Leaky gut, autoimmunity, and mental health – What are the links? How do we plug the holes?
Marilu Almeida Hunt, Pharm.D., CPh, CIHC, INHC
The gut (a.k.a. digestive tract) is not just a tube that absorbs nutrients and gets rid of waste – it’s a complex alive system that’s a huge foundation of health. And not just gut health, but the overall health of our bodies and minds. We know how important it is to get all of our essential nutrients from food – and this is a big part of what our digestive tract does. Digestion is an issue central to our health. The gut is not only one of our body’s most under-appreciated organ, but also the brain’s most important advisor
When the gut is not working properly, symptoms can appear. Yes, typical gut and abdominal symptoms, but also other seemingly unrelated symptoms. Did you know that allergies, autoimmunity, and mental health have been linked with gut problems?
Let’s look at one gut problem in particular – leaky gut. This literally involves tiny “leaks” in our gut lining that can allow more than just needed nutrients and water into our bodies. Researchers are looking at this, and I want to share the latest with you, as well as give you some helpful strategies to optimize your gut health, for overall health!
What is “leaky gut” linked with?
The “gut” is part of the digestive system, mainly the intestines, which are located in the abdomen. It’s an alive and very complex “tube” that acts as a gateway deciding what will enter the internal circulation of the body, and what must not get by. It digests and absorbs nutrients and water. It prevents toxins and “bad” microbes from being absorbed. And it shuttles all the waste to continue on and be eliminated.
You may think that symptoms of a leaky gut (a.k.a. “intestinal permeability”) are felt in the gut, and you’re right…to a point. Would you be surprised to know that lots of other symptoms and conditions are linked with leaky gut?
Leaky gut has been associated with:
- Autoimmune diseases (e.g. Type I diabetes, celiac disease, etc.)
- Inflammatory Bowel Diseases (e.g. ulcerative colitis, Crohn’s)
- Psychological stress and mental health
- And more!
Researchers are still figuring out the exact role that leaky gut plays in these conditions. Either way, the connections are there, and there are things that you can definitely do to improve your gut health. But first, how is our gut structured, and what can promote it to leak?
Medications: Steroids, over-the-counter painkillers, PPI to reduce stomach acid and antibiotics are just a few of the medications that can contribute to a leaky gut. Taking these types of medications for long periods of time can make this even more likely. With NSAIDs, the gut can become leakier within 24 hours. If you can avoid taking these medications too regularly, it can help to avoid increased gut permeability.
Stress: According to research, stress can increase the potential for a leaky gut. Studies on rats have also shown a strong link between stress and intestinal permeability. Keeping stress levels under control is super important for reducing potential for a leaky gut.
Intense exercise: Regular exercise can be super important for keeping your gut healthy but there’s a fine balance. Strenuous exercise can have the opposite effect and increase the potential for a leaky gut.
Several studies have shown a link between exercising intensely and increased intestinal permeability, even for athletes. In a study involving cyclists, exercising at 70% maximum capacity led to a “leakier” gut and more food proteins entering the bloodstream. Moderate exercise is a great move for a healthy gut barrier. Just don’t overdo things!
Gut structure – Three layers of our gut lining
Our guts have a three-layer lining that helps to allow things we need in, and keep harmful things out.
The first (outermost) layer is just one-cell thick. It’s a barrier that absorbs the nutrients and water we need, and physically prevents undigested compounds, toxins, and bacteria from getting in. Laid out flat, this layer makes up the largest surface area between the internal circulation of our bodies and the outside world (i.e. what we eat and drink).
This layer has at least seven different types of cells, and 90% of them are one type called “enterocytes.” These enterocytes actively absorb what we need and keep out what we don’t. They also help to create and regulate the other two layers.
FUN FACT: Most enterocytes are replaced with new ones every 3-5 days or so.
Enterocytes are held together with different types of bonds. The one most studied is called a “tight junction.” These tight junctions are made up of several types of protein. When they loosen, it creates tiny holes (or permeations) in this first layer since the cells are not “stuck” together as much as they should be.
