Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Auto
Interesting paper linking many disease states to gut health
http://physrev.physiology.org/content/91/1/151.long
The gastrointestinal tract has been extensively studied for its digestive and absorptive functions. A more attentive analysis of its anatomo-functional characteristics, however, clearly indicates that its functions go well beyond the handling of nutrients and electrolytes. The exquisite regional-specific anatomical arrangements of cell subtypes and the finely regulated cross-talk between epithelial, neuroendocrine, and immune cells highlights other less-studied, yet extremely important, functions of the gastrointestinal tract. Of particular interest is the regulation of antigen trafficking by the zonulin pathway and its activation by intestinal mucosa-microbiota/gluten interactions. These functions dictate the switch from tolerance to immunity and are likely integral mechanisms involved in the pathogenesis of inflammatory and neoplastical processes.
The classical paradigm of inflammatory pathogenesis involving specific genetic makeup and exposure to environmental triggers has been challenged recently by the addition of a third element, the loss of intestinal barrier function. Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food-derived environmental triggers or changes in gut microbiota all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer. This new theory implies that once the pathological process is activated, it is not auto-perpetuating. Rather, it can be modulated or even reversed by preventing the continuous interplay between genes and the environment. Since zonulin-dependent TJ dysfunction allows such interactions, new therapeutic strategies aimed at reestablishing the intestinal barrier function by downregulating the zonulin pathway offer innovative and not-yet-explored approaches for the management of these debilitating chronic diseases.