Increased Gut Permeability – Causes & Consequences
Those of you who have been following this blog know I’m interested – for personal reasons and also just because it’s fascinating – in how the state of the probiotics in our gut microbiomes affects our health in general. So this development is of great interest to me: A different kind of PREbiotic dietary supplement, Good Gut Daily, has recently entered the market. PREbiotics provide the nourishment for our PRObiotics. This kind is polyphenol-based and has been clinically shown to calm acute digestive symptoms in as little as 30 minutes and enhance immune health. For those of you who, like me, suffer from ongoing digestive health problems and haven’t found a satisfactory solution, the arrival of this new supplement is excellent news. Polyphenols are naturally occurring compounds found in plants – including fruits, vegetables, tea, coffee, and wine. I’ll be writing about Good Gut Daily in more depth in an upcoming post but, in the interest of not overwhelming you with information, I thought it useful to do a preliminary post on some of the causes of increased intestinal leakiness so you can see how your GI problems originated and how poor gut health creates major health problems elsewhere in your body. This post grew out of a phone and email conversations with molecular biologist Rob Wotring, the Chief Scientific Officer at Greenteaspoon. Many thanks, Rob, for sharing some of your wealth of information on how the gut works. DIGESTION – FROM MOUTH TO ANUS
The human digestive tract runs from the mouth at the top to the anus at the other end. Foreign matter (food) is taken in and partially broken down by chewing in the mouth. It then travels down through the esophagus to the stomach and from there into the small and large intestines, where it is selectively digested. During this trip, various phases of digestion take place and nutrients are extracted and absorbed. The liver, gall bladder and pancreas, organs that aid in the digestive process, are located along the length of the GI tract. The total length of the GI tract varies from person to person. In an adult male the range is 20 to 40 feet. On average, the small intestine in adults is 22 feet long and the large intestine is 5 feet. As you can intuit, a lot could go wrong during that long trip – and much of that depends on the quality of what you deliver to your mouth as ‘food’.
You can see the location of the mucosal layer (called ‘mucous coat’ in the diagram below) and the intestinal villi in this cross-section of the human small intestine. The empty space in the center, just below the villi (the spikes you see in the image of a healthy mucosal membrane in the image to the left above), is called the lumen, the tube in which food travels through the intestines.
INCREASED GUT PERMEABILITY – AKA LEAKY GUT Increased gut permeability – also known as hyper-permeable intestines or “leaky gut” – describes the intestinal lining’s having become more porous than it should be so the process of what is allowed out into the body no longer functions properly. Larger, undigested food molecules and other bad things (such as yeasts, toxins, and other forms of waste that normally would continue on and get excreted through the anus) flow freely through these too-large holes in the intestinal lining and enter the bloodstream, where they don’t belong and are treated as dangerous invaders. The gut’s mucosal layer is thin, delicate – and very important. This is where our probiotic bacteria live, so degrading it also degrades the strength of our immune systems. The probiotics residing in the gut mucosal layer make up 70-90% of the human immune system. Damage to the gut’s mucosal layer leads to a whole range of serious problems as the body tries to cope with the invaders being released into the bloodstream. Once this lining has become disturbed, allowing problematic things to flow through it into the blood stream, a cycle of chronic irritation begins, leading to chronic inflammation in the body and a whole series of autoimmune conditions. For an easy to understand explanation of increased gut permeability, see Leaky Gut Syndrome in Plain English – and How to Fix It. (Reasoner, undated)
Symptoms associated with Leaky Gut Syndrome (Age Management & Hormone Balance Center, 2013)
Abdominal Pain (chronic)
Gluten Intolerance (celiac)
Multiple Chemical Sensitivities
Poor Exercise Tolerance
Recurrent Vaginal Infections
Swollen Lymph Glands
Constant Hunger Pains
Shortness of Breath
Fears of unknown origin
Recurrent Bladder Infections
Recurrent Skin Rashes
Here’s a partial list of diseases and conditions associated with increased intestinal permeability (Galland, undated) (Age Management & Hormone Balance Center, 2013):
Chronic arthritis/pain treated with NSAIDS
Chronic Fatigue Syndrome
Food Allergies & intolerances
Inflammatory bowel disease & syndrome
Multiple food & chemical sensitivies
Neoplasia treated with cytotoxic drugs
Pancreatic dysfunction & insufficiency
There are other chronic diseases and conditions we now know are also autoimmune in nature – including allergies, diabetes, lupus, multiple sclorosis, myesthenia gravis, endometriosis, some heart conditions, juvenile arthritis, chronic Lyme disease, myasthenia gravis, PANDAS, PCOS, pernicious anemia, Raynaud’s, restless leg syndrome, rheumatic fever, rheumatoid arthritis, some thyroid disease, vitiligo … and many others. Learn more about AUTOIMMUNE DISORDERS.
