How does gluten cause leaky gut?

Leaky gut is the bridge between a dysfunctional digestive system and how it influences the rest of the body, accounting for the systemic, non-gastrointestinal manifestations of gluten intolerance and dysbiosis. So the story of your chronic inflammation, abdominal pains, sore, swollen joints, hormonal imbalances, skin issues, brain fog, mood disorders and the host of other signs and symptoms that come with having a dysfunctional gut starts with the leaky little junctions between your intestinal cells.

What is leaky gut?

Leaky gut is a term for increased intestinal permeability, where the spaces between intestinal cells open at the wrong times, and stay open for too long, losing the ability to keep intestinal contents like undigested food particles, bacteria and chemicals out of the tissues below the cells. There, these substances come into contact with immune cells, which raise the alarm and activate an inflammatory response that can cause intestinal damage, trigger inflammation throughout the body and possibly result in food intolerances and autoimmune diseases. 

The spaces between intestinal cells, called tight junctions, are held together by a complex scaffold of proteins rooted in each neighboring cell and connecting in the tight junctions. They open or loosen to allow small nutrients like water, calcium, chloride and magnesium to pass through, in what is called paracellular absorption. They’re triggered by substances in the intestinal lumen, or space inside the intestine, attaching to different receptors that stick out of the cells. This causes a chain reaction that leads to changes in the tight junction proteins (Kiela & Ghishan, 2016). 

Scientists think that another role for tight junctions may be to open wide and allow water to rush into the intestinal lumen, flushing out invading bacteria. Bacteria, their byproducts and gluten, which is sometimes broken into amino acid sequences that mimic the membranes of bacteria, can attach to receptors and trigger this process, resulting in the diarrhea often seen in dysbiosis and gluten intolerance (Fasano, 2011).

What foods cause leaky gut?

High sugar or high fat diets can cause dysbiosis, an imbalance of gut microbes, as certain microbes feast on the excess sugar and fat. They produce a substance called lipopolysaccharide (LPS) that can attach to cell receptors and downregulate or reduce production of tight junction proteins by the cell. High fat diets also increase secretion of bile acids, which the body produces to help absorb the fat, that also downregulate tight junction proteins (Rohr et al., 2020). Glucose, a simple sugar from refined carbohydrates and sweets, can bind to receptors and trigger opening of tight junction proteins (Suzuki, 2020). But the biggest culprit in leaky gut is gluten. 

Gluten causes dysbiosis as LPS-producing gut microbes are drawn to the small intestine to feed on incompletely-digested gluten peptides (Davila et al., 2013). It also binds to receptors on intestinal cells called CXCR3 receptors, which trigger tight junctions to open, and triggers the cells to release a substance called zonulin. Zonulin is a potent activator of tight junction disassembly, causing some of the proteins that hold the scaffold together to detach from each other and loosen the tight junction (Vanuytsel et al., 2013). 

Does everyone get leaky gut from gluten?

Some research shows that people who have a gene to produce a type of zonulin called pre-haptoglobin-2 have a more robust inflammatory response, more reactive immune system and higher risk of inflammatory bowel disease, though more research on its connection with gluten intolerance is still needed (Vanuytsel et al., 2013). One study found that up to 93% of celiac patients have at least one copy of the zonulin gene (Fasano, 2011).

When intestinal tissue samples from those with celiac patients and non-celiac controls are exposed to gluten, zonulin increases and tight junctions open in both, but those with celiac have a higher and longer-lasting release of zonulin and greater intestinal permeability than those who don’t have celiac (Lammers et al., 2008). Another study showed that celiac and gluten-sensitive subjects have the same level of increase in intestinal permeability when exposed to gluten.  Also, the non-celiac controls in that study had significantly higher levels of IL-10, a chemical that reduces intestinal permeability, indicating that those with celiac and gluten sensitivity suffer from a lack of adequate IL-10 (Hollon et al., 2015). 

Activating the zonulin pathway does’nt always lead to a leaky gut and resulting chronic inflammation. It also requires genetic components, dysbiosis and immune dysfunction, and other factors like stress and, or course, your diet can influence your susceptibility. 

If you think you’re suffering from leaky gut, Alimental’s Gut-Skin Axis Restoration Program is a step-by-step, evidence-based resource that will help you restore your gut health. Check it out here. 

References

Davila, A. M., Blachier, F., Gotteland, M., Andriamihaja, M., Benetti, P. H.,

Sanz, Y., & Tomé, D. (2013). Re-print of "Intestinal luminal nitrogen metabolism: Role of the gut microbiota and consequences for the host". Pharmacological research, 69(1), 114–126. https://doi.org/10.1016/j.phrs.2013.01.003

Hollon, J., Puppa, E. L., Greenwald, B., Goldberg, E., Guerrerio, A., & Fasano,

A. (2015). Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients, 7(3), 1565–1576. https://doi.org/10.3390/nu7031565

Kiela, P. R., & Ghishan, F. K. (2016). Physiology of intestinal absorption and

secretion. Best Practice & Research. Clinical Gastroenterology, 30(2), 145–159. https://doi.org/10.1016/j.bpg.2016.02.007

Rohr, M. W., Narasimhulu, C. A., Rudeski-Rohr, T. A., & Parthasarathy, S.

(2020). Negative effects of a high-fat diet on intestinal permeability: A review. Advances in Nutrition (Bethesda, Md.), 11(1), 77–91. https://doi.org/10.1093/advances/nmz061

Suzuki, T. (2020). Regulation of the intestinal barrier by nutrients: The role

of tight junctions. Animal Science Journal = Nihon Chikusan Gakkaiho, 91(1), e13357. https://doi.org/10.1111/asj.13357

Vanuytsel, T., Vermeire, S., & Cleynen, I. (2013). The role of haptoglobin

and its related protein, zonulin, in inflammatory bowel disease. Tissue barriers, 1(5), e27321. https://doi.org/10.4161/tisb.27321