The human body is inhabited by complex microbial communities, known as the microbiota. While the microbiota usually has beneficial effects on our health, problems can occur when specific species colonize new niches created by diseases such as cancer. A case in point is the recent discovery that the oral commensal Fusobacterium nucleatum promotes colon cancer. Because of the evolutionary distance of F. nucleatum from other bacteria and the lack of genetic tools in the past, little is known about the molecular factors that enable it to colonize the intestinal tract. Many bacteria use specialized metabolites, such as metallophores, toxins or antibiotics, to interact with their host, colonize specific niches, or compete with other members of the microbiota. Our analyses have revealed a significant biosynthetic potential of fusobacteria to produce specialized metabolites, which may influence gut colonization by F. nucleatum. To understand their functional effects on F. nucleatum in the intestinal environment, we will determine their chemical structures and biological activities, identify the physiological signals and molecular factors that regulate their production, and clarify their roles in mediating interactions within the gut microbiome. Our collaborative project combines expertise in natural product research, fusobacterial genetics, infection biology, and intestinal microbiota interactions. Together, we aim to clarify the role of specialized metabolites of fusobacteria in microbial gut communities and to deepen the understanding of fusobacterial gene functions during gut colonization.