Leaky gut syndrome: Causes of leaky intestinal barrier and disease associations

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Leaky Gut Syndrome

Gut has to perform multiple complex functions including digestion, absorption and fighting off harmful stimuli. A single layer of cells separates the body from trillions of bacteria and other potentially harmful substances in the intestinal lumen. Intestinal is a semipermeable barrier that allows for absorption of nutrients while wards of harmful stimuli. This gut barrier is complex, and is size and charge specific.

The intestinal barrier is not static, rather it is dynamic anatomic and functional structure and keeps adjusting itself and its permeability based on circumstances.

The intestinal barrier is made up of variouys components, wherein Tight Junctions play a sentinel role of sealing the gaps between the intestinal cells. Tight junctions contain various proteins regulated by zonulin that allows for opening and closing of tight junctions between intestinal cells as needed.

Optimal health requires that this intestinal barrier continue to function constantly 24/7 against potentially noxious stimuli like bad bacteria, large semi-digested allergenic foods as well as toxins. Imperfections can occur either transiently or for sustained periods.

Causes of intestinal hyperpermeability or leaky gut syndrome

Leaky gut or increased intestinal permeability may occur to to a wide variety of causes. The role of gut bacteria, inflammation and genetic predisposition is intertwined in increasing permeability or leakiness. Life style and environmental factors play an important role:

• Drugs like NSAIDs (aspirin type medications), antbiotics, oral iron
• Dysbiosis (unhealthy balance of good versus bad bacteria in gut)
• Small intestinal bacterial overgrowth
• Infections even as simple as viral infection or gastroenteritis
• Emotional stress
• Allergenic diet for example gluten in susceptible subjects
• Unhealthy cooking practices (Fried food more than roatsed food more than boiled food)
• Unhealthy food additives and preservatives
• Alcoholism
• Toxins
• Ischemia (low blood supply to gut)
• Chemo- and radiation therapy
• Sustained rigorous exercise

Diseases associated with leaky gut syndrome and/or abnormalities (leakiness) of Tight Junctions

Inflammatory bowel disease (Ulcerative colitis and Crohn’s disease)	Chemotherapy induced mucositis	Chronic fatigue syndrome
Irritable bowel syndrome	Liver cirrhosis	Hepatic encephalopathy
Celiac disease	Diabetes	Infections in liver cirrhosis
Collagenous colitis	Autism	Depression
Intrahepatic cholestasis of pregnancy	Eczema	Total parenteral nutrition
Intestinal infections	Asthma	Sepsis and multi-organ failure
Food allergies	Nonalcoholic fatty liver disease	NSAID (Aspirin like drugs) induced gut injury
Graft versus host disease	Schizophrenia	Congestive heart failure
Multiple sclerosis	Ankylosing spondylitis	Chronic inflammatory demyelinating polyneuropathy

Why is everyone not affected? Why do different diseases occur in different people?

The reasons for multiple diverse manifestations of leaky gut are manifold and include the gut bacteria and the genetic predispostion along with the complex environmental factors involved.

If the genetic predisposition is high and so is the imbalance of bad versus good gut bacteria on top of sum total of environmental stimuli (stress, bad and/or allergenic diet, antibiotics etc), the disease is more likely to occur. Conversely, if genetic predisposition is low and the person has a healthy lifestyle, thbe likelihood of disease is low.

Based on the same reasons above, the manifesttations may be different. For example, if exorphins (large semi-digested large proteins particles) are absorbed and can interact with receptors in brain, nervous system manifestations ensue.

Absorption of antigenic foreign substances can induce an immune defense in the form of antibody response. These antibodies may then sometimes recognize body's own tissues as foreign and can start destroying these tissues causing an autoimmune disease.

Select citations for Leaky gut

Fasano 2011	Catalioto et al 2011	Salim et al. 2011
Douek 2007	Fink 1990	Maes 2011
White 2003	Clayburgh 2004	Shen 2009

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Comments

[Kathy Garolsky]

Thanks for sharing this.I enjoyed reading it.Thanks