fluorescence spectroscopy for gut permeability assessment

Conditions: Development and Validation of Gut Permeability Sensor; Permeability; Increased; Celiac Disease; Inflammatory Bowel Diseases; Liver Diseases; HIV/AIDS

Summary: this research aims to develop portable devices - known as fluorescence spectrometers - to monitor the leakage of fluorescent dyes out of the gut into the blood stream. these devices will measure the leakiness (permeability) of the gut in a non-invasive manner and will provide an early warning that patients are at risk of infections caused by the unwanted flow of bacteria from the intestine to the rest of the body.

"leaky gut" - or, increased permeability of the intestine - involves the leakage of certain intestinal constituents (e.g. endotoxins or even bacteria) from the gut into the rest of the body. this condition is associated with many widespread diseases including coeliac disease, inflammatory bowel disease, hiv, liver cirrhosis, sepsis and environmental enteric dysfunction (eed). it has a considerable impact on quality of life and, in extreme cases (e.g. sepsis), it can even lead to death. furthermore, in the developing world (as part of eed), it severely hampers the mental and physical development of young children. thus, new devices that can help us to learn more about leaky gut and more accurately monitor its effects are urgently needed. in this project, patients will drink a small dose of a fluorescent dye. then, by shining light on the patients' skin and recording the color and brightness of the light (fluorescence) that comes back, it will be possible to measure the amount of dye that has leaked into the blood (indicating the likelihood that bacteria are escaping from the gut and causing infections). we refer to this as a "spectroscopic gut permeability test." we will also ask patients to take a traditional permeability test (known as a peg permeability test) so that we can validate our new sensor. overall, this research will deliver vital information that will improve our understanding of leaky gut and help guide the development of treatments for the many diseases in which it occurs.

Eligibility criteria:
inclusion criteria: * ability to give informed consent * aged 18 years or above * no evidence of prior adverse reactions to fluorescein, icg, dextran or peg * no evidence of prior adverse reactions to iodine (for icg experiments only) * for healthy volunteers: healthy with no active gi/liver disease (or other condition in which increased gut permeability is expected, e.g. hiv) and no antibiotics taken within the previous four weeks. * for cases: exhibiting symptoms of gi, liver or other diseases (e.g. hiv) in which increased intestinal permeability is expected. * for ophthalmology patients recruited in stage 1: healthy (i.e. as described above for healthy volunteers) and prescribed to have an ophthalmic angiography with an intravenous injection of either fluorescein or icg. exclusion criteria: * unable to give informed consent * aged \<18 years * previous adverse reaction to fluorescein, icg, dextran or peg * known allergy to iodine (for icg experiments only) * pregnancy (in stage 1 this will be at the discretion of the patient's ophthalmologist) * breastfeeding (in stage 1 this will be at the discretion of the ophthalmologist)

Keywords: gut permeability fluorescence spectroscopy wearable sensor leaky gut