Leaky gut and inflammation

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The lining of our digestive tract, also called our gut wall, is semi-permeable by nature. It is made up of a single cell layer with tight gaps or ‘junctions’ between the cells. These tight junctions allow only properly digested fats, proteins, starches, water and micronutrients to pass through so they can be taken up into the bloodstream and nourish our body. In a healthy intestinal tract, the intestinal tight junctions limit the transport of large molecules (>500 Da) across the intestinal wall.

The gut wall also functions as a barrier to keep out bacteria and other harmful foreign substances which may enter the digestive tract, as well as undigested food particles.

In an unhealthy intestine the tight junctions become ‘leaky’ and these large molecules, which can include unprocessed proteins or large amino acids that have intact antigenic sites on them, can then get into the bloodstream. Several factors, for example undiagnosed food intolerances, infections and stress, can cause the tight junction of the gut lining to become ‘leaky’ — a condition known as ‘leaky gut’ or ‘intestinal permeability’.

A leaky gut allows substances such as bacteria, toxins, fungi, parasites and undigested food particles to enter the bloodstream. Scott, T. and Axe, J. (June 2016). Anxiety: The Stressed and Toxic Gut. [online] The Anxiety Summit, Season 4. Available at: http://season4.theanxietysummit.com/ [accessed 6 Dec. 2017]. Once such substances have entered the bloodstream they can cause an inflammatory reaction or an autoimmune response.

  • When foreign substances pass into the blood-stream, they activate antibodies and alarm cytokines
  • Cytokines alert lymphocytes (white blood cells) to battle the particles
  • Oxidants are produced, causing irritation and inflammation within and outside of the digestive system

Leaky gut is commonly seen in patients presenting with intestinal inflammation, food allergies and intolerances, and coeliac disease, after radiation or chemotherapy treatment.

Symptoms of leaky gut

Leaky gut is an often overlooked problem as it has few or no symptoms, or masquerades as seemingly unrelated symptoms. Wright, S. (2016). Is Leaky Gut The Real Reason You’re Sick? [online] Solving Leaky Gut. Available at: https://solvingleakygut.com/is-your-body-suffering/ [accessed 27 Dec. 2017]. However, the following symptoms can be indicative of a leaky gut:

  • Abdominal pain
  • Arthritis
  • Autoimmune disease
  • Chronic constipation
  • Diarrhea
  • Difficulty gaining or losing weight
  • Digestive complaints (e.g.: bloating, flatulence, reflux)
  • Food intolerances
  • Headaches
  • Irritable Bowel Syndrome (IBS)
  • Joint pain
  • Muscle pain
  • Seasonal allergies
  • Skin issues (e.g.: eczema, itchy skin, etc.)
  • Thyroid issues

Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 248. Scott, T. and Axe, J. (June 2016). Anxiety: The Stressed and Toxic Gut. [online] The Anxiety Summit, Season 4. Available at: http://season4.theanxietysummit.com/ [accessed 6 Dec. 2017].

  • Brain fog
  • Depression
  • Fatigue
  • Anxiety
    • Research by Premsyl Bercik and Stepen Collins from the McMaster University in Ontario looked into colonizing germ-free mice with the bowel contents of people with irritable bowel syndrome, which induces constipation, diarrhoea, pain and low-grade inflammation without known cause
    • The animals developed leaky intestines, their immune system was activated, and they produced pro-inflammatory metabolites, many with known nervous system effects, and the mice also displayed anxious behaviour
    • This may indicate that changes in the gut flora can lead to increased gut permeability and behavioural changes including anxiety Schmidt, C. (2015). Mental health may depend on creatures in the gut. [online] Scientific American. Available at: https://www.scientificamerican.com/article/mental-health-may-depend-on-creatures-in-the-gut/ [accessed 27 Dec. 2017].
  • Insomnia
    • A leaky gut can affect sleep due to the consequent increase in inflammation and increased levels of cytokine (the inflammatory messengers)
    • Studies have found that those who do not sleep well have higher cytokine levels than healthy sleepers and that elevated cytokines and chronic inflammation can lead to insomnia
    • The pain associated with inflammation such as headaches or stomach pain can lead to a disruption in the sleeping pattern
    • Higher cortisol levels are common in patients with leaky gut, and the increased levels of this stress hormone can make it difficult to fall asleep and also stay asleep Reed, M. (2016). Is leaky gut to blame for your insomnia? [online] Health Central. Available at: https://www.healthcentral.com/article/is-a-leaky-gut-to-blame-for-your-insomnia [accessed 27 Dec. 2017].
  • Poor attention
    • Leaky gut can lead to food allergies and to incompletely digested particles called peptides to cross into the bloodstream, which can trigger hyperactivity and ADHD in some individuals (2016). ADHD – Attention Deficit Hyperactivity Disorder. [online] Smart Nutrition. Available at: http://www.smartnutrition.co.uk/conditions/kids-health/adhd-attention-deficit-hyperactivity-disorder/ [accessed 27 Dec. 2017].

