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Why intestinal permeability causes so much harm, and what to do about it
Brilliantly packed within the body, the intestinal barrier covers a surface area of over 4,000 square feet and requires about 40% of the body’s energy expenditure. But what happens when it starts to break down?
What is leaky gut?
Hold up your hands and interlace them so the fingers of your left hand slip between the fingers of your right. Wiggle your hands closer together, so there are no visible gaps between your hands. You’ve just created a model of the digestive tract.
What would happen if you poured some beans into the palms of your hands while they were locked together like this? Probably nothing: you’d just have a handful of legumes. But what if you pulled your hands slightly apart, so there were some spaces between your fingers? It would rain beans, your floor would be a mess, and you’d likely become flustered with this learning activity.
Our digestive tracts aren’t all that different, with the cells lining the gut nestled closely together, reinforced by something called tight junctions. The gut serves as a protective barrier, keeping that which we swallow from jumping right into the bloodstream. Good gut integrity prevents water and electrolytes from leaking out of circulation, and blocks toxins and microorganisms from sneaking in. The little “cracks” between the cells, however, allow for the absorption of dietary nutrients that are broken down into very small molecules by digestive enzymes, bile, stomach acid, and the action of the microbes in our gut.[1],[2]
But when the gut lining becomes compromised, the spaces between the cells grow, much like the spaces between our fingers when we pull our hands apart. This describes a state known as increased intestinal permeability – or “leaky gut,” as it’s more commonly called.[3]
And like the storm of beans raining down on the kitchen floor between our “leaky” fingers, trouble ensues when intestinal permeability is compromised. Like the beans between our fingers, bacteria, toxins, undigested food, and other waste can “leak” out of the digestive tract, through the cracks in the gut lining, and into the body. These invaders can then make their way into the bloodstream, triggering the types of immune reactions and inflammation implicated in such conditions as ulcerative colitis, Crohn’s disease, celiac disease, food allergies, irritable bowel syndrome (IBS), and even obesity and cardiovascular disease.[4],[5]
What causes leaky gut, and what can be done to treat it?
Zonulin is an inflammatory protein that helps regulate gut “leakiness” by opening and closing the spaces between cells lining the digestive tract.[6] Altered zonulin expression has been associated with autoimmune diseases, inflammatory conditions, and cancer.[7] Zonulin is upregulated in several autoimmune diseases, and seems to precede their onset, likely contributing to their development.[8],[9],[10],[11],[12] Gastrointestinal infections have also been shown to increase the production of zonulin, accompanied by altered tight junction integrity. Even diet plays a role, with gluten – the protein found in the endosperm of wheat, barley, and rye – being particularly harmful to the gut lining vis-Ă -vis zonulin expression.[13] Avoiding gluten may therefore be a powerful way to improve intestinal integrity. Digestive aids such as digestive enzymes, pancreatic glandular substances,[14] or supplemental bile[15] may also alleviate the stress on the digestive system by breaking down dietary substances more completely.
Altered zonulin expression has been associated with autoimmune diseases, inflammatory conditions, and cancer.
Infections. Lipopolysaccharide, or LPS, is the major component of the outer membrane of gram-negative bacteria. LPS is also an endotoxin, which, as the name implies, is toxic to us humans. As an endotoxin, LPS activates many types of infection-fighting cells in the human body, creating inflammation and thus harming the gut lining.[16],[17] The body’s reaction to LPS allows the endotoxin to transfer through into circulation, triggering a systemic immune response, creating further inflammation, and taxing the liver and kidneys.[18],[19] This damage contributes to a variety of diseases, including depression,[20] chronic fatigue syndrome,[21] liver disease,[22] heart disease,[23] obesity,[24] and even infertility.[25] Intestinal infections can also degrade intestinal integrity through methods other than the generation of LPS,[26] making natural agents that prevent and treat infections – such as berberine – important in the prevention and management of leaky gut.
Dysbiosis. A shift in the microbial milieu of the gut can alter the ratio of helpful to harmful bacteria. This state, known as dysbiosis, has been implicated with a host of ailments, from obesity to asthma to even depression.[27],[28],[29] Formula-fed babies are also more likely to develop leaky gut later in life than their breastfed peers, in large part due to the positive influences of breast milk on the microbiome.[30] Colostrum, the milk secreted during the first days after a female gives birth, has high levels of many growth factors helpful for the digestive tract, and may therefore be an effective strategy in healing leaky gut.[31],[32] Colostrum also contains lactoferrin, which has broad antimicrobial action and can also be used strategically to bind endotoxin.[33]
In addition to antibiotics, certain medications have also been implicated with dysbiosis and leaky gut. In particular, stomach acid-suppressing medications like proton-pump inhibitors (PPIs)[34] and non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to have adverse effects on the microbiome and gut integrity.[35],[36],[37] The value of a carefully-formulated probiotic supplement in restoring microbial balance thus cannot be overstated, whether in adults, elders, or children. Berberine, the active constituent in Oregon grape root and goldenseal, also improves microbial balance, in addition to reducing intestinal permeability and tonifying motility.[38],[39],[40],[41]
Nutritional Influences. Diets low in fiber[42] and high in saturated fat,[43] sugar,[44] and processed foods[45] all contribute to leaky gut, as does alcohol consumption.[46],[47] Nutritional deficiencies – namely zinc,[48],[49] vitamin A,[50] and vitamin D3[51],[52],[53] – can also lead to increased intestinal permeability. L-glutamine supports the integrity of tight junctions and is the preferred “fuel” for the rapidly-proliferating cells of the intestinal mucosa, which regenerate every 3-5 days.[54] Supplementing these nutrients may therefore improve gut integrity.
