Dietary fibre, the gut microbiome and cancer immunotherapy: from observation to a rational dietary intervention

Immune checkpoint blockade (ICB) has revolutionised cancer care; however responses remain unpredictable, and patients are at risk of potentially-severe autoimmune side effects that can affect any organ system. There is a desperate patient need for new strategies to enhance immune responses and mitigate ICB toxicity. A promising emerging avenue is dietary modulation of the ‘gut microbiome’- the trillions of microorganisms (predominantly bacteria) that reside in our intestines. Our preceding work has shown that particular bacteria that ferment dietary fibres are enriched in ICB responders; the putative mechanism being increased fermentation products such as short chain fatty acids. This is corroborated by a number of observational studies linking patient dietary fibre intake with response; however, less is known about the relationship between dietary fibre, gut microbiota and ICB toxicity. Furthermore, practical approaches to use rational dietary-fibre based strategies to improve cancer care are still in development. This PhD will combine analysis of patient dietary intake from an ongoing observational study at Eastern Health (‘Microbiome and dietary correlates of Immuno-Oncology toxicity and response’ (MicroIO)) with conduct of a multicentre pilot randomised controlled trial in patients with melanoma undergoing standard of care ICB treatment (‘A Fermentable fibre intervention for patients with melanoma’ (Ferm-mel)). Ferm-mel will be run at three leading Monash University-affiliated tertiary health services (Eastern Health, Bayside Health and Monash Health), and involves provision of a rationally-designed fermentable fibre snack menu or matched, isocaloric controls with dietetic counselling to improve fibre intake. Monash University is well equipped with state-of-the-art infrastructure for conducting feeding studies, including a commercial kitchen (BASE), and unique access to a food composition database for FODMAPs and resistant starch (https://www.monashfodmap.com/). The student will lead dietary assessment and nutritional analysis for both studies, as well as dietary product production, quality control, delivery and participant counselling for Ferm-mel. They will work closely with a team of oncologists, dietitians, microbiome scientists and bioinformaticians on both projects. This project is particularly suited to a dietitian interested in cancer, clinical research, the gut microbiome and the development of practical, scalable nutritional interventions or products. SKILLS - The candidate will develop expertise in: * The link between diet, the microbiome and cancer immunotherapy * The conduct of investigator-initiated dietary clinical research in people with cancer, including both an observational and interventional clinical trial * Methods to analyse the gut microbiome, including shotgun metagenomic sequencing, metabolomics and anaerobic culture (this will be well-supported by microbiome scientists in the Gunjur laboratory). * The analysis of diet & nutritional data, and its integration with other clinical, gut microbiome and immune datasets. This will include both basic and advanced statistics, advanced data visualisation, and cutting-edge gut metagenomic analysis, and will be well supported by microbiome scientists, bioinformaticians and a biostatistician within the Gunjur laboratory and Eastern Health Clinical School.