Modulation of the intestinal immune cell compartment by Fusobacterium nucleatum in mice with a minimal complexity microbiota

Colorectal cancer (CRC) is a multifaceted disease, influenced by host genetic and environmental factors. Growing evidence suggests that specific members of the microbiota mediate CRC development, growth and spread. One such microbe is Fusobacterium nucleatum, a normal constituent of the human oral cavity, that has been largely studied for its role in shaping dental biofilms. Fusobacterium spp., while rare in the gut microbiota of healthy individuals, are enriched in human colorectal adenomas and adenocarcinomas, compared to normal colonic tissues, and specifically associated with certain epidemiological subtypes of colorectal cancer. Further experimental evidence has suggested that F. nucleatum can potentiate tumorigenesis in mouse models, influence immune-mediated killing of tumor cells, and promote resistance to chemotherapy drugs. Taken together, this research supports that a greater understanding of the biology underlying F. nucleatum in the gastrointestinal tract—both before and during tumorigenesis—may provide insights into improving CRC diagnosis and treatment. To that end, we seek to understand how F. nucleatum modulates the intestinal immune cell environment. In previous works, F. nucleatum has been shown to influence myeloid cell and T cell frequency in murine and human tumors, respectively. However, we do not yet understand how this oncomicrobe may shape different immune cell populations prior to tumorigenesis, potentially influencing the conversion of healthy intestinal tissue into a pro-tumorigenic microenvironment. As F. nucleatum is a bacterium evolved to live in the oral cavity, we are leveraging gnotobiotic mouse models—in which F. nucleatum can become a stable member of the intestinal microbiota—along with bacterial genetics and immunological approaches to disentangle the interactions at play among F. nucleatum, the colonic epithelium, and the immune system.