The second layer is mucus. This mucus provides physical separation between the outermost enterocyte layer and the microbes and food that are inside the centre, or “lumen,” of the gut. It also contains special proteins that help fight against invaders. This mucus and its special compounds are produced by the enterocytes.
We want that mucus layer to be nice and thick to provide a better barrier between the one-cell layer of enterocytes and protect them from “bad” bacteria that can get in there.
FUN FACT: Animal studies show that mice fed a diet low in fibre had thinner mucus barriers.
The third (innermost) layer inside our gut lining is our friendly resident gut microbes. Our guts contain billions of microbes – sometimes 5 pounds worth. Taken together, they’re sometimes referred to as a “superorganism.” These microbes include bacteria as well as other types of friendly microbes.
This layer of gut microbiota has two major functions to help promote a healthy gut lining:
- They crowd out “bad” bacteria by taking up space and eating the “good” food (i.e. fibre and resistant starch, which we’ll get into in a bit).
- They help to regulate the digestion and absorption of nutrients to nourish the first-layer enterocytes. One of the types of compounds they produce are called “short chain fatty acids” (SCFAs). These are considered to be anti-inflammatory and are also used as fuel for the enterocytes.
When the three layers aren’t working optimally, the tight junctions loosen, and leaks occur. This allows unwanted things to enter into the body’s circulation which is one way gut health affects our overall health.
Leaky gut and our gut microbes
Our friendly gut microbes, the third innermost layer of our gut, include hundreds of types of microbes. Some of the main types of bacteria are Bacteroidetes and Firmicutes (e.g. Lactobacillus). We think problems with our gut microbes might actually begin the whole process of leaking guts.
According to Sturgeon and Fasano, 2016:
“It is now clear there is a symbiotic relationship between the microbiome and the host. As early as 2001, it was described that commensal bacteria have an effect on intestinal permeability.”
Here’s how we think this happens, based on the current research:
- The third innermost layer of the gut lining, the microbiota, get out of balance.
- Inflammatory molecules (including zonulin) are released, and fewer anti-inflammatory ones like SCFAs are available.
- This inflammation disturbs the tight junctions in first layer of enterocytes, hence creating tiny leaks which allows passage of harmful compounds into our bodies.
It starts when the gut microbiota are in dysbiosis (an “imbalance” of “good” and “bad” microbes). This promotes an inflammatory response because some of the “bad” microbes are pushing out the “good” ones that produce the anti-inflammatory short chain fatty acids (SCFAs). SCFAs are anti-inflammatory and are also used as fuel by the enterocytes. Some of these SCFAs promote the production of the mucus layer (the second layer), and even help to improve the tight junctions in the enterocytes in the first layer. They produce the SCFAs when they eat fibre and resistant starch.
FUN FACT: One study looked at children who were at risk of developing type 1 diabetes (which is an autoimmune condition). Researchers found that some who had an increase in one of the “bad” microbes went on to develop autoimmunity months later which led to type 1 diabetes.
Another possibility that researchers are looking at is that some of these “bad” bacteria produce a toxin that mimics zonulin.
Zonulin is a protein naturally released by our enterocytes when they’re exposed to certain things we eat, like “bad” bacteria on our food and gliadin (part of the gluten protein found in wheat and other grains). Blood levels of zonulin tend to be higher in people with autoimmune conditions like celiac disease and type 1 diabetes.
All of this increased inflammation then irritates the gut, which can result in loosening of those tight junctions.
Based on the research so far, this is the way we think we develop leaky guts. But, how does this relate to autoimmunity?
Leaky gut, allergies, and autoimmunity
Allergies and autoimmunity are directly linked to our immune system. They result when our immune system works a bit too hard – when our immune cells become a little too active.
Allergies occur when our immune system is activated to fight things that are not harmful, like certain foods, pollen, or pet dander. The body thinks they’re dangerous invaders that must be fought, and sends out immune cells that cause inflammation to try and eliminate the allergen.
