Full title: A Prospective, Longitudinal Study to Investigate the Effect of Thermal Injury on Intestinal Permeability and Systemic Inflammation (HESTIA)

Aims: This longitudinal, prospective study aims to establish the magnitude and time course of changes in intestinal permeability.

Establish the optimal method for assessment of intestinal permeability in thermally injured participants.

Describe the participant population most likely to benefit from a new medicinal product which could prevent changes in intestinal permeability.

Improve our understanding of the links between intestinal damage, changes in the gut microbiome and microbial translocation to the systemic circulation following thermal injury.

The key factors of interest in this study are to understand the impact of thermal injury on intestinal permeability in thermally injured participants compared to healthy participants; and to understand the changes in intestinal permeability over time.

Background: Following a large burn, inflammation in the body can damage the gut lining. This means the gut becomes leaky, allowing bacteria and other substances to enter the blood where they can cause more inflammation and can contribute to organ failure and infections.

In order to understand this process better, this study asks patients with burns to have measurements taken of their gut health. The study will also be looking at the bacteria in samples of faeces and for signs of inflammation in urine samples.

Process: Approximately 15 eligible healthy participants and 25 thermally injury participants will be included. The sugar test material (STM) comprises of Lactulose, Mannitol and Sucralose and will be intermittently administered enterally to all the participants. The full duration of the study for healthy participants will be approximately two weeks and 6 months for thermally injured participants. In order to enter this study thermally injured participants will be required to co-enroll in this study and an allied study entitled: A Multi-Centre, Prospective Study to Examine the Relationship between Neutrophil Function and Sepsis in Adults and Children with Severe Thermal Injury (SIFTI-2)