Predicting your gut feeling: bench-to-bedside immunology for blissful bowels

The gut is a complex environment that is tightly controlled to achieve homeostasis. Interactions between immune cells, microbes and gut cells are crucial, and dysregulation of these can lead to disease. Inflammatory bowel diseases (IBD) affect over 20,000 people in New Zealand, and Otago has one of the highest incidence rates in the world.

Colorectal cancer (CRC) has the second highest cancer mortality in New Zealand, with 1200 deaths every year. How can we use our knowledge of the immune system and current techniques to have a real effect on patient outcomes in the clinic? Cornering colorectal cancer The infiltration of immune cells into colorectal cancers has been established as a more accurate measure of patient disease-free survival than existing staging methods. This has recently been commercialised as the Immunoscore, costing upwards of NZD 4500 per patient and needing a certified lab.

Low- and middle-income countries, where Immunoscore isn’t available or the cost is prohibitive, have rapidly increasing rates of CRC and would benefit greatly from a cheaper Immunoscore-alike. Here, we describe a freely available method to immunoscore CRC resections that performs well in a local cohort. Inhibiting inflammatory bowel disease Crohn’s disease is an IBD that can significantly decrease quality of life. Inflammation in the gut can lead to many symptoms, including fatigue and diarrhea. The complete aetiology of the disease is unknown, but it is clear that immune, microbial, gut barrier and environmental factors all play a role.

Treatment with anti-tumour necrosis factor (anti-TNF) monoclonal antibodies is effective in some patients but has a non-response rate between 13 – 40%. Human intestinal organoids (HIOs) are miniature three-dimensional organs grown in culture that more accurately represent the epithelium of the gut compared to traditional cell culture. They represent an opportunity to collect clinically relevant and patient-specific results in the lab.

Here, we present an organoid model system to measure gut barrier integrity in vitro to recapitulate clinical outcomes of anti-TNF responsiveness. Lastly, the lungs Organoids can also be generated from other tissues, such as from the airway.

New treatments will be crucial in reducing the global respiratory infection burden, responsible for 5% of global mortality in 2019, and increasing with the COVID-19 pandemic. Here, we propose the use of virally infected airway organoids co-cultured with immune cells to model lung disease.