Autoimmunity, on the other hand, is when our immune system is activated to fight our own cells and tissues. The immune system becomes “intolerant to self.” For example, type 1 diabetes (an autoimmune disease) occurs when our immune system fights the insulin-producing cells in our pancreas. After continued inflammation, enough of these cells die and we eventually need to start monitoring our own blood sugar levels and provide our bodies with external insulin. This occurs more often in people who have type 1 diabetes in their families.
Many things can contribute to autoimmunity, and leaky gut may be a bigger factor than we once thought. This is because of the impact of allowing undigested food, bacteria, etc. to enter our bodies and how our immune system tries to fight them. A large part of our immune system is located just on the other side of that one-cell thick layer of enterocytes.
When our bodies detect things in our internal circulation that don’t belong (like undigested food or bacteria) our immune system kicks in. This immune response to things that “leaked” into our bodies can cause the release of even more inflammatory compounds this time inside our bodies and bloodstreams (i.e. on the other side of the first layer of enterocytes). The allergic and inflammatory responses that happen around our guts may affect the gut directly. But, once these are absorbed into the bloodstream, they can affect other parts of the body too.
This is the connection we see between leaky gut, allergies, and autoimmunity. It’s not just the leaky gut, it’s the interactions between what leaks into our bodies and our immune system’s response to them.
Having a healthy gut microbiota plays an important role in how our immune systems mature from when we were infants. Dysbiosis in our gut at an early age can promote changes in our immune response, and increase the risk of allergic and autoimmune diseases.
It seems that gut dysbiosis and “leaky gut” might be part of the chain of reactions that lead our immune cells to start attacking things they really don’t need to.
Leaky gut and mental health
Stress and mental health issues are associated with inflammatory bowel diseases and leaky gut.
Stress hormones and moods can result in reduced levels of mood-boosting neurotransmitters in the brain and increase the risk of developing gut disorders, or flare ups of existing gut disorders. Several studies have found that patients with inflammatory gut conditions experienced worsening symptoms after stressful events. Chronic, or long-term, stress and depression is associated with more gut pain, leaky gut, and other inflammatory gut conditions like Crohn’s and ulcerative colitis. Stress can affect changes in the microbiota and the lining of the gut, and can further increase the gut inflammation. In animals, studies show that being under stress increases their intestinal permeability and inflammation.
We used to think that the brain sent direction down to control all parts of our bodies. We’re learning that a lot of the communication between the gut and the brain starts in the gut and goes up to the brain. Several studies show that in about half of people studied, gut symptoms arose before the mood issues did.
People who have gut disorders have a higher risk of developing anxiety or depression. Sometimes experiencing symptoms like abdominal pain, bloating, and discomfort can affect the quality of life and moods of people who have inflammatory bowel disease.
Some animal models of the inflammatory gut condition colitis promoted behavioral changes that are similar to mood disorders in people. Also, mice given an SCFA called butyrate seemed to experience an antidepressant effect.
These links between the gut and mental health are because of the “microbiota-gut-brain axis.” This axis includes many connections between the two of them, including through our nerves and hormones.
When the areas of the brain associated with stress are activated, this initiates the stress response. The stress response is twofold. First, it includes the release of stress hormones (hypothalamic-pituitary-adrenal axis – HPA axis) that go through the whole body. Second, it includes activation of the “fight or flight” (autonomic) part of the body’s nervous system. Both the hormones and autonomic nervous system affect the gut. And these can affect all three layers of the gut lining.
One of the key stress hormones of this HPA-axis is from the adrenal glands (the “A” in HPA). It’s the infamous stress hormone called cortisol. Cortisol is released into the bloodstream when we’re under stress. Cortisol directly affects the gut by reducing our ability to properly digest food, and instead prioritizes survival. It essentially prepares for “fight or flight” by slowing down the “rest and digest” functions.
FUN FACT: Mouse studies show that SCFAs may help to normalize the leakiness in not just our gut lining, but our “brain lining” (e.g. “blood-brain barrier”) too.
