Leaky Gut Syndrome

There’s intriguing evidence that autoimmune disorders may be related, at least in part, to a digestive system damaged by medications and unhealthy foods. This damage can also cascade into highly individualized symptoms that stump many physicians and may be a contributing factor to a great many diseases. The underlying cause may be what some physicians and researchers call “leaky gut syndrome,” also known as increased intestinal permeability.

To explain, your digestive tract is home to the vast majority of your body’s immune cells. After all, most “foreign” and potentially threatening microorganisms enter the body through the mouth. Our resident gut bacteria support the immune system by countering any disease-causing germs that piggyback on the food we eat.

Ideally, the gut wall functions as a gateway that allows only digested food molecules and nutrients to pass through and into the bloodstream. But this intestinal barrier can be compromised in a variety of ways. Antibiotics are among the worst offenders because they indiscriminately destroy many of the beneficial bacteria that inhabit our digestive tract.¹ Alcohol, caffeine, stress, the standard American diet, consuming foods you are allergic or sensitive to, certain medications (i.e. recurrent use of NSAIDs), and recreational drugs can also damage the gut lining. Even many types of processed foods can damage the gut lining.²

In fact, an article in the February 26, 2015 issue of the journal Nature reported that two emulsifying agents (cellulose gum and polysorbate-80), which are commonly used in processed foods, disrupted the normally protective interactions between intestinal bacteria and the gut wall. The result set the stage for inflammatory bowel disease and potentially obesity and metabolic syndrome.³ And as it turns out, gluten is especially well documented for its role in causing leaky gut syndrome.

The Broad Implications of Leaky Gut

While autoimmunity is certainly one concern associated with Leaky Gut Syndrome, there are numerous other problems associated with a leaky gut barrier. When the gut is inflamed and its barrier integrity compromised, it does not absorb nutrients properly, resulting in nutrient deficiencies. Detoxification pathways that line the gut are compromised, leading to increased absorption of toxins and increased burden on the liver. A damaged gut lining can adversely affect production of secretory IgA which the body uses to ward off infections, making one more susceptible to bacterial, yeast, virus, and protozoa invasion.

Leaky gut has been associated with

• neuroinflammatory diseases like Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (ALS);³³
• dermatological disorders such as eczema, psoriasis, and hives; ³⁴
• increased food and environmental sensitivities; ³⁵
• type I and II diabetes and insulin resistance,³⁶
• and a wide range of autoimmune diseases.

In some cases, it is not known whether the leaky gut is a cause of the disorder/disease or a symptom of it, but the implication is that intestinal barrier integrity is of the utmost importance.

The Gut Wall

The wall of the gastrointestinal (GI) tract is lined with highly specialized protein complexes called “tight junctions” (TJs), which serve as a gateway that either enables or blocks the passage of nutrients into the bloodstream. TJs also influence the body’s immune tolerance and response to bacteria, viruses, and foods. For example, a substance called zonulin regulates the permeability of TJs, and some people over-produce zonulin when they consume the protein gliadin, the main culprit in gluten. The over-production of zonulin ends up punching holes in the normally tight barrier created by TJs. ^{4 5 6 7 8 9}

As a consequence, gut-wall permeability increases, allowing large, incompletely digested food molecules to enter the bloodstream. Those incompletely digested food molecules trigger an abnormal immune response, an increase in inflammation, and sometimes a rise in immunoglobulin G (IgG).^{10 11} Not surprisingly, IgG levels are often elevated in patients with celiac disease and non-celiac gluten sensitivity.¹²

In fact, autoimmune diseases related to leaky gut syndrome may be only part of the problem. For example, the line between immune and autoimmune disorders gets blurred in inflammatory bowel diseases (e.g., Crohn’s disease), allergies, and asthma. All may be related to leaky gut syndrome, because the body’s immune system is misreading cues and reacting abnormally. Compelling research has also linked depression and autistic symptoms to gluten consumption and gut health—and possibly to leaky gut syndrome.^{13 14}