Selhub, E. M., Logan, A. C. and Bested, A. C. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. [online] Journal of Physiological Anthropology, 33:2. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24422720 [accessed 27 Dec. 2017].

Possible causes of leaky gut

Western diets high in refined fats, sugars, processed foods, fried, roasted or broiled foods, carbonated drinks, and low fibre foods do not support a healthy gut lining. Lipski, E. (1996). Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion. 2nd ed. McGraw-Hill Education, pp. 95-108. Minocha, A. (2014). Is It Leaky Gut or Leaky Gut Syndrome? Shreveport, LA: Logos Enterprises LLC.

Regular or excessive consumption of these foods and drinks can cause an overgrowth of harmful bacteria, damage the gut lining and contribute to the formation of leaky gut. Minocha, A. (2014). Is It Leaky Gut or Leaky Gut Syndrome? Shreveport, LA: Logos Enterprises LLC.

If our bodies are incapable of digesting specific foods such as gluten and dairy due to an intolerance to these foods, the cumulative effect of consuming such foods can damage the gut lining and cause leaky gut. Gottfried, S. (2013). The Hormone Cure. New York: Scribner, p. 248.

Adequate fluid intake is essential to maintain gut permeability. Minocha, A. (2014). Is It Leaky Gut or Leaky Gut Syndrome? Shreveport, LA: Logos Enterprises LLC.

Not drinking sufficient fluids throughout the day can cause the bowel contents to harden and linger around the digestive tract for much longer than normal, which in turn can lead to an overgrowth of bacteria and inflammation of the bowel lining, leading eventually to leaky gut.

Candida is a form of yeast which resides in the human gut.

Under normal circumstances it causes no issues. However, when allowed to proliferate due to stress, a diet high in sugar and carbohydrates or the use of antibiotics, it can mutate into a harmful fungal form.

This fungal form is able to push its way into the lining of the intestinal wall and emit toxins, and therefore an overgrowth of Candida can be a contributing factor to the development of leaky gut. Lipski, E. (1996). Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion. 2nd ed. McGraw-Hill Education, pp. 95-108.

Studies show that intestinal inflammation and forms of intestinal permeability have been documented to increase with age. Man, A. L., Bertelli, E., Rentini, S., Regoli, M., Briars, G., Marini, M., Watson, A. J. and Nicoletti, C. (2015). Age-associated modifications of intestinal permeability and innate immunity in human small intestine. [online] Clinical Science, 129 (7), pp.515-27. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25948052 [accessed 27 Dec. 2017].

A causal factor is a natural decline in stomach acid production as we age. By age 50 most women and men produce less than half the stomach acid they did in their twenties. Gluck, M. and Edgson, V. (2010). It Must Be My Hormones. Camberwell, Vic.: Penguin Group (Australia), p. 189.

Stomach acid is essential:

  • For proper digestion and absorption of nutrients
  • To help keep the pH in the digestive system optimal, which is crucial for maintaining a correct balance of beneficial and harmful bacteria and fungi naturally present in our gut
  • Stomach acid has the ability to neutralise harmful bacteria, fungi and other pathogens which may enter our digestive tract through intake of food, water or air

Studies have found that those who do not sleep well have elevated levels of the stress hormone cortisol as well as elevated levels of inflammatory markers in the body. Basta M., Chrousos, G. P., Vela-Bueno, A. and Vgontzas, A. (2007). Chronic Insomnia and Stress System. Sleep Medicine Clinics, 2 (2), pp. 279–291. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2128619/ [accessed 27 Dec. 2017].

