Healing Tight Junctions of the Intestines - 4 Proven Methods to Heal your gut

Reading Time - 8 Minutes

Everything that makes up your body comes from food and water consumed and then processed by your digestive system. A key component to a healthy gut are epithelial tight junctions. Basically, the cells that make up the outside surface of your intestines are responsible for the absorption of water and beneficial nutrients and also block the absorption of toxins and inflammatory molecules. These Epithelial tight junctions maintain the intestinal barrier while regulating permeability of ions, nutrients, and water. The tight junctions are effectively where the cells of the intestine press up against each other, leaving no spaces for things to pass into the bloodstream without first going through the cells themselves.

When the epithelial tight junctions of the gut are weakened, the increased intestinal permeability can act as a trigger for the development of intestinal and systemic diseases such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and Crohn’s Disease (1). A more general term for these conditions is leaky gut.

The science behind healing these tight junctions is still incomplete, but there are a few methods that have been investigated and found to be successful. Read how zinc, phytonutrients, bacteria, and even dirt can help you heal your digestive system.

Supplement with Zinc

Zinc deficiency is known to result in epithelial barrier leak in the GI tract (2,3), though the exact methods of which are still unknown. In order to learn about about this symptom of zinc deficiency, researchers took colon epithelium (Caco-2) cells and measured the electrical resistance of the tight junctions before and after 7 days of zinc supplementation (4).

The zinc increased the electrical resistivity of the epithelial tight junctions by 61%, a good sign of a strong healthy gut. It was found that the the zinc-induced barrier tightening held true for small electrolyte ions but not for small non-electrolytes. More research is needed here, but increased permeability for non-electrolytes after zinc supplementation is not necessarily a bad thing. For example, during active transport of glucose from the gut to the bloodstream (such as after a meal), increased permeability is observed in intestinal epithelial cells. It has also been observed that zinc supplementation strengthens the lung epithelial cell barrier (5).

Zinc supplementation tightens intestinal cell junctions yet also aids absorption of beneficial nutrients. To supplement with Zinc, it’s best to take it with copper at a 15:1 ratio, so as to avoid a copper deficiency (6).

 
Oysters

I personally supplement with Jarrow Formula’s Zinc Balance supplement everyday which contains 15 mg of zinc and 1 mg copper, taken with a meal to avoid nausea. If you’re look for a natural food source, oysters are the way to go! Six medium oysters provide 32 mg of zinc. The recommended RDA for men is 11mg (which is too low to begin with).

 

Consume Flavenoids

 
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More research is coming out all the time regarding maintaining proper gut health, and recently it was observed that flavenoids such as genistein (soy phytoestrogen) quercetin (plant pigment), and epigallocatechin gallate (EGCG, green tea polyphenol) exert protective effects on the intestinal tight junction barrier (7).

 

Genistein was found in multiple studies to have a protective effect on the gut. Genistein ameliorate (improved upon) oxidative stress (8) that colon epithelium (Caco-2) cells were subjected too. Studies have also observed that genistein ameliorates the impairment of intestinal tight junction barrier function by inflammatory cytokines (9) and enteric bacteria (10).

Quercetin was recently investigated for it effects on intestinal tight junction health. When rats were fed a quercetin rich (1%) diet, intestinal tight junction function was enhanced through the increased assembly of important tight junction proteins (11). Quercetin is found in many fruits, vegetables, leaves, and grains, with red onions and kale containing appreciable amounts.

EGCG is a polyphenol found in green tea well known for its positive anti-inflammatory and anti-oxidant effects. When human intestinal T84 cells were exposed to a stressor, tight junction function was reduced but subsequent administration of EGCG completely reversed the changes (12). Related to the next section below, supplementation of EGCG to rats improved nutrient absorption from fats and proteins, which simultaneously reducing adipose tissue (13). It was found that in rats dietary EGCG positively affects the growth of certain species of gut microbiota partly responsible for regulating energy metabolism in the body through the production of short chain fatty acids in the colon.