Dietary and Supplement Recommendations

Healing the gut requires dietary improvements and the use of certain supplements. The “5R” approach (Remove, Replace, Restore, Reinforce, and Rebalance) is a good place to start for comprehensive gut healing. (For more information please see Good Health Starts in the Gut). It starts by adopting a diet that eliminates gluten (found in wheat, rye, and barley) and any foods you may be sensitive or allergic to, as well as alcohol, coffee, and processed foods. Loren Cordain, Ph.D., a professor at Colorado State University, Fort Collins, and the leading expert on the Paleo diet, developed the Paleo Autoimmune Protocol (AIP) which many who suffer from autoimmune disorders have found helpful. It is a stricter version of the Paleo diet that eliminates foods that can irritate and damage the intestine. (For more information, google the AIP term.) The diet emphasizes quality proteins, such as fish, chicken, and grass-fed beef, along with ample amounts of high-fiber vegetables. The following supplements can help modulate the immune response and also fine tune healing of the gut wall.

Vitamin D

This vitamin, which is actually a hormone precursor, is an important regulator of immune system activities. Instead of just enhancing the immune system’s response to disease-causing microorganisms, vitamin D actually helps the immune system function “smarter.” In a recent study, Kassandra L. Munger, Sc.D., of Harvard University, and an international team of researchers found that vitamin D influenced the activity of a large number of genes involved in multiple sclerosis (MS), an autoimmune disease that affects 400,000 Americans. Munger’s finding is significant because growing evidence indicates that low vitamin D appears to be related to the risk of developing MS, as well as to its long-term progression.¹⁵ 

Try: 5,000 IU daily.

Probiotics

Prebiotics and probiotics improve the gut’s environment by promoting a healthy balance of bacteria which helps maintain a normal intestinal barrier. Prebiotics act as “food” for the good bacteria in the gut and are found in many fiber-rich foods (think fresh vegetables); common supplemental sources include FOS (fructooligosaccharide), inulin, psyllium, and ground flax seeds. Lactobacillus and Bifidobacteria species are the most popular types of probiotic supplements, and they appear to be “keystone species” that help maintain a supportive environment for other types of healthy gut bacteria. They also appear to have remarkable anti-inflammatory effects.¹⁶ L. rhamnosus may be of particular help in healing the gut barrier, and a particular type of probiotic yeast, Saccharomyces boulardi, also has been found useful in reducing gut inflammation and acute diarrhea.^{18 19} A French study found that a multi-species probiotic significantly reduced symptoms of IBS in women.

Try: A probiotic formula containing at least several species of Lactobacillus and Bifidobacteria to support general gut health.²⁰ For documented gut inflammation (e.g., inflammatory bowel disease), S. boulardi supplements may be of particular benefit.

Digestive enzymes

Our digestive tract and liver secrete a variety of digestive enzymes to break down different types of food molecules, such as proteins, fats, and carbohydrates. Some specific digestive enzyme formulas have anti-inflammatory benefits, possibly because of how they promote gut healing. Highly specialized enzymes, such as dipeptidyl peptidase IV (DPP-IV), enhance the breakdown of gluten. Although they won’t protect against the gluten in a slice of pizza, these enzymes might offer protection against occasional exposure to trace amounts of gluten.

Try: For general use, consider a product with several digestive enzymes. Products vary greatly, so follow label directions.

Colostrum

Found in the fluid before breast milk comes in, colostrum contains a variety of immune factors and is involved in normal cell growth and repair, all of which benefits newborns. Lactoferrin, which helps fight bacterial and viral infections, is one of the constituents of colostrum. A study of athletes found that colostrum reduced post-exercise gut permeability by more than 80 percent.²¹ Supplements are derived from cow’s milk.

Try: 500 mg daily.

L-glutamine

This amino acid was first used to heal stomach ulcers back in 1957.²² It’s now widely used by nutritionally oriented physicians to heal gut injury, including leaky gut syndrome. L-glutamine is the most abundant amino acid in the body, and its extra nitrogen atom helps the body assemble other amino acids. The benefits of L-glutamine may be enhanced when combined with bovine colostrum.²³

Try: Up to 400 mg four times daily.

