Gut Microbiota and Cancer: From Fundamentals to the Research Frontiers

The human gut harbors approximately 40 trillion microorganisms comprising more than 1,000 bacterial species. These microbes play essential roles in maintaining host homeostasis through nutrient metabolism, immune regulation, and defense against pathogens. In recent years, advances in next-generation sequencing technologies have greatly expanded our understanding of the gut microbiota. Dysbiosis, an imbalance in the gut microbial community, has been shown to affect not only intestinal diseases but also diseases of distant organs. Furthermore, accumulating evidence suggests that gut microbiota contributes not only to inflammatory disorders but also to cancer progression. The liver is particularly exposed to gut-derived factors because it receives blood directly from the intestine through the portal vein. Recently, increasing attention has been focused on the relationship between the gut microbiota and liver diseases through “gut–liver axis.” In this lecture, I will provide an overview of the fundamental concepts and recent advances in the field of gut microbiota and cancer. In addition, I will discuss our recent findings on the mechanisms underlying hepatocellular carcinoma progression through the gut–liver axis, with a particular focus on how gut microbiota-derived metabolites and microbial components contribute to the formation of a tumor-promoting microenvironment via senescence-associated secretory phenotype (SASP)-mediated pathways.