LAUSR

Simple Summary A symbiotic relationship with the host gut microbiome influences the immune system’s development, functions, and activities. In the mucosa, the gut microbiome mediates several immune activities such as the induction of naïve T-cells differentiation, production of cytokines, and myeloid cells activation. The gut-immune interaction and GI cancer development were investigated more recently. Understanding the interaction’s underlying mechanism provides insight to use them as potential anti-cancer targets. Even though multiple reports support the role of gut-immune interactions in targeting cancer-related pathways such as inflammation, apoptosis, and cellular proliferation, efforts are required to assess their interaction and impact on current treatment options. Abstract Gastrointestinal cancer (GI) is a global health disease with a huge burden on a patient’s physical and psychological aspects of life and on health care providers. It is associated with multiple disease related challenges which can alter the patient’s quality of life and well-being. GI cancer development is influenced by multiple factors such as diet, infection, environment, and genetics. Although activating immune pathways and components during cancer is critical for the host’s survival, cancerous cells can target those pathways to escape and survive. As the gut microbiome influences the development and function of the immune system, research is conducted to investigate the gut microbiome–immune interactions, the underlying mechanisms, and how they reduce the risk of GI cancer. This review addresses and summarizes the current knowledge on the major immune cells and gut microbiome interactions. Additionally, it highlights the underlying mechanisms of immune dysregulation caused by gut microbiota on four major cancerous pathways, inflammation, cellular proliferation, apoptosis, and metastasis. Overall, gut-immune interactions might be a key to understanding GI cancer development, but further research is needed for more detailed clarification.