Flavenoids and other plant polyphenols can have powerful beneficial effects on the gut, and the best way to make sure you consume adequate amounts of these compounds is to eat a diet rich in organic vibrantly colored fruits and vegetables.

Take Care of your Gut Bacteria

 
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The human body contains approximately the same amount of bacteria within the body as human cells, and the interactions between our gut bacteria and digestive system can have profound impacts on ones health. A healthy gut contains an entire ecosystem of commensal (helpful) bacteria which work in unison with each other and the human gut to produce a safe stable environment for the absorption of nutrients.

 

It’s been shown that intestinal bacteria can help beneficially regulate tight junction permeability (14). For example, the molecule indole, secreted by commensal Escherichia coli increases epithelial tight-junction resistance, attenuating indicators of inflammation in the process (15). Indole also prohibits pathogenic E. coli movement, motility, and attachment to epithelial cells. Attachment of pathogenic bacteria to epithelial tight junctions is one of the main stressors the gut can experience (16,17), and one of the best ways to fight pathogens is to maintain a strong healthy gut full of commensal bacteria.

A healthy diet that prioritizes unprocessed foods is a great way to build a healthy gut microbiome (18), and supplementing with probiotics has also been shown to be helpful in improving the microbiome (19). I alternate between taking two probiotic supplements almost daily. 80% of the time I supplement with Organifi’s Biotic Balance which is 50 million CFU’s (colony forming units) comprised of 10 different Bifidio and Lacto bacterial strains. 20% of the time I use Nature’s Bounty Probiotic 10, which contains 20 million CFU’s comprised of 10 different bacterial strains. I like to alternate so I’m always exposing myself to new strains

Eat Dirt

Actually, eat prehistoric dirt. Interesting research has been performed on the effect a supplemental lignite extract had on the tight junctions of epithelial cells. Lignite is a soft, brown, combustible, sedimentary rock formed from naturally compressed peat which contains traces of plant structure and materials. It is believed these ancient plant materials have protective effects on the gut.

 
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In one study (20), researchers cultured small bowel (IEC-6) and colon epithelium (Caco-2) cells, and then the lignite extract was administered to one group of each while the others were left as the controls for 12 hours. After 12 hours had elapsed, glyphosate, a herbicide more commonly known as Roundup and also a known gut disruptor (21), was applied to all groups.

 

The control groups showed a large degradation in cellular tight junctions from the application of glyphosate, while the lignite extract group nullified the effects of the glyphosate. Basically supplementing with a lignite extract was shown to increase epithelial tight junction strength, and when exposed to glyphosate, a known gut disruptor ubiquitous within the food supply, it nullified the harmful effects of the glyphosate.

 

In another study (22) with the same survey design, small bowel (IEC-6) and colon epithelium (Caco-2) cells were cultured. Half were left as a control and the other half were administered the same supplemental lignite extract. After 12 hours, researchers this time used gliadin, one of the main components of wheat gluten, to damage the tight junctions of the cells. Same as the glyposate, the application of gliadin peptides severely damaged the tight junctions of the small bowel and colon cells, while the lignite extract nullified the effects.

 

After reading this lignite research, I bought a bottle of the same supplement used in the research, Restore, and supplemented with it fairly consistently for 2 months. I noticed that when I supplemented with Restore before and after I occasionally ate a processed wheat based (gluten and glyphosate rich) item (such as a pastry), my gut which would normally flare up would instead be fine. I didn’t push my consumption of wheat too much as wheat based foods are generally unhealthy in the first place, but for the occasionally life event such as a family gathering or birthday, using Restore sure made maintaining my gut health much easier.


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Stefan Burns

Stefan Burns is the creator and main author of Wild Free Organic. A swimmer in high school, soon afterwards he discovered a passion for the health, wellness, and fitness fields. Stefan is a jack of all trades, expertly knowing how to use all the different wellness “tools” available to radically and permanently transform one’s health, from fasting and sauna usage to calisthenics and powerlifting.

To learn more about Stefan Burns visit his website or follow him on Instagram @stefanburnswellness.