Both stress and inflammation can contribute to the formation of leaky gut. Raison, C. L., Rye, D. B., Woolwine, B. J., Vogt, G. J., Bautista, B. M., Spivey, J. R. and Miller, A. H. (2010). Chronic interferon-alpha administration disrupts sleep continuity and depth in patients with hepatitis C: association with fatigue, motor slowing, and increased evening cortisol. [online] Biological Psychiatry, 68 (10), pp. 942-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20537611 [accessed 27 Dec. 2017].

How poor sleep can impact our mental health.

When we are under stress:

  • We produce less of a substance called Secretory Immunoglobulin A (SIgA), an antibody which plays an important role in the immune function of the mucous membranes in our gut
  • Low levels of SIgA leave our gut exposed to infection with bacteria, viruses and parasites which can contribute to the development of leaky gut
  • Stress may also slow down digestion, bowel motility and blood flow to digestive organs and produce toxic metabolites, which can contribute to and worsen leaky gut Lipski, E. (1996). Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion. 2nd ed. McGraw-Hill Education, pp. 95-108. 
  • This can lead to further permeability and also directly and negatively stimulate the brain, making it more susceptible to mood disorders

How stress can impact our mental health.

  • A healthy gut microbiota (with a good balance of healthy bacteria) is essential in maintaining the physical integrity if the gut and ensuring the right gut permeability
  • When however the microbiota is unhealthy, it can lead to leaky gut
  • Blastocystis Hominis, Giardia, Helicobacter, Salmonella, Shigella, Yersinia enterocolitica, amoebas and other parasite can also irritate the gut lining Lipski, E. (1996). Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion. 2nd ed. McGraw-Hill Education, pp. 95-108.

Pregnant women have higher rates of gut leakiness due to the increased stress resulting in increased activation of inflammatory pathways. Selhub, E. M., Logan, A. C. and Bested, A. C. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. [online] Journal of Physiological Anthropology, 33:2. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24422720 [accessed 27 Dec. 2017].

Several pharmaceuticals and supplements can damage the gut lining:

  • NSAIDs, such as ibuprofen and aspirin, damage brush borders and allow microbes, partially digested food particles and toxins, to enter the bloodstream Selhub, E. M., Logan, A. C. and Bested, A. C. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. [online] Journal of Physiological Anthropology, 33:2. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24422720 [accessed 27 Dec. 2017].
  • Antibiotics can destroy the beneficial bacteria. They damage the intestines by fostering the growth of Candida albicans and other pathogenic fungi and yeasts, which in turn can lead to leaky gut Grisanti, R. (2017). Leaky Gut: Can This Be Destroying Your Health? [online] Functional Medicine University. Available at: http://www.functionalmedicineuniversity.com/public/Leaky-Gut.cfm [accessed 27 Dec. 2017].
  • Iron supplements
  • Birth control pills and steroid drugs can create conditions that help to feed fungi, which damage the gut lining
  • Chemotherapy drugs and radiotherapy can have a significant effect on the gastrointestinal balance Lipski, E. (1996). Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion. 2nd ed. McGraw-Hill Education, pp. 95-108.

Leaky gut and gut dysbiosis can be caused by chronic exposure to toxins in the gut.

Pesticides and herbicides such as glyphosate regularly used on non-organic cereal crops, chlorine, etc. have all been found to disrupt healthy levels of gut bacteria and cause inflammation, leading to gut dysbiosis and leaky gut.

How toxicity can impact our mental health.

Zonulin, a protein that regulates gut permeability, can be produced in excess by some people, causing leaky gut. Fasano, A. (2011). Zonulin and its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer”, Physiological Reviews, 91 (1), pp. 151-75. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21248165 [accessed 27 Dec. 2017].