Ten years ago the father of integrative medicine, Dr Andrew Weil, offered this definition of leaky gut (Weil, 2005): Leaky gut syndrome is not generally recognized by conventional physicians, but evidence is accumulating that it is a real condition that affects the lining of the intestines. The theory is that leaky gut syndrome (also called increased intestinal permeability), is the result of damage to the intestinal lining, making it less able to protect the internal environment as well as to filter needed nutrients and other biological substances. As a consequence, some bacteria and their toxins, incompletely digested proteins and fats, and waste not normally absorbed may “leak” out of the intestines into the blood stream. This triggers an autoimmune reaction, which can lead to gastrointestinal problems such as abdominal bloating, excessive gas and cramps, fatigue, food sensitivities, joint pain, skin rashes, and autoimmunity. The cause of this syndrome may be chronic inflammation, food sensitivity, damage from taking large amounts of nonsteroidal anti-inflammatory drugs (NSAIDS), cytotoxic drugs and radiation or certain antibiotics, excessive alcohol consumption, or compromised immunity.
FUNCTIONS OF THE INTESTINAL MUCOSAL LAYER (Camp, 2015) This thin, wet layer lining the intestinal walls serves many important functions:
Determines which nutrients pass through the intestinal walls and into the blood stream
Protects and covers mast cells that contain histamines
Secretes antibodies made from the intestinal wall to support immune defenses
Prevents yeast and parasites from adhering to the intestinal wall
All of these factors can lead to breakdown of the tight junctions and leaky gut. NSAIDs are pain relievers like Aspirin, Aleve, Advil, etc. SIBO is an acronym for small intestinal bacterial overgrowth. Additionally, low exercise levels is a stressor under the category of physical stress. CAUSES OF INCREASED GUT PERMEABILITY INFECTIONS THAT PENETRATE THE GUT’S MUCOSAL LAYER Infections (eg, acute viral or bacterial infection, intestinal parasites, HIV, candida, etc) that damage the integrity of the intestinal mucosal lining are the most common causes of increased gut permeability. (Galland, undated) (Wotring, 2015)
Ulcerative means a loss of the surface lining. Colitis means inflammation of the mucosa lining inside the colon’s walls. Ulcerative colitis occurs when the immune system reacts aggressively against the normal bacteria inhabiting the colon – ie, it is an autoimmune process.