N-acetyl glucosamine (NAG)

This little-known natural substance (not to be confused with glucosamine sulfate) also appears helpful in resolving leaky gut syndrome. In one study, researchers described its benefits in treating a condition similar to multiple sclerosis.²⁴ A second study of 12 children with either Crohn’s disease or ulcerative colitis received 3 to 6 grams of N-acetyl glucosamine daily. Eight of the children improved significantly.²⁵

Try: 3 to 6 grams daily, depending on the severity of symptoms.

Soluble fiber

This type of dietary fiber supports the growth of beneficial gut bacteria by acting as a food source. The beneficial gut bacteria in turn produce short-chain fatty acids (SCFA) like butyrate, which is the primary fuel source for colon cells. Together, soluble fiber and gut bacteria can have a potent anti-inflammatory effect and directly support the health of the colon cells. Low-fiber, high-sugar diets deplete anti-inflammatory gut bacteria.^{26 27 28}

Try: A soluble fiber supplement, following label directions for use.

Herbal remedies

Several herbal extracts have a long history of use in easing gut problems, and they may be of use in healing leaky gut syndrome. Licorice root is a folk remedy for heartburn, and it may provide benefits throughout the digestive tract. The most common supplemental form is called deglycyrrhizinated (DGL) licorice root. DGL licorice has had its glycyrrhizin removed because, in some people, it can increase blood pressure. Another herb, slippery elm, is derived from the inner bark of Ulmus rubra. The extract contains mucilage, which is believed to coat part of the digestive tract. Finally, herbal bitters, taken by the teaspoon, typically contain gentian but they may contain as many as 40 different plants. As the name suggests, bitters are anything but sweet, but do promote better digestion.

Try: Any of these herbs, but follow label directions.

Omega-3s

Few natural substances have the broad anti-inflammatory benefits of the omega-3s. The omega-3s are part of the body’s natural pathways for making a variety of powerful anti-inflammatory substances, including prostaglandin E3, resolvins, and protectins. Studies have found the omega-3s helpful in autoimmune diseases, such as MS, as well as in such GI disorders as Crohn’s disease.^{29 30 31 32}

Try: 1 to 5 grams daily.

It’s not always easy to sift through one’s symptoms, eating habits, and overall lifestyle to establish definitive links between autoimmune diseases (e.g., rheumatoid arthritis, MS, or lupus) or other inflammatory diseases and leaky gut syndrome. Often, an open-minded physician can be helpful.

Whether you’re suffering from an autoimmune disorder or other inflammatory disease—or just want to maintain excellent health—it only makes sense to give your digestive tract a lot of TLC. An integrated approach should focus on three areas:

1. Dietary changes, such as avoiding gluten-containing foods or adopting an elimination diet to identify specific food sensitivities; 

2. Helpful supplements to support gut health; and

3. Lifestyle changes, such as good sleep habits and stress reduction, to reduce the damaging effects of cortisol (the key stress hormone) on the digestive tract.

