Figure 6.

Complex relationship of epithelium defect, microbiome translocation and mucosal inflammation. Under a germ-free environment, Muc2 misfolding in epithelial cells initiate inflammatory signals directly, but the signal is only significantly amplified by the presence of gut microbiota and immune cells in a conventional environment. In turn, the inflammation and microbiota translocation (or TLR leakage) can exacerbate Muc2 misfolding and ER stress resulting in mucus layer depletion and increased bacteria translocation. This sets a feed-forward cycle for progressive intestinal inflammation in Winnie mice. Figure created using BioRender