The gut’s mucosal lining in babies under six months is not yet fully formed. (Wotring, 2015) Mature intestines are made to allow absorption of appropriate nutrients while also preventing pathogens and toxins from entering the body and causing diseases. In young babies, the barrier function is underdeveloped so large amounts of big molecules get through the gut mucosal layer and enter circulation in the body. This makes infants susceptible to infectious diarrhea, necrotizing enterocolitis (the lining of the intestinal wall dies and the tissue falls off), and allergic gastroenteropathy. Since intestinal barrier dysfunction is known to predispose the development of intestinal diseases as well as autoimmune diseases in other parts of the body, it is highly important that infants’ intestinal barriers be allowed to receive the health benefits of breast milk so they mature properly. Illnesses associated with intestinal barrier dysfunction occur more often in adults who were formula-fed as infants than in those who were nursed. (Anderson et al, 2012) In the elderly, epithelial stem cells mutate more frequently, leading to thinning of the mucosal lining. GI disorders are a major cause of illness and death for the elderly. (Saffrey, 2013) (Wotring, 2015) REDUCED OXYGEN-CARRYING CONDITIONS
Ailments that reduce the amount of oxygen carried in the blood – eg, anemia, heart conditions, respiratory problems – are associated with increased gut permeability. (Wotring, 2015) The observation that gut and lung disorders commonly occur together has led GI and respiratory researchers to think they share a common cause. For example, asthmatic flares and seasonal allergic reactions – both autoimmune conditions – are accompanied by inflammation in the digestive tract. In a 2010 paper appearing in the National Review of Gastroenterology and Hepatology, neurogastroenterologist Nicholas Talley and his colleagues observed that people with asthma and allergic rhinitis have abnormally high levels of eosinophils in both their airways and their intestines. In healthy people, these cells aren’t found in their airways at all. Eosinophils are specialized cells in the immune system created in the bone marrow. In the mucous membrane lining the stomach, small intestine and colon, their purpose is to prevent pathogenic bugs and toxins from escaping through the gut walls and getting into the body. In allergies, these eosinophilic cells start growing in the lungs and airways and the ones in the GI tract stop serving their protective function and instead damage the gut’s mucosal lining, allowing toxins to leak through. This increased intestinal permeability has often been documented in asthma patients. (Johnson, 2010) ALCOHOL
Alcohol disrupts the integrity of the gut’s mucosal layer. The disruption can be measured within 30 minutes after alcohol has been consumed. (Wotring, 2015) Alcohol damages the delicate lining of the stomach and intestinal tract as it passes through, creating increased permeability. This increased porosity permits large, incompletely digested food particles to move through the gut walls directly into the bloodstream, where immune cells regard them as foreign invaders and attack them with specially designed antibodies. Once these antibodies have been created, they remain in the body on the look out for offending food particles to come along, creating a vicious cycle of autoimmunity: Because the alcoholic’s gut lining has become too permeable, improperly digested particles are always invading and a perpetual allergy-addiction cycle has been created – the immune system is in a state of continual hyper-reactivity. Several studies have shown that alcoholic patients have an unusually high degree of allergic responses: both to “classic” allergens such as pollen and to various foods. Multiple studies have compared the allergic responses of alcoholics, depressive, and schizophrenic patients, and found that the alcoholic group was significantly more allergic to a variety of food allergens. A similar study compared patients admitted to an inpatient alcoholism hospital with a matched control group of patients with no history or evidence of alcohol abuse who have been admitted to a general hospital for elective surgery. Most alcoholics are allergic to a wide range of foods as well as environmental-mental allergens. Among foods, grains (the primary ingredient of many alcoholic beverages) are highly reactive. It is well known that particular foods and/or certain chemicals-can become an addiction. – (Occhipinti, 2013) DIETARY EMULSIFIERS
Emulsifiers are chemicals or natural substances that encourage the suspension of one type of liquid in another – as in the oil and water in margarine, shortening, ice cream, salad dressings, and creamy sauces. They are one of the most frequently used type of food additive. Emulsifiers are added to commercial breads and cakes, icings, frozen desserts, soups, mayonnaise, homogenized milk, whipped toppings, non-dairy creamers, chocolate bars, chew candies, bubble gum, extruded snacks, soft drinks, bottled liquid coffees … and many other processed foods. (FoodAdditivesWorld, 2013) Emulsifiers are also added to cosmetics, lotions, and some pharmaceuticals for the same reason they’re put into processed foods – they improve product appearance by preventing ingredients from separating and extend storage life. (Encyclopedia Britannica, 2015) The FDA and other regulatory agencies in the US claim there is no evidence that chemical emulsifiers increase the risk of cancer or have other toxic effects in mammals so have ruled they are “generally regarded as safe” (GRAS) for use in processed foods.
