‘Leaky gut’ in hematological malignancies☆

In humans, the intestinal epithelium is a single layer of cells that constitutes one of the most important barriers between internal and external environments. The so-called ‘intestinal barrier’ (IB) is a dynamic structure composed of different types of cellular junctions that can be regulated by physiological and pathological stimuli, and act as a selective barrier to antigens and pathogens. Physiological mechanisms that regulate IB function are important for nutrient absorption and antigen permeation, with potential roles in the regulation of tolerance to non-self antigens.1 However, pathological stimuli such as pathogens, cytokines and immune cells are also capable of affecting IB function as demonstrated in studies about tumor necrosis factor alpha (TNF)-mediated IB disruption.2 Accordingly, a model known as ‘leaky gut syndrome’ has emerged based on the concept that TNF-mediated cycles of increased IB permeability may lead to translocation of macromolecules from the lumen into the lamina propria, and to amplification of mucosal immune activation. In the absence of appropriate regulatory signals, this vicious cycle may result in local or systemic immune-mediated diseases, such as Celiac disease, Crohn’s disease, food allergies, and even type-1 diabetes mellitus.3