How leaky gut can lead to mental health issues

There is increasing evidence to associate leaky gut with mental health problems.

A recent study published in Neuro Endocrinology Letters showed that leaky gut can cause a number of neurocognitive disorders.

The increase in gut permeability and associated release of pro-inflammatory cytokines and other chemicals can lead to depression, anxiety, poor attention and concentration, poor memory and social problems. Selhub, E. M., Logan, A. C. and Bested, A. C. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. [online] Journal of Physiological Anthropology, 33:2. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24422720 [accessed 27 Dec. 2017].

Leaky gut can have a negative impact on mental health in the following ways:

The blood brain barrier is a semi permeable membrane which protects our brain from harmful substances entering, while allowing the passage of brain nutrients such as water, amino acids and glucose. A leaky gut can also contribute to a leaky blood brain barrier.

  • The membranes of a large variety of bacteria contain molecules called lipopolysaccharides (LPS)
  • A leaky gut can allow LPS to enter the bloodstream
  • LPS are endotoxins and can trigger inflammation in the body, contributing to a gradual deterioration of the blood-brain barrier
  • A leaky blood-brain barrier may allow harmful substances to enter the brain cavity and contribute to neuro-inflammation and disturbed brain function
  • High levels of LPS in the bloodstream have in fact been linked to the development of Parkinson’s, Alzheimer’s, depression, autism, learning difficulties and cognitive decline Guthrie, C. (2013). Autoimmune Disorders: When Your Body Turns On You. [online] Experience Life. Available at: https://experiencelife.com/article/autoimmune-disorders-when-your-body-turns-on-you/ [accessed 27 Dec. 2017].

 

The nutrients contained within the foods we eat are necessary for the production of hormones and neurotransmitters. Leaky gut can prevent proper digestion of food and malabsorption of essential nutrients, which can lead to nutritional deficiencies and contributes to an imbalance in hormone and neurotransmitter production.

Imbalanced hormone and neurotransmitter levels can lead to a variety of mental health symptoms such as depression, insomnia and anxiety.

When large food molecules manage to pass the leaky gut walls, the immune system will label them as “invaders” and launch an immune attack on them. The resulting over-activation of the immune system can cause systemic inflammation, and can sometimes trigger an autoimmune reaction. “Auto” means self, and autoimmune means your immune system takes aim at itself. Autoimmune disorders can be triggered by a genetic predisposition, an environmental trigger, and a leaky gut.

The correlation between autoimmune disease and mental health issues is demonstrated by the fact that

  • Being hospitalized for an autoimmune disease has been shown to increase the risk of being hospitalized for a mood disorder by 45%
  • Being hospitalised for an infection increased the risk of being diagnosed with mood disorder by 62% Benros, M. E., Waltoft, B. L., Nordentoft, M., Ostergaard, S. D., Eaton, W. W., Krogh, J. and Mortensen, P. B. (2013). Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. [online] JAMA Psychiatry, 70 (8), pp. 812-20. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23760347 [accessed 27 Dec. 2017].
  • Drugs to treat autoimmune diseases, such as steroids can also affect the balance of gut bacteria and increase intestinal permeability
  • When leaky gut and intestinal inflammation are present, toxic particles move into the bloodstream where they can trigger microglial inflammation in the brain Guthrie, C. (2013). Autoimmune Disorders: When Your Body Turns On You. [online] Experience Life. Available at: https://experiencelife.com/article/autoimmune-disorders-when-your-body-turns-on-you/ [accessed 27 Dec. 2017].
  • This inflammation can result in brain degeneration and changes in mood
  • Perivascular areas of the brain, such as the hypothalamus and limbic system, are especially vulnerable to inflammation and contribute to “sickness behavior” such as anhedonia (lack of joy, fatigue, etc.)

