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Leaky Gut

 

The concept of “leaky gut” is emerging as a potentially significant factor in a number of diseases and health conditions. Simply defined, a leaky gut is manifest when the intestine wall exhibits excessive permeability, allowing foreign proteins and other substances to be absorbed into the blood stream. This process is proposed to trigger inflammatory and immune system reactions that in turn can contribute to a number of health conditions and illnesses including obesity, chronic fatigue syndrome, fibromyalgia, rheumatoid arthritis, lupus, migraines, multiple sclerosis, and autism.

 

Research does not yet support the existence of a specific, singular entity or “leaky gut syndrome” nor a direct cause and effect with any specific illness, but there is growing evidence that impaired permeability of the intestine is a significant player in many disease processes. In addition, there appears to be a relationship between leaky gut and an impaired blood brain barrier, creating a similar phenomenon in which foreign substances may enter the brain and central nervous system, thereby contributing to chronic pain and psychiatric illness.

 

It is believed there may be a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus, the concept of a microbiome-brain-gut axis is emerging and is the subject of exciting new research.

 

See Also:

Visceral Pain Syndromes

Irritable Bowel Syndrome (IBS)

L-Glutamine

 

 

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Leaky Gut

The human body interfaces with the external environment at multiple sites, including mucosal surfaces of the airways, oral cavity, digestive tract and genitourinary tract, and the skin. Although the skin is the most visible site of interface, the combined area of the mucosal surfaces is much greater than that of the skin. Mucosal surfaces are also the primary sites at which the immune system’s mucosa-associated lymphoid tissue (MALT) is exposed to  the external environment which is greatest in the gastrointestinal (GI) tract, the largest mucosal surface. The GI tract is in continuous contact with dietary antigens (substances that can potentially trigger an immune response) and diverse microorganisms. Thus, mucosal surfaces, particularly in the intestines, are crucial sites of immune regulation.

 

Epithelial cells are the cells that that covers the mucosa and establish and maintain the barrier to the external environment, including the contents of the intestine. There are specialized junctional complexes called “tight junctions” that provide the intestinal epithelial barrier function.

 

The normal, healthy barrier is selectively permeable to allow fluids and nutrients to be absorbed while preventing other foreign substances and toxins from penetrating. When this intestinal barrier is compromised due to breakdowns between the tight junctions between one epithelial cell and another or through other mechanisms, it is termed a “leaky gut.” Loss of tight junction integrity and increased intestinal permeability to macromolecules are associated with the development of Inflammatory bowel diseases (I.e. Crohn and Ulcerative Colitis), Irritable Bowel Syndrome (IBS) and celiac disease.


Proposed Causes or Contributing Factors of Leaky Gut

  1. Alcohol use
  2. Antibiotic use
  3. Celiac disease
  4. Crohn’s disease
  5. Exposure to environmental toxins
  6. Glutens
  7. Immunosuppression
  8. Injury/trauma
  9. Intestinal infections (Giardia lamblia, salmonella, malaria, Ascaris lumbricoides, hepatitis A, Rotavirus, and non-specific gastroenteritis)
  10. Low-fiber diet
  11. Milk Casein
  12. NSAIDs
  13. Severe infection/sepsis
  14. Stress


The Consequences of a Leaky Gut

It is believed that the consequences of a leaky gut include the initiation and/or maintenance of a growing number of disease processes, including various GI conditions such as Irritable Bowel Syndrome (IBS), Celiac Disease and inflammatory bowel diseases including Crohn’s Disease and Ulcerative Colitis. However, a leaky gut may also  impact other conditions, especially those that are stress-related including most psychiatric disorders, including anxiety and depression, as well as  fibromyalgia, chronic regional pain syndrome, migraine headaches and others.

 

Diagnosis of Leaky Gut

Certain compounds can be given to people orally to test the function of the intestinal barrier. These “permeability markers” passively cross the intestinal epithelial layer and are not metabolized. Some examples are lactulose, cellobiose, mannitol and polyethylene glycols. However, while many disease states, especially Crohn’s and celiac disease, are associated with an increase in intestinal permeability, the indications for testing for altered permeability are not well established.

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In specific clinical circumstances, the diagnosis of altered intestinal permeability can be helpful. There are well-documented intestinal permeability changes in active celiac disease. Permeability tests can be used to assess the successful avoidance of gluten, to confirm the diagnosis, or to determine the effect of treatment. In addition, increased sugar permeability in the intestine may be the result of severe inflammation and can be used to assess exacerbations of Crohn’s disease..

 

Management of Leaky Gut

There is some uncertainty regarding the indication to treat increased intestinal permeability given that the cause-effect relationship with most disease states is unknown. However, in specific circumstances it may be justified.

There are some interventions supported by the medical literature that may repair or prevent further damage to the intestinal wall and normalize a leaky gut.  One important recommendation is to avoid use of NSAIDs and alcohol, which are both known to increase intestinal permeability. If the theoretical mechanisms are correct, these substances could start a cycle of increased permeability, inflammation, and immune system response leading to yet further altered permeability.

 

Diet and Leaky Gut

Both preclinical and clinical studies show that dietary components can affect intestinal permeability. In particular, high fat diets are associated with a greater intestinal permeability while meals rich in fiber and fruit have been demonstrated to reduce high fat/high carbohydrate meal-induced increases in intestinal permeability and the inflammatory response. High fat diets can also influence the gut microbiota and have been demonstrated to increase the Firmicutes: Bacteriodetes ratio and induce the growth of Enterobacteriaceae – both conditions associated with dysbiosis, or unhealthy balances of the microbiota of the intestine.

