Fig. 1.

Leaky Gut Syndrome: On the left is shown a depiction of the normal gut, with colonization by varies bacterial species that remain in the lumen. Gut epithelial cells (shown in pink) are tightly attached to each other with tight junctions that prevent penetration of bacteria or their soluble products such as LPS into the submucosal tissues and thence into the bloodstream. Dendritic cells (DC) sample the gut contents to obtain bacterial antigens that are presented to T cells. Homeostasis is maintained by Tregs that prevent excess inflammation resulting from over-activation of the immune response by commensal microbes. This effect of Tregs is driven in part by their secretion of the immunoregulatory cytokine IL-10, which acts to suppress inappropriate activation by effector T cells (Teff). On the right is a depiction of a leaky gut. In the leaky gut, tight junctions between gut epithelial cells are partially disrupted, allowing bacteria and their products to penetrate into the submucosal tissue and then travel via the bloodstream to other tissues. The presence of bacteria and their products activates DCs and intestinal epithelial cells via TLR receptors. DCs can then drive formation of Th17 ​cells that secrete the pro-inflammatory cytokine IL-17. Treg activity in a leaky gut is insufficient to suppress immune activation due to the overwhelming proinflammatory signals. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)