What is it about?

Current treatment for sepsis is aimed at eradicating infection. However, sepsis occurs when the body’s response to an infection injures its own tissues and organs. Currently there are no treatments aimed at the body’s response to infection. The tight junction protein claudin-2 helps control movement of small molecules from the gut lumen to the rest of the body by travelling in between cells in the intestine. Previous work has shown that the gut becomes leaky in sepsis, allowing for increased movement of these small molecules, yet the mechanisms underlying this and its importance remain poorly understood. Here we identify that claudin-2 is increased in septic patients. Further, we found that eliminating claudin-2 improves survival in septic mice due, at least in part, to its effect on the bacteria that live inside the gut lumen.

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Why is it important?

Sepsis is responsible for nearly 20% of deaths worldwide. Current there are no therapies aimed at the body’s response to infection (as opposed to the infection itself) despite the fact that patient’s body plays a critical role in the development of organ failure and death from sepsis. We found that claudin-2 levels are increased in the small intestine in patients who had surgery for intestinal perforation compared to patients who underwent elective intestinal surgery. Importantly, mouse studies showed that these increases in claudin-2 contribute to intestinal damage and inflammation and are associated with increased chance of dying after sepsis. This suggests that targeting increased claudin-2 may be an attractive therapeutic target in septic patients.

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This page is a summary of: Claudin-2 upregulation enhances intestinal permeability, immune activation, dysbiosis, and mortality in sepsis, Proceedings of the National Academy of Sciences, February 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2217877121.
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