Leaky Gut

There is much information on leaky gut, and I have read through a good share of it.   I found Leaky Gut Syndromes: Breaking the Vicious Cycle by Leo Galland, MD from the Foundation of Integrated Medicine to be an interesting read.  I actually have had it in my file cabinet for almost a year.   I recently re-read it and many things began to stand out even more.  

The GI tract functions as a part of the immune system, providing protection by complex mechanisms working together: 

• Intestinal secretions (primarily mucus and secretory IgA)
• Mucosal epithelium
• Intramural lymphocytes

"Compromised intestinal barrier function can also cause disease directly, by immunological mechanisms. Increased permeability stimulates classic hypersensitivity responses to foods and to components of the normal gut flora; bacterial endotoxins, cell wall polymers and dietary gluten may cause "non-specific" activation of inflammatory pathways mediated by complement and cytokines.  In experimental animals, chronic low-grade endotoxemia causes the appearance of auto-immune disorders."

He goes on to clarify how leaky gut syndromes are disorders due to increased intestinal permeability (which is the medical speak for leaky gut), noting that hyperpermeability may play a primary role in the evolution of the disease or it may be a secondary consequence which "causes immune activation, hepatic dysfunction, and pancreatic insufficiency, creating a vicious cycle."  

A key point to this whole article, to me, is when he states "Unless specifically investigated, the role of altered intestinal permeability in patients with Leaky Gut Syndromes often goes unrecognized". 

I found it interesting when he defines his theories on what triggers leaky gut: infections, ethanol, and non-steroidal anti-inflammatory drugs, also hypoxia of the bowel (as occurs as a consequence of open heart surgery or of shock), elevated levels of reactive oxygen metabolites (biliary, food-borne or produced by inflammatory cells), and cytotoxic drugs. 

He then goes on to delineate the Four Vicious Cycles:

1. Allergy:
• relationship is complex and circular
• studies show that an increase in intestinal permeability is important in the pathogenesis of food allergy and is also a result of food allergy.
2. Malnutrition:
• disruption of the cell junctions increases absorption of large molecules from foods.
• if cells are damaged, there is decreased absorption of nutrients through them, which results in less cell growth (malnutrition). 
• intestinal cells slough off and grow new every 3-6days, this requires quality nutrition/calories
• if intestinal cells are damaged and their nutritional needs are not met, increased intestinal permeability worsens. 
3. Bacterial Dysbiosis:
• Dysbiosis is caused from a dysfunction in the microbes of the gut that cause a state of disease and change the metabolic or immunological responses from the gut. 
• Sites this article: Intestinal Dysbiosis and the Causes of Disease as reference for review.
• Immune responses to the normal gut flora is a form of dysbiosis that has been connected to the development of Crohns and ankylosing spondylitis. 
• Research findings have suggested that bacterial immune responses is the early complication of altered permeability and exacerbates hyperpermeability by inducing inflammatory enteropathy.
4. Hepatic Stress:
• The liver works to remove macromolecules released into the bloodstream due to leaky gut, and to oxidize intestinal toxins.
• This can result in damage to liver cells and excretion of by-products into bile, capable of damaging bile ducts and backing up into the pancreas. 
• The toxic bile damages further the mucosa of the intestine, with exacerbates hyperpermeability.

He then goes on to describe practical approaches and therapies for treatment of leaky gut disorders.  As well as a table of the diseases associated with increased intestinal permeability and symptoms associated with it. 

Approaches include:

• Lactulose/Mannitol tests
• IgG titres

Therapy's include:

• Probiotics
• Essential Fatty Acids
• Fiber
• Other alternative/complimentary supplements such as epidermal growth factor, Glutamine, Glutathione, and Gamma oryzanol.  

Noting that these should not be used as primary therapy and that natural methods should be utilized first, ensuring a diet rich in vitamins and minerals to support healthy intestinal growth adn repair "Avoidance of enterotoxic drugs, treatment of intestinal infection or dysbiosis, and an allergy elimination diet of high nutrient density that is appropriate for the individual patient are the primary treatment strategies for the Leaky Gut Syndromes".

He concludes: "Altered intestinal permeability is a key element in the pathogenesis of many different diseases. Hyperpermeability initiates a vicious cycle in which allergic sensitization, endotoxic immune activation, hepatic dysfunction, pancreatic insufficiency and malnutrition occur; each of these increases the leakiness of the small bowel.
Effective treatment of the Leaky Gut Syndromes requires several components:

1. avoidance of enterotoxic drugs and allergic foods,
2. elimination of infection or bacterial overgrowth with antimicrobials and probiotics,
3. dietary supplementation with trophic nutrients.

 Direct measurement of intestinal permeability allows the clinician to plan appropriate strategies and to gauge the effectiveness of treatment, using objective parameters."