Heal Tight Junctions of the Gut

Article by Stefan Burns - Updated July 2022. Join the Wild Free Organic email newsletter!

Food and water are the two building blocks for the human body from which everything is made of. The digestive system is what takes food and water and turns the nutrients pulled from them into all the various cells, proteins, enzymes, and compounds that keep life going. In the process of digestion, the body decides what nutrients it wants and which it doesn’t, and it uses a variety of mechanisms to make those discriminations.

The cells that make up the outside surface of the intestines have in-between them what are known are tight junctions. 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.

 
Cross-section view of intestinal epithelial cells. In this depiction, tight junctions are tight and the cells are healthily pressed up against one another.

Cross-section view of intestinal epithelial cells. In this depiction, tight junctions are tight and the cells are healthily pressed up against one another.

 

When the epithelial tight junctions of the gut are weakened and cells spread out, intestinal permeability is increased. Microbes and partially digested compounds that pass through these no-longer tight junctions can act as triggers 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.

There are a few methods that have been investigated and found to be successful in healing tight junctions. Read how zinc, phytonutrients, bacteria, and dirt can help you heal your digestive system.


Ready to Heal Your Gut?
 
Holistic Gut Health Guide
Sale Price:$12.95 Original Price:$18.95

Together the digestive system and microbiome are the foundation of health from which everything else is dependent on.

The Holistic Gut Health Guide contains all the information you need to identify and understand the gastrointestinal and microbiome problems you may have while also providing you the most effective natural methods you can use to heal your gut. No gut health problems are unsolvable, give yourself every possible advantage along your gut health journey by reading an implementing the advice shared in the Holistic Gut Health Guide.

Purchase
 

Some of the information in the Holistic Gut Health Guide isn’t common knowledge but when implemented it is highly effective in healing the gut and shifting the microbiome towards symbiosis. Give yourself every possible advantage along your gut health journey by reading an implementing the advice shared in the Holistic Gut Health Guide.


Heal Tight Junctions 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). There is a deep interaction between the digestive system, zinc, and the immune system.

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).

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 and are packed with other micronutrients. The recommended RDA for men is 11 mg and 8 mg for women, but daily supplementation of zinc between 10 - 40 mg is safe.

 

Consume Flavonoids to Heal Tight Junctions

Flavonoids such as apigenin, genistein (soy phytoestrogen), quercetin (plant pigment), and epigallocatechin gallate (EGCG, green tea polyphenol) exert protective effects on the intestinal tight junction barrier (7). Besides these specific phytochemicals, eating a diet rich in organic fruits and vegetables is the cornerstone of a healthy diet and with consistency will transform gut health.

 
Vibrant Vegetables - C.jpg
 

Genistein

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). If you want to consume genistein for these protective gut effects, fermented soy products like natto and tempeh are the healthiest and most bioavailable.

Quercetin

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. Quercetin is also found in green tea.

Green Tea Catechins (EGCG)

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. Store bought green tea is heavily oxidized and contaminated with herbicides, and therefore is not a good source of green tea catechins.

Pique Tea sells cold brew extracted and crystallized tea crystals which have up to 12x the antioxidants of normal green tea, and they are triple screened for hazardous compounds. For the most gut-healing polyphenols, I recommend their Sun Goddess Matcha or their Matcha Green Fasting Tea. A hot cup after a meal helps soothe the digestive system, and 2-3 cups a day during a green tea fast can heal the tight junctions of the gut very quickly. Use the coupon code WILDFREEORGANIC for 5% off at checkout.

Flavenoids and other plant polyphenols such as anthocyanins (found abundantly in elderberries) can have powerful beneficial effects on the gut. 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 the Microbiome

The human body contains 10x as many microbes within the body as human cells, and the interactions between our gut microbiome and digestive system can have profound impacts on 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.

 
Bacteria - C.jpg
 

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 symbiotic bacteria.

A healthy diet that prioritizes organic 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 don’t use probiotics often as I prefer fermented foods, though I have taken probiotics extensively and have a couple recommendations. Thorne makes a great leaky gut supplement, Perma-Clear, which contains key probiotic strains while also adding gut boosters like ginger and L-Glutamine. Mixing probiotics with herbs or supplements like SCRAM for parasites is a great way to favorably shift the microbiome.

 

Heal Tight Junctions with 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.

 
Restore Glyphosate Graph - C.png

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 glyphosate, 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. This was back when I are much more gluten, and I noticed that supplementing with Restore helped my gut issues tremendously. Restore helps by binding to gluten, and also dangerous pesticides. You can get this same effect if you eat any food that contains microparticles of clay and silt such as salad greens, squash, beans, and lentils.

Knowing this, Restore can be kept on hand as a protective supplement for the occasionally dietary one-off. Restore your gut health.

 

Heal Tight Junctions, Heal the Digestive System

There is a lot of misinformation out there when it comes to healing digestive maladies. and it is very difficult to know who to trust, what to do, and how long healing your gut will take.

I have a predisposition for gut health problems. My mother had Crohns and my aunt’s side of the family has celiac disease. I’ve struggled with leaky gut, IBS, SIBO, food allergies, gluten intolerance, and fructose intolerance for years. It was a very long process guided by research, experimentation, and mindfulness before I began to see rapid health improvements and my digestive system healed. This whole process was set back by the lack of scientific data on the microbiome, a critical component of the digestive system. It had to be learned intuitively.

One of the biggest breakthroughs I made was when I discovered glyphosate and the terrible effects it has on your microbiome and epithelial tight junctions. Once I made a serious effort to reduce my glyphosate exposure, by not eating foods laden with glyphosate (wheat and non-organic GMO produce) my gut health improved remarkably, and afterwards switching to a flexitarian diet healed my gut completely. When the gut is healthy, the rest of the body is healthy, and I have seen numerous other health improvements from healing my gut, starting with my hormonal system.

Take it from me, one of the most important things you can do to heal your gut is to heal your epithelial tight junctions. The easiest way to accomplish that goal into your routine is with a regular cup of green tea. Each cup of polyphenols will scavenge for undesirables and help your body to process the toxins out. Matcha Green Tea is one of the most effective gut healers known, just mind the caffeine.


Heal Your Gut Naturally
 
Holistic Gut Health Guide
Sale Price:$12.95 Original Price:$18.95
Purchase

If you read all the way here then it’s clear to me that you’re ready to do what it takes to finally restore your digestive system and gut microbiome back to healthy and optimal function.

I wrote the Holistic Gut Health Guide to help you accomplish exactly this! It contains all the information that you need to understand the gastrointestinal system, gut-brain axis, and microbiome in-depth, and the Holistic Gut Health Guide also educates you on the natural methods you can holistically use together like fasting and herbalism to transform your health from the inside out.

I’m so excited to be able to help you along your gut health and overall wellness journey with the Holistic Gut Health Guide! Please contact me with any questions you have and wishing you the best.

 

Medical Disclaimer: All information, content, and material of this website is for informational purposes only and is not intended to serve as a substitute for the consultation, diagnosis, and/or medical treatment of a qualified physician or healthcare provider.

Disclosure: Wild Free Organic is a member of various affiliate programs and if a purchase is made through one of our affiliate links a small commission is received. This does not affect your purchase price. Visit our disclosure page for more information.

References

  1. Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res. 2015;13(1):11-8.

  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.