Yet there is evidence that these emulsifiers disturb the colonies of probiotic bacteria living in the colon, increasing the risk of inflammatory bowel diseases and metabolic disorders. (Reardon, 2015)
Yet there is evidence that these emulsifiers disturb the colonies of probiotic bacteria living in the colon, increasing the risk of inflammatory bowel diseases and metabolic disorders. (Reardon, 2015) Anything that can break down fats also breaks down the gut’s mucosal layer. (Wotring, 2015) Could adding emulsifiers to food products to make them look more appealing and ‘last’ longer possibly be worth ruining our gut linings and increasing our risk for developing one or more autoimmune diseases?
See Emulsifiers for more than you might want to know about these food additives. NSAIDS
Aspirin, ibuprofen and naproxin are common NSAIDs (non-steroidal anti-inflammatory drugs) available OTC for use as pain relievers. NSAIDs are also available at prescription strength. They are the most widely prescribed medications in the US. 100 million Americans use them regularly to manage pain. ALL NSAIDs cause injury in the GI tract: erosions, ulcers, bleeding and perforations in the stomach and intestines. An estimated 16,500 Americans die each year from and 100,000 are hospitalized with NSAID-induced complications. (PLx, undated)
It takes NSAIDs such as asprin, ibuprofen, Advil, Motrin, Aleve only 15-30 minutes to create lesions in the mucosal layer of the GI tract! (Wotring, 2015) NSAIDs damage the hormones in your GI tract that protect the gut from becoming inflamed. Chronic use can lead to dire consequences such as intestinal perforations, H. pilori infection, kidney failure, Crohn’s disease, diverticular disease, inflammatory bowel disease. (Alice, 2015) (Camp, 2015) Japanese researchers found small bowel injuries occurring in 80% of their study participants after only two weeks on aspirin therapy. Other studies have noted GI damage in people on low-dose aspirin therapy taken for cardiovascular protection. (Alice, 2015).
After many decades of promoting an aspirin a day to prevent heart attacks, the FDA has now reversed its position. (Alice, 2015) The FDA’s website now says: “FDA has concluded that the data do not support the use of aspirin as a preventive medication by people who have not had a heart attack, stroke or cardiovascular problems, a use that is called ‘primary prevention.’ In such people, the benefit has not been established but risks — such as dangerous bleeding into the brain or stomach — are still present.” Hopefully this news will change the behavior of the 40 million Americans who take an aspirin every day. See this WebMD article for more information on both OTC and prescription NSAIDs. INTENSE EXERCISE
Many people experience nausea, heartburn, cramping, and diarrhea while exercising – especially during high-intensity exercise. When the body is at rest, your heart directs 20-25% of its pumped blood to your digestive tract. While even moderate exercise increases your heart rate and therefore the amount of blood being pumped from your heart, the amount of blood flowing to the GI tracts gets decreased by as much as 60-70% and is instead diverted to your muscles, heart, lungs, and brain. Increasing the intensity of your workout reduces the blood flow to the gut even further. This decrease causes those common GI complaints. (Rocky Mountains Health Plans, 2014) The harder or longer you run or exercise, the less blood gets delivered to your gut, causing digestion to slow. (Powell, 2013) Runners, cyclists and triathletes tend to get diarrhea after 30-60 minutes of intense exercise. These athletes often put toilet paper inside the seat of their pants to soak up the mess. (Wotring, 2015)
