Fig. 3: The NLPR6 and microbiota–epithelium interface.

Bacteria-derived TLR agonists such as LPS, lipid A, and flagellin activate the Myd88-ROS pathway to activate the NLRP6 inflammasome in sentinel goblet cells. Activated NLRP6 facilitates the exocytosis of muc2 from goblet cells to form a physical barrier above the epithelium. In steady-state condition, microbiota such as Muribaculaceae and genus Adlercrutzia contribute to “impenetrable” inner mucus layer phenotype. The decrease in abundance of such microbiota could led to “penetrable” inner mucus layer characterized by a dysfunctional inner mucus layer. ROS: reactive oxygen species; LPS: lipopolysaccharides.