ABSTRACT
Studies in preclinical models support that the gut microbiota play a critical role in the development and progression of colorectal cancer (CRC). Specific microbial species and their corresponding virulence factors or associated small molecules can contribute to CRC development and progression either via direct effects on the neoplastic transformation of epithelial cells or through interactions with the host immune system. Induction of DNA damage, activation of Wnt/ß-catenin and NF-κB proinflammatory pathways, and alteration of the nutrient's availability and the metabolic activity of cancer cells are the main mechanisms by which the microbiota contribute to CRC. Within the tumor microenvironment, the gut microbiota alter the recruitment, activation, and function of various immune cells, such as T cells, macrophages, and dendritic cells. Additionally, the microbiota shape the function and composition of cancer-associated fibroblasts and extracellular matrix components, fashioning an immunosuppressive and pro-tumorigenic niche for CRC. Understanding the complex interplay between gut microbiota and tumorigenesis can provide therapeutic opportunities for the prevention and treatment of CRC.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Gastrointestinal Microbiome , Microbiota , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Colonic Neoplasms/complications , Macrophages , Tumor MicroenvironmentABSTRACT
Dietary patterns and specific dietary components, in concert with the gut microbiota, can jointly shape susceptibility, resistance and therapeutic response to cancer. Which diet-microbial interactions contribute to or mitigate carcinogenesis and how they work are important questions in this growing field. Here we interpret studies of diet-microbial interactions to assess dietary determinants of intestinal colonization by opportunistic and oncogenic bacteria. We explore how diet-induced expansion of specific gut bacteria might drive colonic epithelial tumorigenesis or create immuno-permissive tumour milieus and introduce recent findings that provide insight into these processes. Additionally, we describe available preclinical models that are widely used to study diet, microbiome and cancer interactions. Given the rising clinical interest in dietary modulations in cancer treatment, we highlight promising clinical trials that describe the effects of different dietary alterations on the microbiome and cancer outcomes.