Even worse, exercising can damage the gut’s mucosal lining and cause increased gut permeability. The authors of an article in the Journal of the International Society of Sports Nutrition explain how this works: Among athletes strenuous exercise, dehydration and gastric emptying … delay are the main causes of gastrointestinal (GI) complaints …. A serious underperfusion of the gut often leads to mucosal damage and enhanced permeability so as to hide blood loss, microbiota invasion (or endotoxemia) and food-born allergen absorption (with anaphylaxis)…. Anyone who participates in physical exercise is at risk for injury and illness arising from such activity…. There is a very high prevalence of gastrointestinal (GI) complaints during exercise among long-distance runners, triathletes and athletes involved in other types of strenuous long-lasting exercise. These GI complaints occur because of the redistribution of the blood flow, that is shunted from the viscera to skeletal muscle, heart, lung and brain…. The symptoms are often mild and may not even affect performance. Some of the symptoms, however, can be life-threatening, such as blood loss in feces in the hours following the running presented by some marathoners and long-distance triathletes. Damage to the gut and impaired gut function is associated with increased of intestinal permeability after a marathon. Moreover, vigorous exercise (jogging, aerobics, dancing, tennis, bicycling, racquetball, swimming, and skiing) facilities allergen absorption from the GI tract, leading to a food-dependent exercise induces anaphylaxis (FDEIA). (Prado de Oliveira & Burini, 2011
When the body is in an overheated state, some of the blood that normally flows to the intestines gets diverted to the skin and the temperature inside the intestines increases. (Wotring, 2015) This combination damages the intestinal barrier, creating increased intestinal permeability to microbial endotoxins (toxins present inside a bacterial cell that get released when the cell disintegrates), leading to endotoxemia (the presence of endotoxins in the blood). (Lambert, 2008) Severe endotoxemia can lead to shock, hemorhages, and kidney death.
Be careful when exposing yourself to high heat for extended periods of time (eg, while tanning all day at the beach, taking a long sauna, engaging in intense exercise).
In our conversation, Rob Wotring also mentioned these interesting tidbits about the gut:
The gut’s mucosal layer is being created all the time. This may explain why your gut – and the rest of you – can feel awful say in the morning and then good some hours later on in the day.
Approximately 40% of your energy goes toward producing the mucus barrier.
Women are much more susceptible to disruption of the mucosal layer.
Progesterone thickens the gut lining.
There’s convincing evidence that polyphenol PREbiotics (as in Good Gut Daily) are able to heal damage in the gut lining.
Now that you’ve read about the importance of your intestines and what can happen if their walls become damaged, here’s another depiction of the four layers of the intestinal lining in all its amazing complexity (University of Leeds, undated):
The innermost layer, the MUCOSA, is made up of three parts:
A thin EPITHELIAL lining which includes glandular tissue
An underlying layer of loose connective tissue called the LAMINA PROPRIA which provides vascular support for the epithelium and often contains mucosal glands. Products of digestion pass into capillaries here. Lymphoid follicles and plasma cells are also often found here.
And finally, next to the lamina propria, the MUSCULARIS MUCOSA, a thin, double layer of smooth muscle responsible for local movement of the mucosa.
