Why Can’t They Finger Leaky Gut as Causing Gluten Intolerance?

I saw an article titled” Scientists Have Finally Identified Where Gluten Intolerance Begins” and thought, “Huh? Haven’t we known for a long time that it begins with a leaky gut?” I read the article expecting to read that Zonulin release from high Gliadin in modern hybridized wheat causes a leaky gut, letting proteins cross the gut before being digested and this causes the immune system to attack, giving people symptoms.

The article I read instead is summarized below. This is recent research on celiac disease, focusing on the role of intestinal epithelial cells in triggering the immune response to gluten. Here are the key points:

Research Findings

– Scientists from McMaster University identified a crucial role played by cells lining the gut in celiac disease[1][2].
– The intestinal epithelium actively participates in directing the inflammatory response to gluten, rather than being a passive bystander[1][2].

Celiac Disease Background

– Celiac disease affects about 1% of the population and has doubled in prevalence over the past 25 years[1].
– It is an autoimmune disorder triggered by gluten proteins found in wheat, barley, and rye[2].
– Currently, the only treatment is strict adherence to a gluten-free diet[1][2].

Genetic Factors

– 90% of celiac patients carry genes encoding the HLA-DQ2.5 protein, while most of the remaining 10% have HLA-DQ8[2].
– These proteins present gluten peptides to immune cells, triggering an autoimmune response[2].

Research Methods

– The team used transgenic mice and created intestinal organoids to study the immune response[1][2].
– They examined the expression of immune complexes in intestinal cells of celiac patients and mice with human celiac genes[2].

Implications

– This discovery could lead to new targeted therapies for celiac disease[1][2].
– Understanding the role of epithelial cells may help develop treatments that don’t require complete gluten avoidance[2].

The Missing Part of the Picture

These researchers zeroed in on part of the mechanism, but not where the disease begins, not the cause as I see it. The article does not mention Zonulin, a protein that regulates intestinal permeability and has been implicated in celiac disease pathogenesis. Sure, HLA-DQ2.5 protein presents gluten peptides to immune cells, but not if they aren’t crossing the gut barrier improperly before they are properly digested.

HLA-DQ2.5 is located on the membrane of antigen-presenting cells. These antigen-presenting cells include Macrophages in the lamina propria of the intestine, Dendritic cells and B cells. The intestinal lamina propria is composed of loose connective tissue and contains: Blood vessels, Lymphatic vessels (lacteals in the small intestine), Immune cells (lymphocytes, macrophages, plasma cells), Fibroblasts, Collagen and elastin fibers.

Zonulin: What it is, What it Does

Zonulin is a 47 kDa paracrine protein secreted by intestinal epithelial cells. It functions as a modulator of tight junctions between intestinal epithelial cells. Zonulin is considered a marker of impaired intestinal mucosal barrier function. Zonulin binds to specific receptors on intestinal epithelial cells. This binding activates the zonulin pathway, which leads to: Activation of epidermal growth factor receptor (EGFR), Triggering of protease-activated receptor 2 (PAR2), Separation of ZO-1 and occludin proteins from tight junction complexes.

When tight junctions are opened by zonulin, it increases intestinal permeability. This increased permeability allows antigens to pass from the intestinal lumen into the lamina propria. In the lamina propria, these antigens can interact with immune cells, potentially stimulating an immune response. In other words, without leaky gut, your system is not going to overreact.

Physiological and Pathological Roles

Under normal conditions, zonulin helps prevent bacterial colonization by promoting fluid secretion into the intestinal lumen. In pathological states, overproduction of zonulin can lead to prolonged opening of tight junctions. Excessive zonulin levels may contribute to autoimmune diseases by allowing increased antigen trafficking through the intestinal barrier.

Zonulin and Gluten

Gliadin, a component of gluten found in wheat, barley, and rye, has been identified as a powerful trigger for zonulin release in the intestine. This triggering effect occurs with traditional wheat varieties and is not specific to or caused by genetic modification, however, most modern wheat has been hybridized to increase gluten (including gliadin) content. While there have been experimental GM wheat varieties, most commercial wheat is not genetically modified. Changes in gliadin content are primarily due to traditional breeding and hybridization techniques.

Is Gliadin-Free Gluten Available?

Well, not in wheat. You can avoid it by eating other grains, but other proteins cause problems as well. Gliadin specifically refers to the protein found in wheat. The corresponding proteins in rye and barley are called secalin and hordein, respectively[11]. Gliadin is one of the main protein components of gluten, found primarily in wheat and related grains like barley and rye. It makes up approximately 30% of the total protein in wheat grain. There is no “gliadin-free gluten” available. Gluten-free products and diets are by nature gliadin-free, as gliadin is a component of gluten. For those extremely sensitive, a completely grain-free diet may be necessary to avoid all gluten-related proteins.

