There are close to 1700 lives saved by solid organ transplant (SOT) in Australia each year. Infection and immunological complications represent the major determinants of morbidity and mortality and also drive transplant-associated costs so there is an economic as well as clinical imperative for investigating novel approaches to predicting and treating these complications despite existing strategies. Specific bacterial microbiome signatures have been associated with risk of infections and immunological complications after transplant in previous studies. Risk for acute cellular rejection and blood stream infection after liver transplant have both been correlated with microbiome diversity in small single centre cohorts. But understanding of the mechanisms underlying interactions between bacterial and non-bacterial microbial complements, infectious risk and graft survival is currently limited. Definition of these components in well-defined transplant cohorts is essential to capitalise on any opportunity they may present for translation into targets of novel diagnostics and therapeutics.

Intestinal transplantation is considered standard of care for patients with irreversible intestinal failure who can no longer be sustained on parenteral nutrition. The intestine however, when compared to other solid organs, tolerates transplantation poorly, as it is very vulnerable to damage from interruption to blood supply (ischaemia). Donation after circulatory death (DCD) is a more commonly used donation pathway in Australia, with >50% of liver donor offers to Austin Health being DCD. DCD pathway increases ischaemia and for this reason is deemed too high risk for intestinal transplantation. Machine perfusion can be used to minimise ischemia to the organ, and whilst it is routinely used in other solid organs, there is currently no clinically approved perfusion device for intestinal preservation. In this feasibility study we aim to obtain full length human small intestine from deceased organ donors to study intestinal function using a machine perfusion platform.

This study investigates a new method to expand the pool of suitable donor livers for transplantation. Using a technique called normothermic machine perfusion—which keeps the liver functioning outside the body under near-normal conditions—researchers will test whether specific enzymes can safely remove blood group antigens (A or B) from donor livers. Successful conversion to a universal blood group type could allow these organs to be transplanted into recipients of any blood group, overcoming a major compatibility barrier and potentially increasing the number of viable liver transplants available each year.