) in the small intestine flatten out and can no longer absorb nutrients properly. This damage can lead to nutritional deficiencies5, such as low iron or vitamins.

Celiac disease can also lead to other health issues, like thyroid problems6, type 1 diabetes6, or an increased risk of a certain type of cancer (non-Hodgkin's lymphoma)7.

The main treatment for celiac disease is to avoid gluten for life, which helps control symptoms and allows the gut to heal. There is also growing interest in developing8 enzyme-based therapies that could help break down gluten in people with celiac disease.

Learn about molecular mimicry, microbial, and dietary autoimmune triggers in the development of Parkinson’s disease!

Gluten sensitivity, gluten intolerance, non-celiac wheat sensitivity, and wheat allergy --- Is it all the same?

Wheat allergy is an immediate allergic response to wheat. Consuming foods that contain wheat or wheat flour inhalation can result in difficulty in breathing, swelling of the mouth and throat, itching, hives, a rapid heartbeat, a drop in blood pressure, and anaphylaxis9. 

Wheat intolerance, gluten intolerance, gluten sensitivity, and non-celiac gluten sensitivity (NCGS) all refer to digestive symptoms like brain fog, abdominal bloating and pain, diarrhea, nausea, aphthous stomatitis (recurring mouth ulcers, also known as canker sores), irregular bowel movements, and constipation upon gluten ingestion9.

Cereal grains including wheat are often contaminated with mycotoxins (toxins produced by mold or fungi growing on them) that can lead to long-term health effects. Researchers are now exploring the potential role of foodborne mycotoxins on the development of various diseases including autism spectrum disorder and Alzheimer’s disease.

Individuals self-report9 that avoiding wheat-based foods leads to improved digestive health, reduced inflammation, reduced joint pain, and improved mental health benefits.

Glyphosate, glyphosate-based herbicides, and effects of glyphosate exposure on gut health

Glyphosate, the active ingredient in popular herbicides like RoundUp, is one of the most widely used chemicals in agriculture. These glyphosate-based herbicides (GBHs) are designed to control weeds but come in various formulations with additional ingredients, such as polyoxyethylene amine (POEA), which may contribute10 to even more harmful effects on human health.

Beyond weed control, glyphosate is also used in farming as a pre-harvest treatment to speed up the drying process of crops like grains and legumes. This process, called crop desiccation, allows for more uniform drying of the crop while it's still in the field, making mechanical harvesting easier, faster, and less costly. In crops like sugarcane, glyphosate is applied to increase sucrose content by acting as a ripening agent. There are now more than 60 crops that use this pre-harvest application adding to increased glyphosate residues in the food supply. 

So, how exactly does glyphosate work?

Shikimate Pathway -  Why is it important for us?

The shikimate pathway is a crucial biological process found in plants, bacteria, and fungi, but not in animals or humans. This pathway produces essential aromatic amino acids that are not only used to build proteins but also lead to the production of important secondary compounds that help plants defend themselves and grow.

Since humans and animals rely on plants and microbes to supply these amino acids through their diet, any disruption in this chain would have significant consequences for our health and survival. Without these amino acids, key biological processes in humans and animals, such as protein synthesis and the production of essential compounds, would be compromised. This highlights just how vital the shikimate pathway is to the entire ecosystem, even though we don’t have it ourselves, we rely on it for our survival.

How does glyphosate disrupt the shikimate pathway?

Glyphosate works by blocking the shikimate pathway. This pathway helps convert carbohydrates into essential compounds needed for plant survival, including aromatic amino acids (like phenylalanine, tyrosine, and tryptophan), hormones, and vitamins. Glyphosate interferes with an enzyme (EPSPS) at a key step in this process, preventing plants from making these important nutrients. As a result, weeds exposed to glyphosate wither and die, while genetically modified crops designed to resist glyphosate continue to grow.

Once applied, glyphosate starts to break down in plants and is further broken down in the soil. However, the speed at which it degrades varies depending on soil type (clay vs. sandy), pH levels, and the soil’s microbial community. Recent studies10 have shown that glyphosate can and is persisting in the environment, and it has been found in air, rainwater, drinking water, food, and even in human urine and breast milk10. This raises concerns about its impact on ecosystems, crop health, nutrition, and human health.

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Does glyphosate exposure cause dysbiosis?

Glyphosate was originally marketed as being safe for humans, on the basis that humans don’t have a shikimate pathway. However, the increased understanding of the importance of our microbiome to our overall health makes this sales pitch an obvious falsehood. Recent studies11,12 suggest that glyphosate residues in food may negatively impact human health by affecting the gut microbiome and a 2011 patent for glyphosate as an antibiotic provides further evidence for its damaging effects on the microbiome beyond the shikimate pathway effects.  

