Fig. 1

Schematic representation of gut barrier dysfunction in critical illness. Under basal conditions, TJs, composed of key proteins such as members of the claudin family, occludin, ZO-1, and JAM-A, and the perijunctional actin-myosin ring, maintain gut integrity and prevent the translocation of harmful substances. Activation of MLCK enhances the phosphorylation of perijunctional myosin light chains, ensuring cytoskeletal contraction and the subsequent opening of TJs. During critical illness, TJs are compromised, leading to increased gut permeability through three distinct pathways. The pore pathway allows passage of small ions and water, while the leak pathway allows larger molecules such as lipopolysaccharide (LPS). Additionally, the TJ-independent unrestricted pathway occurs at areas of epithelial damage enabling the translocation of whole bacteria. These changes are often accompanied by a shift in the microbial community towards dysbiosis with invasive pathogens. The disruption of barrier function increases the chance of microbes and microbial-derived products having distant effects, potentially triggering systemic inflammation through mucosal immune activation and leading to organ dysfunction