Gastrointestinal (GI) symptoms affect up to 45% of the world’s population and for some patients the reason behind the symptoms is unclear, as available tests and routine bowel scans reveal no known abnormalities. It has long been recognised that the incidence of diseases such as inflammatory bowel disease (IBD) differs between male and females (e.g. Crohn’s disease is more prevalent in females). Additionally, within individuals, specific regions of the GI tract are often more affected by disease than others. The nature and significance of these sex and region-specific differences are currently unknown. Hence, there are unmet diagnostic and therapeutic needs with a potential to impact a vast number of people worldwide.
We have discovered in fruit flies that the shape of the gut as it packs into the abdomen is non-random. This shape matters for communication between organs and also impacts the reproductive potential of females. Additionally, gut shape differs between males and females, which means the potential signalling between the gut and neighbouring organs differs by sex. This opens up the possibility that a similar state is found in humans which may explain some of the sex and region-specific differences found in GI disease incidence. The aim of our three-year project is to repurpose the techniques for analysing the fruit fly gut to analyse the shape of the human GI tract. We want to map GI shape and its contact with neighbouring organs in three-dimensions to shed light on whether there are differences between men and women and how GI shape might impact disease.
MR imaging is routinely used in the evaluation of GI disorders such as IBD. This involves a trained radiologist visually examining the scans to identify abnormalities. However, a lot of information about GI shape is present in these scans but unutilised. We will use the MR images from the UK Biobank to identify features of GI shape which might be predictive or diagnostic of disease. We will compare GI shape with data about people’s lifestyle and health collected by the UK Biobank to identify features of GI shape which might be predictive of health or disease. This may aid clinicians to diagnose or predict GI diseases from MR images. Mechanistic understanding of the sex and region-specific biases in GI disease will not only shed light on historically under investigated research areas, but it will also pave the way towards precision therapies for these disorders.