The trouble with leaky gut and what to do about it?

The difference between the healthy and the leaky gut.
People who have an autoimmune disease must have heard or were asked at least once about leaky gut. Science tries to decipher what leaky gut is, what causes it, what problems it causes in turn and how to fix it.
What are your experiences with leaky gut? Participate in our science survey and uncover the patterns of Hashimoto’s.

What is leaky gut?

Our entire digestive system is protected by a thin layer of cells: the intestinal wall. The intestinal wall is the first-line barrier against the food and bacteria in our gut. It keeps the contents of our gut and our abdominal cavity separate [1]. This helps to maintain the balance between oral tolerance to food we eat and an immune reaction to the food, also called food sensitivity.

Leaky gut happens after a damage to the intestinal wall. This damage changes the wall thickness, or creates gaps between the cells in the wall. Leaky gut leads to losing oral tolerance and the onset of food sensitivities.

Mutations in our genes predispose us to develop leaky gut. Environmental factors can trigger the damage. Daily consumption of an industrialized-world diet is the biggest trigger of leaky gut.

Our diet has changed a lot in the past hundred years. It has changed especially in urban areas, where there are no fields to harvest, or wild meat to catch. The food is not eaten only in the harvest season. Crop fields became bigger, and the development of chemical pesticides and insecticides followed. To scale up the production of meat and milk, animals are fed with hormones and antibiotics. Most of these end up in human food too.

In order for food to be eaten out of season, or in the areas where it does not naturally grow, a lot of artificial preservatives were added. To make the food more appealing and tasty, artificial colorings, sweeteners, salt, emulsifiers, organic solvents, gluten, and microbial transglutaminase were added [2]. And finally, in order to lower the transportation costs, food containers were made from lighter materials, such as plastic, which turned out to contain bisphenol A (BPA).

Eating this new style industrial food changed the landscape of our gut. For the most of our Homo Sapiens history we have been eating a low fat, plant-rich diet, and then we changed to high fat, high sugar diet. Scientists have shown that the bacterial composition (aka the microbiome) changes tremendously fast when switching diets. In mice it happened within one day [3].

Our digestive system contains a lot of bacteria. To be precise our gut contains 10 trillion bacterial cells. We have more bacterial cells in our body than we have our own cells [4–6]. These bacteria are the most crucial part of our nutrition, metabolism, development and proper functioning of the immune system [6,7].

Why are there so many bacteria in our gut? Because our gut is huge. It is so neatly packed, because if we would spread it out, our gut would cover close to 200 square meters of surface. So, in this vast surface our immune system comes in very close contact with the foods we eat and with all of the bacteria [8].

Big gut, lots of bacteria; how do we control it? Through diet. Diet is the factor determining which bacteria will have a better environment and more food resources to grow. And in the next step, the composition of our microbiome (different types of bacteria) will determine the balance of our immune system. Certain bacteria types might be the ones driving the damage to the intestinal wall. And by having a specific bacteria in our gut, our immune cells develop in a specific way too, highly dependent on the bacterial type. There are a lot of immune cells and they render the host more susceptible to chronic autoimmune inflammation [6,9,10].

So how do bacteria work their way through to the abdominal cavity? The intestinal wall is composed of a thin layer of cells that are covered with mucus molecules. That mucus layer is thick, and it protects the cells of the intestinal wall from coming in direct contact with bacteria. But at the same time this layer is very effective at absorbing nutrients into the bloodstream.If a person has an autoimmune disease, this mucus layer is compromised; it becomes thinner, and more bacteria get to go directly to the intestinal wall and have free access to the bloodstream.

At the onset of an autoimmune condition, when the intestinal wall is covered with a sufficient layer of mucus, food passage through our gut slows down. By slowing down, it allows more time for bacteria and food particles to reach to intestinal wall and go through it. So, the disease usually starts slow, and then it builds up.

What triggers leaky gut?

Several things trigger leaky gut: certain foods, synthetic chemicals (e.g. medications or preservatives and pesticides), infections and stress.

A big problem with food is the way it is prepared: high temperatures are used in industrial food conservation. This conservation process creates certain chemicals as a byproduct, and they have been shown to cause inflammation and further exacerbate leaky gut [11–13].