There are enzyme supplements like GliadinX that aim to break down gliadin and other gluten proteins, but these do not make foods “gliadin-free” – they are meant to help digest small amounts of accidental gluten exposure[12].

Will Papaya or Bromelain Break Down Gluten to Avoid Symptoms?

Bromelain (from pineapple) is a protease enzyme that can help break down proteins. While it may aid in general protein digestion, there’s no specific evidence that it’s effective against gluten.

Caricain, an enzyme found in papaya, has shown some ability to break down gluten proteins. A study comparing nine commercial supplements found GluteGuard (containing papaya enzyme) to be among the most effective at breaking down gluten epitopes.

Based on the search results and scientific evidence, papaya and bromelain enzymes may help break down gluten to some degree, but they are not a cure or replacement for a gluten-free diet for those with celiac disease or gluten sensitivity.

Having Any Kind of Inflammation? Stop Gluten for a Month and See if it Improves

Inflammatory response: The increased intestinal permeability allows partially digested gluten proteins to enter the bloodstream, triggering an inflammatory response that can further damage the intestinal lining.

Non-celiac gluten sensitivity: While not as well-defined as celiac disease, NCGS is increasingly recognized as a condition where gluten triggers symptoms without celiac-specific antibodies, often involving leaky gut.

Broader implications: This cycle can lead to systemic inflammation and autoimmune responses, extending beyond just digestive symptoms.

Why is the Link Between Gluten and Leaky Gut Not Better Known?

While it is difficult to say with certainty, here are some relevant considerations:

1. Agricultural interests: The wheat and grain industries are economically and politically powerful in many countries. There may be resistance to research or public health messaging that could negatively impact demand for wheat products.
2. Food industry influence: Many processed foods contain gluten. Companies producing these foods may lobby against stricter labeling or dietary recommendations.
3. Medical establishment inertia: The mainstream medical community can be slow to accept new paradigms, especially around diet and nutrition. There may be institutional resistance to shifting away from long-held views on gluten and celiac disease.
4. Research funding priorities: Government and private funding for nutrition research often favors certain topics over others. Studies on gluten sensitivity and leaky gut may not be prioritized.
5. Diagnostic criteria debates: There’s ongoing debate about how to define and diagnose non-celiac gluten sensitivity. This lack of consensus can impact research and treatment guidelines.
6. Pharmaceutical interests: If dietary changes alone could address many gluten-related health issues, it could reduce demand for certain medications.
7. Ideological factors: Some may view the focus on gluten sensitivity as part of broader “fad diet” trends, leading to skepticism of related research.

There is a big push still in 2024 to eat a “balanced diet” which includes whole grains. If it were admitted that some grains are making people sick in the first place, might that be a problem?

Gluten-free Whole Grain Options

• Millet: A gluten-free grain that is rich in magnesium and can be used in various dishes.
• Brown Rice: A nutritious alternative to white rice, rich in fiber and minerals.
• Quinoa: A complete protein containing all nine essential amino acids, making it an excellent choice for vegetarians and vegans.
• Oats: High in soluble fiber, oats can help lower cholesterol levels and improve heart health.

Remember that millet, quinoa, and brown rice are naturally gluten-free but may have cross-contamination risks. Oats are gluten-free but very often contaminated unless certified.

Read More
^{[1] https://www.sciencedaily.com/releases/2024/08/240809135706.htm
[2] https://www.sciencealert.com/scientists-have-finally-identified-where-gluten-intolerance-begins
[3] https://www.news-medical.net/news/20240809/Breakthrough-study-identifies-intestinal-epitheliums-role-in-celiac-disease-gluten-response.aspx
[4] https://www.mcmasterceliacclinic.ca/ongoing-research
[5] https://medicine.healthsci.mcmaster.ca/surprising-impacts-of-common-food-additive-on-gut-health/
[6] https://www.sciencedirect.com/topics/medicine-and-dentistry/zonulin
[7] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/zonulin
[8] https://www.mdpi.com/1422-0067/24/8/7548
[9] https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.871713/full
[10] https://journals.physiology.org/doi/full/10.1152/physrev.00003.2008
[11] https://www.sciencedirect.com/topics/neuroscience/gliadin
[12] https://www.amazon.com/GliadinX-90-Capsules-Scientifically-Proven/dp/B07B9S7PD2}