Decoding strain level interactions between Vibrio cholerae and gut microbiota

Vibrio cholerae is a highly motile, comma-shaped, Gram-negative bacterium, which can cause severe diarrhea, dehydration, and even human death. Accumulating evidence suggests that gut microbiota and their culture supernatants affect the fitness and colonization of V. cholerae in the host intestine. However, the effects of the most abundant gut bacterial strains on the physiological activities of V. cholerae have not been systematically investigated at the strain level. Here, our systematic screening revealed that gut bacterial culture supernatants exert profound and diverse effects on the physiology of V. cholerae. Specifically, the culture supernatants from Clostridium butyricum L65, Ruminococcus bromii CNGBCC 1800554, and Bacteroides clarus CNGBCC 1801343 strongly inhibited the growth of V. cholerae. In contrast, the culture supernatants of Akkermansia muciniphila L86 and Roseburia inulinivorans DSM 108,070 enhanced the biofilm formation of V. cholerae. Additionally, ROS resistance in Eubacterium rectale CNGBCC 1801156 and R. inulinivorans 108,070 was linked to their KatE activity, while the culture supernatants of Bifidobacterium animalis L73 and R. inulinivorans DSM 108070 significantly suppressed motility. Furthermore, gut microbial culture supernatants modulated the expression of major regulatory genes in V. cholerae. Integration of our data with human cholera cohort data validated Ruminococcus bromii CNGBCC 1800554 as a promising probiotic candidate. This work provides a theoretical foundation and valuable strain resources for further elucidating the interactions between the gut microbiota and V. cholerae at the strain level, and supports the development of next-generation probiotics for cholera prevention and treatment.