Leaky Gut, Lectins, and Autoimmune Disease: Is There a Connection?

What are lectins?

Lectins are a diverse family of carbohydrate-binding proteins that are highly specific for the sugar molecules to which they attach. This binding affinity of lectins may result in agglutination or clumping of various cell types. These sugar-binding proteins are not digestible by humans and therefore may cause health problems. Perhaps the best-known lectin-like molecules are gliadins found in gluten.

Where are lectins found?

Lectins are widely distributed in nature, but the highest concentrations can be found in foods such as red kidney beans, soybeans, peanuts, potatoes, wheat, and tomatoes.

What is the evidence that lectins can do harm?

Animal studies have shown that consumption of lectins can induce physiological changes that are responsible for various health problems. Lectins can bind to a diverse family of 9-carbon sugars called sialic acids, which reside on the surface of the epithelial cells that line the intestines. Once bound, these sugar-binding proteins may cause inflammation, damage to the intestinal lining, and “leaky gut”. In a particular study, researchers showed that, in vitro, the lectin wheat germ agglutinin (WGA) severely diminishes the integrity of the intestinal epithelial layer while promoting the secretion by immune cells of pro-inflammatory cytokines (de Punder, 2013). These findings suggest that WGA affects the integrity of the intestinal epithelial layer by directly binding and inducing immune cells to secrete inflammatory cytokines, resulting in increased intestinal permeability, a hallmark of the leaky gut syndrome. The hypothesis is that abnormal intestinal permeability allows lectins and endotoxins to enter systemic circulation where they can trigger or promote autoimmune disease.

Autoimmune diseases can develop due to lectins because they are able to bind to specific carbohydrates on the surface of different body tissues. Lectins that are bound to certain tissues will initiate immune responses against both lectins and the specific tissues that the lectins have attached to. Islet cells of the pancreas have a specific type of sialic acid, called N-acetyl lactosamine, to which tomato lectin (and possibly lectins of wheat, potato, and peanut) can bind (Vojdani et al, 2020). This would result in pancreatic islets presenting foreign antigens that are susceptible to attack from the immune system, potentially leading to type 1 diabetes mellitus. Several studies have shown that rats with a diet consisting of soybeans and wheat had the highest incidence of insulin-dependent diabetes (Scott et al, 1996). The data from these studies suggest that lectins may promote autoimmune attack that leads to the destruction of the pancreatic islets, contributing to type 1 diabetes mellitus.

Lectins can also stimulate autoimmune attack via molecular mimicry. The presence of lectins in systemic circulation will stimulate the immune system to produce specific antibodies that target and destroy the undigested lectins. However, the same antibodies can cross-react with other cell types that share the same molecular structure as lectins, which results in autoimmune disease. In one study, serum containing antibodies against lectins of wheat showed cross-reactivity with 34 out of 62 tested tissue antigens, including thyroid, pancreas, liver, heart, and other organs (Freed et al, 1999). Therefore, this finding indicates that the same antibody that targets lectin, could also be aiming for tissues of various organs such as the thyroid, causing Hashimoto’s thyroiditis.

What is the best model system for research on the biological effects of dietary lectins?

Mouse are the best model system so far when conducting research on the potential harmful effects of lectins on humans. This is because mice have similar anatomy, physiology, and genetic traits as humans. Thus, studying the effects of lectins on mice will allow better understanding of what those effects are tn humans. Furthermore, the genome of mice can be easily manipulated therefore conditions can be altered to fully see the harmful effect of lectins.

Should humans be concerned about lectins? if so, can lectins be “cooked out”, bound up or otherwise neutralized in human nutrition?

Although numerous studies have indicated the harmful effects of consuming lectins found in fruits and vegetables, not everyone consuming lectins will have the same health problems, if any. This is because there are variations of glycoconjugates (cell surface sugars that are linked with specific lipids or proteins) among individuals (Uchigata et al, 1987). Thus, some individual glycoconjugate configurations prevent lectins from binding to the surface of cells.

Specific lectins like those found in wheat can be inactivated by the sugar N-acetyl glucosamine and its polymers (Freed 1999). Since lectins are specific to the sugars they bind, supplements containing the sugar N- acetyl glucosamine potentially could inactivate lectins like those found in wheat, preventing them from binding to human tissues.

Due to the globular structure of lectins, these proteins can resist elevated temperatures and digestive enzymes. However, some studies suggest that lectins found in wheat can be inactivated by the application of heat during the cooking process. Specifically, analysis of heat-stressed WGA using ELISA and western blot detection assays shows that increasing temperatures lead to a decline in the activity of WGA (Van et al, 2014).

Thus, consumption of lectins in some otherwise nutritious fruits and vegetables may be safe if lectins are inactivated.

REFERENCES

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Freed DL. Do dietary lectins cause disease? BMJ. 1999 Apr 17;318(7190):1023-4. doi: 10.1136/bmj.318.7190.1023. PMID: 10205084; PMCID: PMC1115436.

Panacer K, Whorwell PJ. Dietary Lectin exclusion: The next big food trend? World J Gastroenterol. 2019 Jun 28;25(24):2973-2976. doi: 10.3748/wjg.v25.i24.2973. PMID: 31293334; PMCID: PMC6603809.

Scott FW, Kolb H. Cows’ milk and insulin-dependent diabetes mellitus. Lancet. 1996 Aug 31;348(9027):613. doi: 10.1016/S0140-6736(05)64826-X. PMID: 8774587.

Uchigata Y, Spitalnik SL, Tachiwaki O, Salata KF, Notkins AL. Pancreatic islet cell surface glycoproteins containing Gal beta 1-4GlcNAc-R identified by a cytotoxic monoclonal autoantibody. J Exp Med. 1987 Jan 1;165(1):124-39. doi: 10.1084/jem.165.1.124. PMID: 2432147; PMCID: PMC2188266.

van Buul, V.J., Brouns, F.J.P.H., Health effects of wheat lectins: A review, Journal of Cereal Science. 2014 Mar; 59(2):112-117.

Vojdani A, Afar D, Vojdani E. Reaction of Lectin-Specific Antibody with Human Tissue: Possible Contributions to Autoimmunity. J Immunol Res. 2020 Feb 11;2020:1438957. doi: 10.1155/2020/1438957. PMID: 32104714; PMCID: PMC7036108.