References

1. http://www.scientificamerican.com/article/among-trillions-of-microbes-in-the-gut-a-few-are-special/
2. Rapin JR, Wiernsperger N. Possible links between intestinal permeability and food processing: A potential therapeutic niche for glutamine. Clinics (Sao Paulo). 2010 Jun;65(6):635-43.
3. Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiotia promoting colitis and metabolic syndrome. Nature, 2015 https://doi.org/10.1038/nature14232
4. Fasano A, Not T, Wang W, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet, 2000;355:1518–1519.
5. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol, 2012;10:1096-100.
6. Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci, 2012;1258:25-33.
7. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev, 2011;91:151-175.
8. Tripathi A, Lammers KM, Goldblum S, et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A, 2009;106:16799-804.
9. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol, 012;42:71-78.
10. Karakuła-Juchnowicz H, Szachta P, Opolska A, et al. The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders. Nutr Neurosci, 2014: epub ahead of print.
11. Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, Zetoune FS, Andjelkovic AV, Fasano A, Ward PA. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. Am J Physiol Lung Cell Mol Physiol, 2013;304:L863-L872.
12. Mansueto P, Seidita A, D'Alcamo A, et al. Non-celiac gluten sensitivity: literature review. J Am Coll Nutr, 2014;33:39-54.
13. Parent ratings of behavioral effects of biomedical interventions. Autism Research Institute publication #34, March 2009. http://www.autism.com/pdf/providers/ParentRatings2009.pdf
14. http://www.scientificamerican.com/article/gut-bacteria-may-play-a-role-…
15. Munger KL, Köchert K, Simon KC, et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Transl Neurol, 2014 Aug;1(8):605-617.
16. Santos Rocha C, Lakhdari O, Blottière HM, et al. Anti-inflammatory properties of dairy lactobacilli. Inflamm Bowel Dis. 2012 Apr;18(4):657-66.
17. Del Piano M, Anderloni A, Balzarini M, et al. The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to restore the “gastric barrier effect” in patients chronically treated with PPI: a pilot study. J Clin Gastroenterol, 2012;46 Suppl:S18-26
18. Dylag K, Hubalewska-Mazgaj M, Surmiak M, et al. Probiotics in the mechanism of protection against gut inflammation and therapy of gastrointestinal disorders. Curr Pharm Des. 2014;20(7):1149-1155.
19. Feizizadeh S, Salehi-Abargouei A, Akbari V. Efficacy and safety of Saccharomyces boulardii for acute diarrhea. Pediatrics, 2014 Jul;134(1):e176-91
20. Veiga P, Pons N, Agrawal A, et al. Changes of the human gut microbiome induced by a fermented milk product. Scientific Reports, 2014: doi 10.1038/srep06328.
21. Marchbank T, Davison G, Oakes JR, et al. The nutraceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G477-84.
22. Shive W, Snider RN, Dubilier B, et al. Glutamine in treatment of peptic ulcer; preliminary report. Texas State Journal of Medicine, 1957Nov;53(11):840-842.
23. Ann JY, Kim SJ, Han SP, et al. Effect of glutamine on the non-steroidal anti-inflammatory drug-induced bacterial translocation. Korean J Gastroenterol, 2004;44:252-258.
24. Grigorian A, Araujo L, Naidu NN, et al. N-acetylglucosamine inhibits T-helper 1 (Th1)/T-helper 17 (Th17) cell responses and treats experimental autoimmune encephalomyelitis. J Biol Chem, 2011 Nov 18;286(46):40133-40141.
25. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.
26. Kuo SM. The interplay between fiber and the intestinal microbiome in the inflammatory response. Adv Nutr. 2013 Jan 1;4(1):16-28.
27. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A, 2008 Oct 28;105(43):16731-16736.
28. http://www.scientificamerican.com/article/among-trillions-of-microbes-i…
29. Belluzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med. 1996 Jun 13;334(24):1557-60.
30. Chen S, Zhang H, Pu H, et al. n-3 PUFA supplementation benefits microglial responses to myelin pathology. Sci Rep. 2014 Dec 12;4:7458. doi: 10.1038/srep07458.
31. Adamo AM. Nutritional factors and aging in demyelinating diseases. Genes Nutr. 2014 Jan;9(1):360. doi: 10.1007/s12263-013-0360-8.
32. Ramirez-Ramirez V, Macias-Islas MA, Ortiz GG, et al. Efficacy of fish oil on serum of TNF α , IL-1 β , and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxid Med Cell Longev. 2013;2013:709493. doi: 10.1155/2013/709493.
33. Spielman, L.J., Gibson, D.L., Klegeris, A. (2018). Unhealthy gut, unhealthy brain: the role of the intestinal microbiota in neurodegenerative diseases. Neurochem Int, 120, 149-163. https://doi.org/10.1016/j.neuint.2018.08.005
34. Farhadi, A., Banan, A., Fields, J., Keshavarzian, A. (2003). Intestinal barrier: an interface between health and disease. J Gastroenterol Hepatol, 18, 479-497. https://doi.org/10.1046/j.1440-1746.2003.03032.x
35. Intestinal permeability & associated diseases. The Institute for Functional Medicine. (2019, December 15). Retrieved September 30, 2021, from https://www.ifm.org/news-insights/gut-intestinal-permeability-associated-diseases/
36. de Kort, S., Keszthelyi, D., & Masclee, A. A. (2011). Leaky gut and diabetes mellitus: what is the link?. Obesity reviews : an official journal of the International Association for the Study of Obesity, 12(6), 449–458. https://doi.org/10.1111/j.1467-789X.2010.00845.x