The layer next to the mucosa is the SUBMUCOSA, a loose connective tissue layer containing larger blood vessels, lymphatics, and nerves. It can also contain mucous secreting glands. The layer outside the submucosa is the MUSCULARIS PROPRIA (EXTERNA). There are usually two sub-layers of smooth muscles in the muscularis propria: An inner circular layer and an outer longitudinal layer. The two layers work together to produce peristalsis ((rhythmic waves of contraction) to move food through the gut. The outermost layer is the ADVENTIA (OR SEROSA) consisting of loose connective tissues containing blood vessels, lymphatics, and nerves. This layer is covered by the visceral peritoneum. And here’s another intestinal cross section so you can see the location of these layers in relation to the central intestinal “tube”, the lumen, where the digesting food is working its way through from the stomach to the anus:
REFERENCES Age Management & Hormone Balance Center. (2013). Gastrointestinal Repair (Leaky Gut Syndrome). See: http://www.agemanagementmi.com/services/gastrointestinal-repair-leaky-gut-syndrome/ Alice. (2015). FDA Reverses Its Position on Daily Aspirin Use. See: http://www.healthfreedoms.org/fda-reverses-its-position-on-daily-aspirin-use/ Anderson, R.C. et al. (2012). The Role of Intestinal Barrier Function in Early Life in the Development of Colitis. See: http://cdn.intechopen.com/pdfs-wm/25358.pdf Camp, M. (2015). Digestive Health. See: http://www.drcamphealth.com/digestivehealth.php CISA. (undated). Emulsifiers. See: http://www.chemistryindustry.biz/emulsifiers.html Encyclopedia Britannica. (2015). Emulsifier. See: http://www.britannica.com/EBchecked/topic/186305/emulsifier FoodAdditivesWorld.com. (2013). Emulsifiers. See: http://www.foodadditivesworld.com/emulsifiers.html Galland, L. (undated). LEAKY GUT SYNDROMES: BREAKING THE VICIOUS CYCLE. See: http://www.mdheal.org/leakygut.htm Greenteaspoon. (2015). Good Gut Daily website. See: http://goodgutdaily.com/ Johnson, K. (2010). The Gut-Lung Connection: How Respiratory Disease is Informing Gastrointestinal Research. See: https://katejohnsonmednews.wordpress.com/2010/06/04/the-gut-lung-connection/ Lambert, G. (2008). Intestinal Barrier Dysfunction, Endotoxemia, and Gastrointestinal Symptoms: The ‘Canary in the Coal Mine’ during Exercise-Heat Stress? In Thermoregulation and Human Performance: Physiological and Biological Aspects. (Editor: Marino, F.E.). See: http://www.karger.com/Article/PDF/151550 Occhipinti, M.J. (2013). Alcoholism’s “Leaky Gut” Syndrome. See: http://www.afpafitness.com/research-articles/alcoholisms-leaky-gut-syndrome PLx. (undated). GI-SAFER NSAID TECHNOLOGY & PRODUCT PIPELINE — WITH PLXGUARD. See: http://www.plxpharma.com/prodDev.htm Powell, B. (2013). Nagging Nausea. Trail Runner. See: http://www.trailrunnermag.com/health/race-day-nutrition/489-nagging-nausea Prado de Oliveira, E. & Burin, R.C. (2011). Food-dependent, exercise-induced gastrointestinal distress. Journal of the International Society of Sports Nutrition, 8:12. See: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190328/ Reardon, S. (2015). Food preservatives linked to obesity and gut disease: Mouse study suggests that emulsifiers alter gut bacteria, leading to the inflammatory bowel condition colitis. Nature.com. See: http://www.nature.com/news/food-preservatives-linked-to-obesity-and-gut-disease-1.16984 Reasoner, J. (undated). Leaky Gut Syndrome in Plain English – and How to Fix It. See: http://scdlifestyle.com/2010/03/the-scd-diet-and-leaky-gut-syndrome/ Rocky Mountain Health Plans. (2014). Don’t Let Digestion Interfere with Your Workout. See: http://blog.rmhp.org/2014/01/dont-let-digestion-interfere-with-your-workout/ Saffrey, M.J. (2013). Aging of the mammalian gastrointestinal tract: a complex organ system. AGE. See: http://link.springer.com/article/10.1007%2Fs11357-013-9603-2 University of Leeds, Faculty of Biological Sciences. Four Layers of the Gastrointestinal Tract. See: http://www.histology.leeds.ac.uk/oral/GI_layers.php WebMD. (2015). NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) and Arthritis. See: http://www.webmd.com/osteoarthritis/guide/anti-inflammatory-drugs#1 Weil, A. (2005). What is leaky gut? See: http://www.drweil.com/drw/u/QAA361058/what-is-leaky-gut.html Wotring, R. (2015). Personal communication. © Copyright 2015 Joan Rothchild Hardin. All Rights Reserved.
DISCLAIMER: Nothing on this site or blog is intended to provide medical advice, diagnosis or treatment.
Comments submitted prior to 8/25/2021
Great source of comprehensive info. I learned a lot!