Project information
The gut-oral microbiome axis: how microbial metabolites influence head and neck and colorectal cancer progression

While the link between the microbiome and colorectal cancer (CRC) carcinogenesis is intuitive and has been extensively studied, the role of the gut microbiome and microbial metabolites in head and neck cancer (HNC) has been neglected or traditionally focused on the role of the oral microbiome. However, emerging evidence highlights the importance of the gut microbiome, gut health, and microbial metabolites in HNC pathogenesis. This project will focus on microbial metabolites that can enter the bloodstream and will explore the impact of microbial metabolites on the development and progression of HNC and CRC. These cancers are influenced by both genetic and environmental factors, with recent evidence pointing to the microbiome as a key player in tumour behavior. The research will focus on metabolites produced by gut bacteria, namely short-chain fatty acid (butyrate), trimethylamine N-oxide (TMAO), deoxycholic acid (DCA), and indole-3-acetic acid (IAA), which have been shown to affect cancer cell proliferation, migration, and resistance to therapy, while also acting as messengers that affect gene expression, immune cell function, and overall immune homeostasis. The study seeks to investigate how the gut microbiome impacts cancer through local effects in CRC and systemic effects in HNC. Particular interest would be in the gut-oral axis by investigating how gut metabolites interact with tumour cells and cancer-associated fibroblasts (CAFs), potentially activating pro-tumorigenic signaling pathways that influence cancer cell progression. These findings could lead to more personalized cancer treatment strategies and improved patient outcomes, emphasizing the potential for microbiota-based interventions. The study is in line with current research efforts to understand the role of the tumour microenvironment, and expects to provide critical preliminary data that will be used for future grant applications.