Let's look at how glyphosate exposure may potentially contribute to gut dysbiosis, an imbalance in the gut bacterial populations. 

Glyphosate inhibits EPSPS activity in microbes, but gut bacteria express two classes of EPSPS enzymes (I and II).

In the human gut microbiome, opportunistic pathogens are more resistant to glyphosate compared to most commensal (beneficial) bacteria, which are sensitive to the effects of glyphosate. Researchers hypothesize that chronic exposure to glyphosate via diet may help foster a pathogenic (dysbiotic) gut environment13. Research in cattle has shown that glyphosate selects for neurotoxin-producing Clostridium botulinum species13.

A dysbiotic gut environment will affect commensal bacteria like Lactobacilli and Bifidobacteria that contribute to several protective mechanisms essential for gut health like the synthesis of short-chain fatty acid synthesis like butyrate and conferring an anti-inflammatory gut environment14. Butyrate is the primary energy source for intestinal cells and a disturbance in butyrate synthesis will compromise gut wall health14. 

Additionally, commensal bacteria produce protein-degrading (including gluten and gliadin) enzymes like subtilisin and generate enzymes that mimic human protein-degrading enzymes like DPP-415. Dpp-4 is an enzyme that breaks down proteins (including dietary peptides, gut hormones like GLP-1, etc) into smaller fragments and a reduction in DPP-4 may contribute to impaired protein digestion.

Opportunistic pathogens like S. aureus and S. pneumonia build resistance to glyphosate and can contribute to a range of infections (including skin and respiratory tract infections), produce enzymes and toxins that may disrupt epithelial barriers, and contribute to inflammation, leading to tissue damage13.

Gluten, glyphosate residues, and the gut microbiome

Glyphosate is used on more than 60 crops including cereals, oilseeds, lentils, and legumes. Even when applied within the maximum permitted limits, it may result in unintended cumulative health effects.

High humidity increases glyphosate retention in crops. Although sellers warn farmers that applying glyphosate when seed humidity exceeds 30% can result16 in residues surpassing allowable limits, the ground reality showcases the breadth and depth of glyphosate infiltration in our ecosystems.

Gut bacteria that display gluten-degrading activity include B. licheniformis, B. subtilis, B. pumilus, B. longum, C. sordellii, C. perfringens, C. botulinum/sporogenes, C. butyricum/beijerinckii, E. faecalis, E. faecium, P. acnes, P. acidilactici, etc8. Chronic glyphosate exposure via diet may lead to a reduction in the abundance of protective commensal bacteria including gluten-degrading bacteria and an increase in proinflammatory bacteria13. 

An animal study17 showed that glyphosate reduces the activity of important digestive enzymes like trypsin, lipase, and amylase in the stomach which leads to the hypothesis that compromised protein degradation breakdown in the stomach. This reduction in enzyme activity may impair the breakdown of proteins, allowing larger, undigested protein fragments to pass into the small intestine and colon. This could lead to increased activity of harmful bacteria, potentially allowing undigested food particles and bacterial toxins (endotoxins) to pass through a weakened gut barrier, raising concerns about gut health.

If you're looking to support your gut health and bolster your immune system, consider incorporating Sugar Shift® and Ideal Immunity®, which feature beneficial strains like B. subtilis, B. longum, and P. acidilactici associated8 with gluten degrading capabilities. These powerful probiotics can help enhance your digestion and promote a balanced microbiome, ensuring you reap the full benefits of your diet while mitigating the potential impacts of dietary glyphosate exposure!

Glyphosate toxicity and human health

The increasing use of glyphosate in agriculture necessitates a better understanding of its impact on human and animal gut microbiomes. Our gut microbiome hosts trillions of microbes and glyphosate targets an essential mechanism that beneficial microorganisms need for their survival. 

Chronic glyphosate exposure may alter the gut microbiome by promoting dysbiosis, favoring pathogenic bacteria that are generally resistant to glyphosate over beneficial ones that facilitate gluten digestion. 

Previously, we’ve highlighted how lipopolysaccharides (LPS), an endotoxin from pathogenic Gram-negative bacteria, can leak through a compromised gut barrier, leading to inflammation. Similarly, undigested food peptides like gliadin can participate in weakening the barrier and triggering an autoimmune condition like celiac disease. 

Research indicates that previously considered safe residues of glyphosate can be physiologically relevant and may significantly affect our health. Glyphosate safety recommendations were made at a time when we were still at the onset of mapping the complex relationship we share with our gut residents. However, the rising tide of research linking glyphosate exposure with various health issues, including chronic kidney disease2,10, reproductive problems2,10, and irritable bowel syndrome2,10 begs the question if glyphosate should have any place in our food systems.

References

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