Nutritional deficiencies – namely zinc, vitamin A, and vitamin D3 – can also lead to increased intestinal permeability.
Additional agents that support healing of the gut mucosa include slippery elm,[55] N-acetyl-D-glucosamine (NAG), and hydrolyzed collagen. Phosphatidylcholine (PC), a critical component of the protective mucus layer in the gut,[56] and butyrate, an anti-inflammatory short-chain fatty acid produced by healthy bacteria in the gut, also play an important role in healing leaky gut.[57]
Other causes of leaky gut include chronic stress,[58],[59] the aging process,[60] traumas such as burns or injury,[61],[62] inflammation,[63],[64] radiation,[65] and chemotherapy.[66] Strategies to help the body cope with stress, fight inflammation, reverse oxidative stress, and heal from injuries may all therefore be helpful.
Hope for healing
Through a healthy diet, lifestyle modifications, and mindfully chosen natural agents, there is hope for healing leaky gut. By supporting the integrity of the digestive tract, we are better able to protect ourselves against autoimmune disease, allergies, cancer, and host of other ailments. Read on in our second post on this topic to learn more about the nutritional tools that can help resolve leaky gut.
Click here to see References
[1] Brandtzaeg P. The gut as communicator between environment and host: immunological consequences. Eur J Pharmacol. 2011 Sep; 668 Suppl 1():S16-32.
[2] Hooper LV, et al. Interactions between the microbiota and the immune system. Science. 2012 Jun 8; 336(6086):1268-73.
[3] Visser J, et al. Tight junctions, intestinal permeability, and autoimmunity. Ann NY Acad Sci 2009;1165:195-205.
[4] Bischoff SC, et al. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014 Nov 18;14:189.
[5] Teixeira TF, et al. Potential mechanisms for the emerging link between obesity and increased intestinal permeability. Nutr Res. 2012 Sep;32(9):637-47.
[6] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.
[7] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75.
[8] El Asmar R, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002 Nov;123(5):1607-15.
[9] Sapone A, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9.
[10] Clemente MG, et al. Immune reaction against the cytoskeleton in coeliac disease. Gut. 2000 Oct;47(4):520-6.
[11] Pedreira S, et al. Significance of smooth muscle/anti-actin autoantibodies in celiac disease. Acta Gastroenterol Latinoam. 2005;35(2):83-93.
[12] Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258:25-33.
[13] Drago S, et al. Gliadin, zonulin and gut permeability: effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scandinavian Journal of Gastroenterology 2006;41:408-419.
[14] Leeds JS, et al. Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency. Clin Gastroenterol Hepatol. 2010 May;8(5):433-8.
[15] Abrahamsson H, et al. Altered bile acid metabolism in patients with constipation-predominant irritable bowel syndrome and functional constipation. Scand J Gastroenterol. 2008;43(12):1483-8.
[16] Alexander C, Rietschel ET. Bacterial lipopolysaccharides and innate immunity. J Endotoxin Res. 2001;7(3):167-202
[17] Heumann D, Roger T. Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta. 2002 Sep;323(1-2):59-72.
[18] Zinchuk V, Zinchuk O, Okada T. Experimental LPS-induced cholestasis alters subcellular distribution and affects colocalization of Mrp2 and Bsep proteins: a quantitative colocalization study. Microsc Res Tech. 2005 Jun 1;67(2):65-70.
[19] Cani PD, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72.
[20] Maes M, et al. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.
[21] Maes M, et al. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.
[22] Bode C, Bode JC. Activation of the innate immune system and alcoholic liver disease: effects of ethanol per se or enhanced intestinal translocation of bacterial toxins induced by ethanol? Alcohol Clin Exp Res. 2005 Nov;29(11 Suppl):166S-71S.
[23] Sandek A, et al. The emerging role of the gut in chronic heart failure. Curr Opin Clin Nutr Metab Care. 2008 Sep;11(5):632-9.
[24] Piya MK, et al. Metabolic endotoxaemia: is it more than just a gut feeling? Curr Opin Lipidol. 2013 Feb;24(1):78-85.
[25] Tremellen K, et al. Metabolic endotoxaemia – a potential novel link between ovarian inflammation and impaired progesterone production. Gynecol Endocrinol. 2015 Apr;31(4):309
[26] J Berkes, et al. Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut. 2003 Mar; 52(3): 439-451.
[27] Azad MB, et al. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013 Mar 19;185(5):385-94.
[28] John R. Kelly, et al. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015; 9: 392.
[29] Sunil T, et al. The host microbiome regulates and maintains human health: a primer and perspective for non-microbiologists. Cancer Res. 2017 Apr 15; 77(8): 1783-1812.