Medications such as Aspirin, Motrin, Advil, antibiotics, NSAIDs and antacids contribute to the damage to the gut, by making the mucosal layer very thin. Stress, smoking, alcohol consumption and infections are factors of exacerbation of immune system and inducing the leaky gut too [14,15].

Once the immune system is triggered, the vicious circle of leaky gut — inducing inflammation, inducing production of more immune cells around the intestinal wall, making the wall more porous — continues [16].

In its essence, leaky gut is a consequence of our genes and our environment: genes make us more likely or more sensitive to acquire the condition, and the environment serves as a trigger, or a last step in the onset of the disease [17].

How does stress do it? Our gut has a network of neurons which is well connected with our brain. The neuronal system found in our gut (aka the enteric nervous system) is sometimes called the second brain. This second brain is heavily under the influence of the gut bacteria and can make the gut more leaky too [18–20].

So far, leaky gut has been most studied in celiac autoimmune disease, and it was shown that daily consumption of wheat product triggers autoimmune disease through increasing the leaky gut [21].

Problems with leaky gut are detected in other autoimmune diseases, such as rheumatoid arthritis (RA), cystic fibrosis, multiple sclerosis, irritable bowel syndrome (IBS), diabetes type 1 and 2 [22].

What to do about the leaky gut?

Treatments for leaky gut are not well studied, and a lot more experimental results are needed to understand what treatments can help us and how.

Facts that are known so far:

Antibiotics can sometimes help to reduce the overgrowth of bad bacteria and through that balance out the immune system in both rheumatoid arthritis and IBS. Unfortunately, this seems to be mostly a temporary fix [23,24].

Therapy using medicines that block tumor necrosis factor alpha (TNFα) reduce inflammation of mucosa and reduce leaky gut.

Zinc, butyrate and some probiotics might help improve the mucosal layer and tighten the intestinal wall [8].

Glutamine, an essential amino acid, a natural compound curcumin (turmeric) as well as prebiotics and probiotics can block the inflammation, and reduce leaky gut (reviewed in [25]).

While some research claims leaky gut can be reversed, other research shows it is not possible or likely [26]. More research with an individual approach should be done to understand why it works for some people, while it does not for the others.

What are your experiences with leaky gut? You can tell us at hello@boosthealthapp.com or participate in our science survey.

References:

1. Farhadi A et al. Intestinal barrier: an interface between health and disease (2003).

2. Lerner A et al. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease (2015).

3. Turnbaugh PJ et al. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice (2009).

4. Savage DC. Microbial ecology of the gastrointestinal tract (1977).

5. Orel R et al. Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease (2014).

6. Brown K et al. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease (2012).

7. Borody TJ et al. Fecal microbiota transplantation: indications, methods, evidence, and future directions (2013).

8. Michielan A et al. Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut (2015).

9. Mangan PR et al. Transforming growth factor-beta induces development of the T(H)17 lineage (2006)

10. Zhang YJ et al. Impacts of gut bacteria on human health and diseases (2015).

11. Uribarri J et al. Diet-derived advanced glycation end products are major contributors to the body’s AGE pool and induce inflammation in healthy subjects (2005).

12. Bengmark S. Advanced glycation and lipoxidation end products — amplifiers of inflammation: the role of food (2007).

13. Webster J et al. Maillard reaction products in food as pro-inflammatory and pro-arteriosclerotic factors of degenerative diseases (2005).

14. Bailey MT et al. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation (2011).

15. Davies TF. Infection and autoimmune thyroid disease (2008).

16. Fasano A. Leaky gut and autoimmune diseases (2012).

17. Vojdani A. For the assessment of intestinal permeability, size matters (2013).

18. Bienenstock J et al. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms (2010).

19. Collins SM et al. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease (2009).

20. Gershon MD. The enteric nervous system: a second brain (1999).

21. de Punder K et al. The dietary intake of wheat and other cereal grains and their role in inflammation (2013).

22. de Kort S et al. Leaky gut and diabetes mellitus: what is the link? (2011).

23. Hill DA et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis (2010).

24. Khan KJ et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis (2011).

25. Rapin JR et al. Possible links between intestinal permeability and food processing: A potential therapeutic niche for glutamine (2010).

26. Ventura MT et al. Intestinal permeability in patients with adverse reactions to food (2006).