Is leaky gut a joke?

I addressed the issue of why most doctors consider intestinal hyperpermeability (leaky gut) a ‘quack’ diagnosis in my thesis entitled “The Implications of Intestinal Hyperpermeability.” The main reason for this (as I can see it) is due to our need for ‘scientific proof’ in our modern era of medicine. Despite the fact that doctors have understood and acknowledged the connection between gut health and overall health since antiquity (Hippocrates: “All disease begins in the gut”), the research proving this hasn’t emerged until quite recently (starting in the 1980s).

The evolution of the electron microscope in the 1960s finally allowed scientists the ability to view the microanatomy of the intestinal epithelial barrier (gut wall) for the very first time. For decades after the introduction of the electron microscope, scientists continued to believe that the enterocytes of the ‘gut wall’ were cemented together and impermeable to large macromolecules, except by way of specific transporters embedded within the enterocytes themselves. Finally in the mid 1980s, a group of Japanese scientists discovered the ‘tight junction’, proving that the paracellualr space is not cemented shut and instead contained structures that acted as doors which could open and close.With the accidental discovery of the molecule zonulin (the endogenous molecule that regulates gut permeability in all humans) by Dr. Alessio Fasano as he was engineering a vaccine against cholera in the late 1980s,  our understanding of ‘leaky gut’ changed dramatically. The discovery that zonulin modulates intestinal permeability by regulating tight junctions finally gave us the ‘scientific proof’ that we needed to connect a leaky gut with virtually all autoimmune diseases, as well as a long list of other inflammatory illnesses.

Unfortunately, most doctors trained before the 1980s are generally completely unaware of this concept. And even the modern medical student is not trained in the significant role of gut health in disease prevention. You would think/hope that our ‘experts’ would have the intuition or logic to realize that if nature put 70-80% of our immune system in and around the gut wall, that gut health and immune system dysfunction are likely highly correlated. I maintain confidence that someday our doctors will get there. In the meantime, I encourage as many doctors as I can to educate themselves about the research on zonulin and intestinal hyperpermeablity. I encourage them to familiarize themselves with the latest theory on what causes autoimmune disesase, as proposed by Dr. Alessio Fasano. The proposal that three triggers (genetically susceptibility, triggers such as gliadin/gluten or dysbiosis that trigger a leaky gut, and thirdly a leaky gut itself) are simultaneously required to initiate diseases with a zonulin biomarker (autoimmune diseases, neuro-inflammatory diseases, several types of cancer, and others) takes our understanding of ‘molecular mimicry’ a step further…and a step closer to a ‘cure’ for many diseases that have been correlated with a leaky gut. I wrote a simplified explanation of the connection between leaky gut, zonulin and autoimmunity on the Paleo Plan blog, which you can read here.

Selected References:

• Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011;91:151-75.
• Ulluwishewa D, Anderson RC, McNabb WC, et al. Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 2011;141:769-76.
• Sonier B, Patrick C, Ajjikuttira P, et al. Intestinal immune regulation as a potential diet-modifiable feature of gut inflammation and autoimmunity. Int Rev Immunol 2009;28:414-45.
• Groschwitz BS, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol 2009;124:3-20.
• Fasano A. Leaky gut and autoimmune diseases. Clinic Rev Allerg Immunol 2012;42:71-8.
• Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009;9:799-809.
• Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol 2012;10:1096-100.
• Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci 2012;1258:25-33.
• Visser J, Rozing J, Sapone A, et al. Tight junctions, intestinal permeability, and autoimmunity. Ann N Y Acad Sci 2009;1165:195-205.
• Martinez A, Perdigones N, Cenit MC, et al. Chromosomal region 16p13: further evidence of increased predisposition to immune diseases. Ann Rheum Dis 2010;69:309-11.