[30] Le Huërou-Luron I, et al. Breast- v. formula-feeding: impacts on the digestive tract and immediate and long-term health effects. Nutr Res Rev. 2010 Jun;23(1):23-36.
[31] Playford RJ, et al. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders. Am J Clin Nutr. 2000 Jul;72(1):5-14.
[32] Playford RJ, et al. Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability. Clin Sci (Lond). 2001 Jun;100(6):627-33.
[33] Gifford JL, et al. Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell Mol Life Sci. 2005 Nov;62(22):2588-98
[34] van Vlerken LG, et al. Bacterial infections in cirrhosis: role of proton pump inhibitors and intestinal permeability. Eur J Clin Invest. 2012 Jul;42(7):760-7.
[35] Bjarnason I, Takeuchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. J Gastroenterol. 2009;44 Suppl 19:23-9.
[36] Tugendreich S, et al. NSAID-induced acute phase response is due to increased intestinal permeability and characterized by early and consistent alterations in hepatic gene expression. Toxicol Pathol. 2006;34(2):168-79.
[37] Bjarnason I, et al. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology. 1993 Jun;104(6):1832-47.
[38] Wang Y, et al. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. Metabolism. 2017 May;70:72-84.
[39] Li N, et al. Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells. Eur J Pharm Sci. 2010 Apr 16;40(1):1-8.
[40] Wang Y, et al. Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism. Metabolism. 2017 May;70:72-84.
[41] Feng Y, et al. Inhibiting roles of berberine in gut movement of rodents are related to activation of the endogenous opioid system. Phytother Res. 2013 Oct;27(10):1564-71.
[42] Qinghui Mu, et al. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017; 8: 598.
[43] Pendyala S, et al. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology. 2012 May; 142(5):1100-1101.e2.
[44] Stephan C Bischoff, et al. Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol. 2014; 14: 189. Published online 2014 Nov 18.
[45] Chassaing B, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature. 2015 Mar 5;519(7541):92-6.
[46] Vishnudutt Purohit, et al. Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences (Summary of a Symposium). Alcohol. 2008 Aug; 42(5): 349-361.
[47] Bjarnason I, et al. The leaky gut of alcoholism: possible route of entry for toxic compounds. Lancet. 1984 Jan 28;1(8370):179-82.
[48] Manary MJ, et al. Perturbed zinc homeostasis in rural 3-5-y-old Malawian children is associated with abnormalities in intestinal permeability attributed to tropical enteropathy. Pediatr Res. 2010 Jun;67(6):671-5.
[49] Miyoshi Y, et al. Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression. Am J Physiol Gastrointest Liver Physiol. 2016 Jul 1;311(1):G105-16.
[50] Amit-Romach E, et al. Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet. J Nutr Biochem. 2009 Jan;20(1):70-7.
[51] Assa A, et al. Vitamin D deficiency promotes epithelial barrier dysfunction and intestinal inflammation. J Infect Dis. 2014 Oct 15;210(8):1296-305.
[52] Kong J, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16.
[53] Kong J, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol. 2008 Jan;294(1):G208-16.
[54] Foitzik T, et al. Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis. J Gastrointest Surg. 1997 Jan-Feb;1(1):40-6.
[55] Misra S. Integrative therapies and pediatric inflammatory bowel disease: the current evidence. Children (Basel). 2014 Sep; 1(2): 149-165.
[56] Stremmel W, et al. Mucosal protection by phosphatidylcholine. Dig Dis. 2012;30 Suppl 3:85-91.
[57] Bloemen JG, et al. Butyrate enemas improve intestinal anastomotic strength in a rat model. Dis Colon Rectum 2010 Jul;53(7):1069-1075.
[58] Overman EL, et al. CRF induces intestinal epithelial barrier injury via the release of mast cell proteases and TNF-α. PLoS One. 2012;7(6):e39935.
[59] Rodiño-Janeiro BK, et al. Role of Corticotropin-releasing Factor in Gastrointestinal Permeability. J Neurogastroenterol Motil. 2015 Jan 1;21(1):33-50.
[60] Qi Y, et al. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging. J Am Med Dir Assoc. 2017 Sep 1;18(9):810.e1-810.e4.
[61] Earley ZM, et al. Burn injury alters the intestinal microbiome and increases gut permeability and bacterial translocation. PLoS One. 2015 Jul 8;10(7):e0129996.
[62] Faries PL, et al. Intestinal permeability correlates with severity of injury in trauma patients. J Trauma. 1998 Jun;44(6):1031-5; discussion 1035-6.
[63] Al-Sadi R, et al. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci. 2009 Jan 1; 14: 2765-2778.
[64] Ma TY, et al. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G367-76.
[65] Nejdfors P, et al. Intestinal permeability in humans is increased after radiation therapy. Dis Colon Rectum. 2000 Nov;43(11):1582-1587; discussion 1587-8.
[66] Daniele B, et al. Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer. J Clin Gastroenterol. 2001 Mar;32(3):228-30.
The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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Dr. Erica Zelfand
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