F-actin dynamics couples sphingolipid metabolism to epithelial barrier integrity in chronic colitis

In IBD, the disruption of the gut barrier causes fluid loss and persistent immune response. Understanding the cellular events underlying epithelial barrier disruption during chronic inflammation is essential for targeting increased intestinal permeability.

Filamentous actin (F-actin) destabilization accompanied by metabolic dysfunction has previously been reported in the Muc2 knockout colitis model; however, the mechanistic contribution of these defects to chronic intestinal barrier loss remains unclear. Here, we identify impaired cytoskeleton dynamics as a critical driver of intestinal barrier dysfunction in chronic colitis. An imbalance between polymeric and monomeric actin disrupts the epithelial barrier in both a 3D organoid system and in vivo.