Endocrine Abstracts

The term Leaky Gut Syndrome (LGS) describes a collection of a range of symptoms, including abdominal pain, bloating, recurring diarrhoea, bloody stools and weight loss, when a diagnosis has not been, or cannot be, made. It can be associated with inflammatory bowel disease (IBD), celiac disease, chemotherapy and radiation therapies, and endocrine conditions including obesity and diabetes. The common underlying features of LGS are gut inflammation and an increase in gastrointestinal tract permeability. Currently, gut permeability is measured in two broad approaches, absorption from the gut to the blood or biopsy. Not only can these procedures be highly invasive and uncomfortable, but they only allow very small and limited sampling, and may not distinguish between specific diseases. We have tested a novel methodology in rodents that non-invasively measures gut permeability in real time with the ability to spatially map the level of permeability throughout the gut. This is achieved through the use of ultrasound imaging and phase change contrast agents. In their condensed state nanodroplets are undetectable and ~100 nm in diameter. Nanodroplets are injected into the bloodstream and remain within the blood vessels that vascularise healthy tissues. However, in diseased tissue these nanodroplets can extravasate and become trapped within the tissue. Once the nanodroplets remaining in the circulation have been cleared, these extravasated droplets can be activated through acoustic pressure, providing a high contrast signal. This signal thus highlights areas of high vessel wall permeability. Within the gastrointestinal tract, our data show that this method provides a non-invasive measure of LGS that we have validated using microscopy. Ultrasound is cost efficient, non-ionising and provides real time results, and this represents a non-invasive tool to quantify gut permeability and diagnose LGS which has the potential to change the monitoring and treatment of the millions of people it affects worldwide.