What you can do about leaky gut
When our “good” gut microbes are happy eating their favorite foods they have positive effects on our gut – crowding out the “bad” microbes and producing beneficial anti-inflammatory compounds like SCFAs.
FUN FACT: The type of microbes that live in your gut is established by the time you’re 3-5 years old. About 30-40% of it can be influenced by factors such as diet.
According to Aguayo-Patron, 2017:
“Diet is the main factor that influences gut microbiota composition.”
1 – Eat more fresh, unprocessed and minimally processed foods
We’re talking things like:
- Fruits and vegetables
- Nuts and seeds
This is sometimes referred to as an “old fashioned” diet. It includes fresh and minimally processed foods that are closer to the way they’re found in nature. These promote a healthy mix of the “good” gut microbes.
One of the reasons is because these foods contain higher amounts of fiber and “resistant” starch. Sugars and easily-digested starches are broken down and absorbed into the bloodstream as sugar. Resistant starches and fiber, on the other hand, are “resistant” to this process and make it all the way through our intestines to where most of our gut microbes live. These can then become food for our “good” gut microbes and promote their health.
Another way un-processed and minimally processed foods help our gut microbes is because of the lower amounts of trans and saturated fats, and higher amounts of healthy fats like unsaturated and omega-3 fats. Some studies show that diets high in fat tend to promote more “bad” microbes in our guts.
Another possible reason why fresh and unprocessed foods are beneficial is that some of the additives used in ultra-processed foods can also affect our gut microbiota. This leads us to the second thing you can do about leaky gut.
2 – Ditch the ultra-processed and fast foods!
These are the quick and easy foods that are:
- Ready to eat
- Ready to heat
They tend to be high in calories, fat, sugar, salt, and contain artificial additives. These are the foods that have a lot of refined sugar and easily digested starches that raise our blood sugar, and not a lot of fiber and resistant starches. They have more total fat, including trans and saturated fats. Also known as the sad, (standard american diet) it tends to be not very filling and promote obesity.
These types of foods also promote inflammation and gut dysbiosis – factors associated with leaky guts!
People who tend to eat less of these, and more fresh and unprocessed foods tend to have happier gut microbiota, less inflammation, and a nice strong non-leaky gut lining.
3 – Pay attention to potential food intolerances
Some gut symptoms may be related to food intolerances. Certain people may have undiagnosed celiac disease, or be sensitive to gluten and can benefit from removing it from the diet. There are a lot of gluten-free foods available now, however ultra-processed gluten-free foods are still ultra-processed and should be avoided in favor for fresh and unprocessed foods.
Also, some people are intolerant to certain carbohydrates called FODMAPS (fermentable oligo-, di-, and mono-saccharides and polyols). These are found in stone fruits, legumes, lactose-containing foods, and artificial sweeteners.
Ask your health professional to see if you should be tested for food intolerances.
4 – Reduce alcohol
Alcohol can stress our friendly gut microbes and can disrupt the function of our three-layered gut lining. It can cause bacterial overgrowth, and at the same time reduce some of the friendly “good” microbes like Lactobacillus.
FUN FACT: Some “bad” bacteria, including E. coli can produce alcohol, so this may be one of the ways that they contribute to leaky gut.
5 – Consider probiotics
Probiotics are live microorganisms that have a beneficial effect on human health. They are found in fermented foods like yogurt, kefir, kombucha, miso, kimchi, and fermented vegetables. They are also available as dietary supplements.
Infections and use of antibiotics, especially during the first months of life, can have a negative effect on our gut microbiota. If you have to take an antibiotic, ask your healthcare professional if you should also take certain probiotics to help reduce the impact on your gut microbiota.
Clinical trials are supporting the use of probiotics to benefit some inflammatory and other gut conditions.
CAUTION: Before taking any supplements, make sure to read the label and heed the warnings. If you are taking other supplements or medications or if you have a medical condition, be sure to consult with a knowledgeable healthcare professional first.
