• Tetsuya Yumoto, Takehiko Oami, Zhe Liang, Eileen M Burd, Mandy L Ford, Jerrold R Turner, and Craig M Coopersmith.
• Department of Surgery and Emory Critical Care Center, Emory University, School of Medicine, Atlanta, Georgia, USA.
• Shock. 2024 Dec 3.

AbstractSepsis induces intestinal hyperpermeability, which is associated with higher mortality. Occludin is a tight junction protein that plays a critical role in regulating disease-associated intestinal barrier loss. This study examined the role of intestinal occludin on gut barrier function and survival in a pre-clinical model of sepsis. Intestinal epithelial-specific occludin knockout (occludin KOIEC) mice and wild type controls were subjected to intra-abdominal sepsis and sacrificed at pre-determined endpoints for mechanistic studies or followed for survival. Occludin KOIEC mice had a significant increase in intestinal permeability, that was induced only in the setting of sepsis as knockout mice and control mice had similar baseline permeability. The worsened barrier was specific to the leak pathway of permeability, without changes in either the pore or unrestricted pathways. Increased sepsis-induced permeability was associated with increased levels of the tight junction ZO-1 in occludin KOIEC mice. Occludin KOIEC mice also had significant increases in systemic cytokines IL-6 and MCP-1and increased bacteremia. Further, occludin KOIEC mice had higher levels of jejunal IL-1β and MCP-1 as well as increased MCP-1 and IL-17A in the peritoneal fluid although peritoneal bacteria levels were unchanged. Notably, 7-day mortality was significantly higher in occludin KOIEC mice following sepsis. Occludin thus plays a critical role in preserving gut barrier function and mediating survival during sepsis, associated with alterations in inflammation and bacteremia. Agents that preserve occludin function may represent a new therapeutic strategy in the treatment of sepsis.Copyright © 2024 by the Shock Society.

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