 

Prebiotics and Probiotics

A probiotic is defined as “a live bacteria which when administered in adequate amounts confers a health benefit on the host” (WHO, 2001). Although probiotic health claims have been exaggerated, it is evident that certain strains may demonstrate beneficial effects on the intestinal barrier. Probiotics have been promoted as beneficial in the management of various psychiatric conditions, especially depression. The term “psychobiotics” has been recently proposed to encompass the sub-types of probiotics that may be capable of modulating the brain-gut-microbiota axis to have a beneficial eðect on mood, anxiety and cognition. However, despite a theoretical role of probiotics in depression, there is no definitive proof for the clinical benefit of probiotics for depression.

 

A prebiotic effect is defined as “the selective stimulation of growth and/or activity(ies) of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host.” Preclinical and clinical studies have demonstrated that certain prebiotics alter the gut microbiota, can reduce low grade inflammation and improve metabolic function. Animal studies suggests that prebiotic galacto-oligosaccharides (GOS) can improve intestinal barrier function improve intestinal permeability and tight junction integrity.  Prebiotics have also been shown to influence brain neurochemistry and behavior.

 

L-Glutamine

While amino acid L-Glutamine has many physiologic functions in the kidney, liver, muscle, gut and other organs, the gut mucosa is the major site of glutamine metabolism. L-Glutamine plays a vital role in the maintenance of mucosal integrity. Glutamine, once considered a nonessential amino acid, is now considered a “conditionally essential” amino acid. In the guta, glutamine is the most important nutrient providing fuel for metabolism, regulating cell proliferation, repair and maintaining the gut barrier functions.

 

In times of stress, trauma, heavy exercise, sepsis and post surgery, thc gut’s need for glutamine is exceeded by the gut’s ability to manufacture glutamine, creating a deficient state that can lead to leaky gut. There is good evidence to indicate that L-glutamine is the essential dietary supplement to help maintain mucosal integrity and barrier function under physiologic and pathophysiologic conditions. L-Glutamine has also been shown to be beneficial in decreasing intestinal permeability induced by NSAIDs (non-steroidal anti-inflammatory drugs), critical illness and post-surgery.


Whole food, digestible sources of glutamine include meat, fish, eggs, beans, milk and cheese, breast milk, bone broth, raw spinach, raw parsley, kombu and cabbage. L-Glutamine supplements are readily available and affordable.

See: L-Glutamine

 

 

References:

 

Leaky Gut – Overviews

  1. intestinal-mucosal-barrier-function-in-health-and-disease-2009
  2. a-brief-evidence-based-review-of-two-gastrointestinal-illnesses-irritable-bowel-and-leaky-gut-syndromes-2004
  3. breaking-down-the-barriers-the-gut-microbiome-intestinal-permeability-and-stress-related-psychiatric-disorders-2015


Leaky Gut – Glutamine

  1. possible-links-between-intestinal-permeablity-and-food-processing-a-potential-therapeutic-niche-for-glutamine-2010
  2. glutamine-supplementation-decreases-intestinal-permeability-and-preserves-gut-mucosa-integrity-in-an-experimental-mouse-model-pubmed-ncbi
  3. role-of-glutamine-in-protection-of-intestinal-epithelial-tight-junctions-2012
  4. effect-of-glutamine-on-the-intestinal-permeability-changes-induced-by-indomethacin-in-humans-1999

 

Leaky Gut – Microbiome Overviews

  1. diet-rapidly-and-reproducibly-alters-the-human-gut-microbiome-2014
  2. metabolome-of-human-gut-microbiome-is-predictive-of-host-dysbiosis-2015
  3. gut-microbiota-as-a-key-player-in-triggering-obesity-systemic-inflammation-and-insulin-resistance
  4. obesity-driven-gut-microbiota-inflammatory-pathways-to-metabolic-syndrome-2015
  5. gut-brain-axis-the-role-of-gut-microbiota-in-psychiatric-disorders-2015
  6. the-psychomicrobiotic-targeting-microbiota-in-major-psychiatric-disorders-a-systematic-review-2014
  7. non-alcoholic-fatty-liver-disease-diet-and-gut-microbiota-2014
  8. the-gut-microbiota-of-nonalcoholic-fatty-liver-disease-current-methods-and-their-interpretation-2015
  9. probiotics-and-prebiotics-present-status-and-future-perspectives-on-metabolic-disorders-2016

 

Leaky Gut, Microbiome – Diet

  1. diet-rapidly-and-reproducibly-alters-the-human-gut-microbiome-2014

 

Leaky Gut, Microbiome – Obesity

  1. gut-microbiota-as-a-key-player-in-triggering-obesity-systemic-inflammation-and-insulin-resistance
  2. obesity-driven-gut-microbiota-inflammatory-pathways-to-metabolic-syndrome-2015

 

Leaky Gut, Microbiome – Psychiatric Disorders

  1. gut-brain-axis-the-role-of-gut-microbiota-in-psychiatric-disorders-2015
  2. the-psychomicrobiotic-targeting-microbiota-in-major-psychiatric-disorders-a-systematic-review-2014

 

Leaky Gut, Microbiome – Non-Alcoholic Fatty Liver Disease

  1. non-alcoholic-fatty-liver-disease-diet-and-gut-microbiota-2014
  2. the-gut-microbiota-of-nonalcoholic-fatty-liver-disease-current-methods-and-their-interpretation-2015

 

Leaky Gut, Microbiome – Prebiotics & Probiotics

  1. probiotics-and-prebiotics-present-status-and-future-perspectives-on-metabolic-disorders-2016

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Emphasis on Education

 

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

 

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