Abstract

Biofilm formation represents a key survival strategy employed byVibrio choleraeto adapt to the complex intestinal environment of the host. While most previous studies onV. choleraebiofilms have focused on genetic regulation and monospecies cultures, its ability to form dual-species biofilms with other intestinal pathogens is still poorly understood. In this study, using samples from both cholera patients and healthy individuals,Fusobacterium nucleatumwas identified as a bacterium capable of co-aggregating withV. cholerae. Untargeted metabolomic analysis revealed thatF. nucleatum-derived metabolites, specifically 6-hypoxanthine, enhance biofilm formation inV. cholerae. Further validation confirmed that theseF. nucleatum-derived metabolites upregulate the biofilm-associated regulatory genevpsT. In an adult mouse model, co-infection withF. nucleatumandV. choleraesignificantly enhanced the intestinal adaptability ofV. choleraecompared to infection withV. choleraealone. Together, these findings elucidate the mechanism enabling the co-infection ofF. nucleatumandV. choleraein the host intestine, thereby shedding new light on how other pathogenic bacteria can assist inV. choleraeinfection.