Leaky gut, or “intestinal permeability” is linked with many conditions of the gut, the body, and the mind. While research is still figuring out exactly how this happens, there are definitely steps you can take today to help optimize your health.
Eat more whole, unprocessed foods, and ditch ultra-processed foods. Reduce alcohol consumption and consider probiotics. And, if you think you may have a food intolerance, be sure to speak with your healthcare professional. For more information go to www.gutrecharge.com
Aguayo-Patrón, S. V., & Calderón de la Barca, A. M. (2017). Old Fashioned vs. Ultra-Processed-Based Current Diets: Possible Implication in the Increased Susceptibility to Type 1 Diabetes and Celiac Disease in Childhood. Foods, 6(11), 100. http://doi.org/10.3390/foods6110100
Brzozowski, B., Mazur-Bialy, A., Pajdo, R., Kwiecien, S., Bilski, J., Zwolinska-Wcislo, M., … Brzozowski, T. (2016). Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis. Current Neuropharmacology, 14(8), 892–900. http://doi.org/10.2174/1570159X14666160404124127
Fasano A. (2011). Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 91(1):151-75. doi: 10.1152/physrev.00003.2008.
Holtmann G, Shah A, Morrison M. (2017). Pathophysiology of Functional Gastrointestinal Disorders: A Holistic Overview. Dig Dis, 35 Suppl 1:5-13. doi: 10.1159/000485409.
Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jačan, A., & Reichmann, F. (2017). Visceral Inflammation and Immune Activation Stress the Brain. Frontiers in Immunology, 8, 1613. http://doi.org/10.3389/fimmu.2017.01613
Kelly, J. R., Kennedy, P. J., Cryan, J. F., Dinan, T. G., Clarke, G., & Hyland, N. P. (2015). Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in Cellular Neuroscience, 9, 392. http://doi.org/10.3389/fncel.2015.00392
Lamprecht, M., Bogner, S., Schippinger, G., Steinbauer, K., Fankhauser, F., Hallstroem, S., … Greilberger, J. F. (2012). Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. Journal of the International Society of Sports Nutrition, 9, 45. http://doi.org/10.1186/1550-2783-9-45
Lerner, A & Matthias, T. (2015). Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev, 14(6):479-89. doi: 10.1016/j.autrev.2015.01.009.
Lerner, A., Neidhöfer, S., & Matthias, T. (2017). The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists. Microorganisms, 5(4), 66. http://doi.org/10.3390/microorganisms5040066
Mu, Q., Kirby, J., Reilly, C. M., & Luo, X. M. (2017). Leaky Gut As a Danger Signal for Autoimmune Diseases. Frontiers in Immunology, 8, 598. http://doi.org/10.3389/fimmu.2017.00598
Slyepchenko, A., Maes, M., Jacka, F.N., Köhler, C.A., Barichello, T., McIntyre, R.S., Berk, M., Grande, I., Foster, J.A., Vieta, E. & Carvalho, A.F. (2017). Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities. Psychother Psychosom, 86(1):31-46.
Sturgeon, C., & Fasano, A. (2016). Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers, 4(4), e1251384. http://doi.org/10.1080/21688370.2016.1251384
Wikipedia. Bacteroidetes. Accessed May 22, 2018.
Wikipedia. Firmicutes. Accessed May 22, 2018.
Wilms, E., Gerritsen, J., Smidt, H., Besseling-van der Vaart, I., Rijkers, G. T., Garcia Fuentes, A. R., … Troost, F. J. (2016). Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial. PLoS ONE, 11(12), e0167775. http://doi.org/10.1371/journal.pone.0167775
World Health Organization, Food and Agriculture Organization. Probiotics. Accessed May 22, 2018.
Xiao, L., van’t Land, B., van de Worp, W. R. P. H., Stahl, B., Folkerts, G., & Garssen, J. (2017). Early-Life Nutritional Factors and Mucosal Immunity in the Development of Autoimmune Diabetes. Frontiers in Immunology, 8, 1219. http://doi.org/10.3389/fimmu.2017.01219