 

References

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  2. Bao S, Knoell DL. Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1132-41.

  3. Finamore A, Massimi M, Conti devirgiliis L, Mengheri E. Zinc deficiency induces membrane barrier damage and increases neutrophil transmigration in Caco-2 cells. J Nutr. 2008;138(9):1664-70.

  4. Wang X, Valenzano MC, Mercado JM, Zurbach EP, Mullin JM. Zinc supplementation modifies tight junctions and alters barrier function of CACO-2 human intestinal epithelial layers. Dig Dis Sci. 2013;58(1):77-87.

  5. Bao S, Knoell DL. Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol Lung Cell Mol Physiol. 2006;291(6):L1132-41.

  6. Hoffman HN, Phyliky RL, Fleming CR. Zinc-induced copper deficiency. Gastroenterology. 1988;94(2):508-12.

  7. Suzuki T, Hara H. Role of flavonoids in intestinal tight junction regulation. J Nutr Biochem. 2011;22(5):401-8.

  8. Rao RK, Basuroy S, Rao VU, Karnaky KJ, Gupta A. Tyrosine phosphorylation and dissociation of occludin-ZO-1 and E-cadherin-beta-catenin complexes from the cytoskeleton by oxidative stress. Biochem J. 2002;368(Pt 2):471-81.

  9. Wells CL, Jechorek RP, Kinneberg KM, Debol SM, Erlandsen SL. The isoflavone genistein inhibits internalization of enteric bacteria by cultured Caco-2 and HT-29 enterocytes. J Nutr. 1999;129(3):634-40.

  10. Schmitz H, Fromm M, Bentzel CJ, et al. Tumor necrosis factor-alpha (TNFalpha) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J Cell Sci. 1999;112 ( Pt 1):137-46.

  11. Suzuki T, Hara H. Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr. 2009;139(5):965-74.

  12. Watson JL, Ansari S, Cameron H, Wang A, Akhtar M, Mckay DM. Green tea polyphenol (-)-epigallocatechin gallate blocks epithelial barrier dysfunction provoked by IFN-gamma but not by IL-4. Am J Physiol Gastrointest Liver Physiol. 2004;287(5):G954-61.

  13. Unno T, Sakuma M, Mitsuhashi S. Effect of dietary supplementation of (-)-epigallocatechin gallate on gut microbiota and biomarkers of colonic fermentation in rats. J Nutr Sci Vitaminol. 2014;60(3):213-9.

  14. Ulluwishewa D, Anderson RC, Mcnabb WC, Moughan PJ, Wells JM, Roy NC. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr. 2011;141(5):769-76.

  15. Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci USA. 2010;107(1):228-33.

  16. Guttman JA, Samji FN, Li Y, Vogl AW, Finlay BB. Evidence that tight junctions are disrupted due to intimate bacterial contact and not inflammation during attaching and effacing pathogen infection in vivo. Infect Immun. 2006;74(11):6075-84.

  17. Eichner M, Protze J, Piontek A, Krause G, Piontek J. Targeting and alteration of tight junctions by bacteria and their virulence factors such as Clostridium perfringens enterotoxin. Pflugers Arch. 2017;469(1):77-90.

  18. De filippo C, Cavalieri D, Di paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010;107(33):14691-6.

  19. Hemarajata P, Versalovic J. Effects of probiotics on gut microbiota: mechanisms of intestinal immunomodulation and neuromodulation. Therap Adv Gastroenterol. 2013;6(1):39-51.

  20. Gildea JJ, Roberts DA, Bush Z. Protective Effects of Lignite Extract Supplement on Intestinal Barrier Function in Glyphosate-Mediated Tight Junction Injury. J Clin Nutr Diet. 2017, 3:1.

  21. Samsel A, Seneff S. Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Interdiscip Toxicol. 2013;6(4):159-84.

  22. Gildea JJ, Roberts DA, Bush Z (2016) Protection against Gluten-mediated Tight Junction Injury with a Novel Lignite Extract Supplement. J Nutr Food Sci 6: 547.