Alessio Fasano, M.D.: The Gut is Not Like Las Vegas

The intestinal epithelium is the largest mucosal surface providing an interface between the external environment and the mammalian host. Its exquisite anatomical and functional arrangements and the finely-tuned coordination of digestive, absorptive, motility, neuroendocrine and immunological functions are testimonial of the complexity of the gastrointestinal system. Also pivotal is the regulation of molecular trafficking between the intestinal lumen and the submucosa via the paracellular space. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions (TJ), structures whose physiological modulation is mediated, among others, by the TJ modulator zonulin. The structural and functional characteristics of intercellular TJ and the protean nature of the intestinal content suggest that the gut mucosa represent the “battlefield” where friends (i.e., nutrients and enteric microflora) and foes (i.e., pathogenic microorganisms and their toxins) need to be selec