Targeting toxic gut lymph to treat acute disease

Acute and critical illness (ACI) are usually managed in emergency and intensive care settings, and includes sepsis, trauma, haemorrhagic shock and pancreatitis. 30% of patients die due to progression of ACI from an acute systemic inflammatory response syndrome (SIRS) to multiple organ dysfunction syndrome (MODS). Current management of AD is supportive and includes fluid resuscitation, enteral feeding, antibiotics and organ support. More effective and specific treatments are critically needed.
Recent findings in our collaborators lab have identified gut-lymph as a source of toxic factors that promote SIRS and MODS. According to the gut-lymph hypothesis blood flow to abdominal organs is reduced in ACI. This results in gut ischemia and breakdown, and the release of toxic factors that drain into the gut-lymph. Toxic gut-lymph flows into the thoracic lymph, bypasses the liver and enters the systemic circulation via the subclavian vein. Toxic gut-lymph subsequently damages vital organs remote from the gut.

The project aims to:

1. Develop novel drug delivery systems to target gut-lymph to treat ACI

2. Demonstrate that gut-lymph targeted delivery systems facilitate improved treatment of experimental ACI

This project addresses the need for effective and disease-specific treatments for ACI via the development of approaches to treatments that target ‘toxic’ gut-lymph.

Interdisciplinary Research

The project will involve interaction with our drug delivery and chemistry teams and ACI clinicians Prof John Windsor and Anthony Phillips in Auckland. The student will receive training in drug delivery and pharmacokinetics, cell culture, analysis (LC-MS-MS) and ACI models.

Placement model

The student may spend up to 4 months in our collaborators lab in Prof John Windsor and Anthony Phillips’ labs at the University of Auckland running experiments in ACI models.