LPS (lipopolysaccharide)

One of the most damaging substances for the brain from the gut is Lipopolysaccharides or LPS:

  • The presence of LPS in the gut is unavoidable as it is an important component in the protective outer membrane of certain types of bacteria called gram-negative bacteria
    • LPS is released systemically from bacteria in response to cell division, death and particularly antibiotic treatment against bacterial infection Perlmutter, D. and Loberg, K. (2015). Brain Maker. London: Yellow Kite.
    • LPS also protects these bacteria from being digested by bile salts from the gall bladder
    • Under normal circumstances, LPS is not allowed into the bloodstream, but when the tight junctions of the gut are compromised leading to leaky gut, LPS can enter the bloodstream Guthrie, C. (2013). Autoimmune Disorders: When Your Body Turns On You. [online] Experience Life. Available at: https://experiencelife.com/article/autoimmune-disorders-when-your-body-turns-on-you/ [accessed 27 Dec. 2017].
  • Once in the bloodstream it can cause inflammation throughout the body, and is considered an endotoxin (a toxin from within the body)
    • LPS exerts its effects by acting on cells of the innate immune system, particularly macrophages and monocytes with resulting activation of the immune response
  • LPS levels in the blood are indicative not only of inflammation but also of leakiness of the gut

LPS, allowed into the bloodstream by leaky gut, can alter brain chemistry, cause inflammation and neuro-inflammation, and higher levels have been found in conditions such as Parkinson’s, Alzheimer’s, depression, autism, learning difficulties and cognitive decline.

  • Injecting LPS into animals was found to correlate with substantial learning deficits Perlmutter, D. and Loberg, K. (2015). Brain Maker. London: Yellow Kite.
  • These deficits were accompanied by an increase in beta-amyloid in the hippocampus, the key memory centre of the brain
  • Elevated levels of beta-amyloid are present in Alzheimer’s disease
  • Alzheimer’s patients have 3x the levels of LPS as in healthy controls Perlmutter, D. and Loberg, K. (2015). Brain Maker. London: Yellow Kite.
  • Experiments examining the connection between LPS and intestinal permeability have found direct correlations between LPS levels and Parkinson’s disease Guthrie, C. (2013). Autoimmune Disorders: When Your Body Turns On You. [online] Experience Life. Available at: https://experiencelife.com/article/autoimmune-disorders-when-your-body-turns-on-you/ [accessed 27 Dec. 2017].
  • Patients with Parkinson’s disease show much higher levels of LPS than healthy controls Forsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B. and Keshavarzian, A. (2011). Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. [online] PLoS One, 6 (12). Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028032 [accessed 27 Dec. 2017].
  • LPS has been shown to decrease the availability of tryptophan and zinc, both of which are important for the production of the key neurotransmitters for mental health — serotonin and GABA respectively
  • LPS has been shown to play a role in depression, as small elevations in LPS are known to provoke depressive symptoms Selhub, E. M., Logan, A. C. and Bested, A. C. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. [online] Journal of Physiological Anthropology, 33:2. Available at: https://www.ncbi.nlm.nih.gov/pubmed/24422720 [accessed 27 Dec. 2017].

How inflammation can impact our mental health.

IBD and leaky gut are two closely related disorders. IBD severely impacts the integrity of the gut lining leading to leaky gut, and those who have developed leaky gut are more susceptible to developing IBD. Michielan, A. and D’Inca, R. (2015). Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut. [online] Mediators of Inflammation. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637104/ [accessed 28 Dec. 2017].

Inflammation in the gut can manifest as Inflammatory Bowel Disease (IBD) such as Ulcerative Colitis and Crohn’s disease.

Statistics show that these conditions are correlated with higher rates of mood disorders such as depression and anxiety  Greenblatt, J. (2011). The Breakthrough Depression Solution. North Branch, MN: Sunrise River Press, p. 118.

Stress may promote the development and exacerbation of IBD and anxiety is common in the development and persistence of IBD.

Possible causes of IBD

  • Heightened sensitivity to stress leading to an exaggerated stress response
  • Bacterial, viral or parasitical infection
  • Food sensitivities, intolerances or allergies
  • Leaky gut

The most common food contributors in IBD are:

    • Barley
    • Chocolate
    • Citrus fruits
    • Coffee
    • Corn
    • Dairy
    • Eggs
    • Nuts
    • Oats
    • Onions
    • Peanuts
    • Potatoes
    • Rye
    • Shellfish
    • Soya
    • Tea
    • Wheat