Reverse Engineering the Inflammatory Cascade

My central theory about the cause of IBD, and therefore its reversal, revolves around the gut microbiome (GM). The gut microbiome is the total collection of microorganisms that inhabit the gastrointestinal tract which include bacteria, viruses, protozoa, and fungi (1). The GM is known to play a large role in the proper functioning of the immune system, and increasingly in the pathogenesis of IBD (2). Research has shown that the characteristic chronic inflammation of IBD is due to intestinal hyperpermeability of the intestinal epithelial cells in the mucosa of the small intestine and colon (3). Intestinal hyperpermeability, commonly called leaky gut, allows pathogenic entities, such as undigested food particles, allergens, toxins and microorganisms, to cross the gut barrier unchecked and enter the systemic circulation. This causes the immune system to respond hyperactively in order to neutralize the pathogenic entities, resulting in chronically inflamed intestines (3).

When healthy, intestinal epithelial cells of the mucosa are bolted together by dynamic protein structures called tight junctions (TJ). These TJs allow the paracellular pathways of intestinal epithelial cells to be selectively semipermeable; allowing nutrients to diffuse into the bloodstream while excluding pathogenic entities and microorganisms (4). Faulty functioning TJs result in intestinal hyperpermeability, which results in a hyperactive immune response, and then can ultimately lead to IBD if the inflammation becomes chronic (2,3,4). These vital gatekeeping proteins, that influence intestinal permeability, are regulated by microorganisms in the GM through a variety of signaling mechanisms (5,6,7).

When the GM is in eubiosis, a greek word that can be translated to mean “good life”, the microorganisms in the GM are appropriately balanced and are able to properly perform all of their specific functions relating to human metabolism, physiology, and immunology (5,8). This includes regulating and restoring the TJs (9). This is the desirable state we want the GM to be in. When the GM is in dysbiosis, or imbalance, TJ regulation can be interrupted, resulting in the cascade that leads to IBD (4,5,8,9,10).

Since GM dysbiosis is what causes TJ regulation to be interrupted, dysbiosis is thus the root cause of intestinal hyperpermeability. Intestinal hyperpermeability results in a hyperactive immune response to invading pathogens, and can ultimately result in chronic inflammation and the pathogenesis of IBD (3,9,11). By simply reverse engineering the disease, moving the GM towards eubiosis should help to reestablish proper TJ functioning between intestinal epithelial cells, decrease intestinal hyperpermeability, and in so doing, decrease the hyperactive immune response and inflammation, and thus reverse IBD (2,3,4,12).

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