V. cholerae is a diarrheal disease that affects millions in developing areas annually that lack adequate preventative measures. One possible therapeutic is the use of the gut microbiome, the resident microbial community of the gastrointestinal tract. This community is highly diverse, but how microbial diversity confers resistance or
susceptibility to intestinal pathogens is poorly understood. Using species identified through previous work and transplantation of human microbiomes into several animal models of infection, we show that these species shape the chemical environment of the gut by degrading small molecules used by V. cholerae to activate the expression of virulence genes, leading to reduced pathogen colonization. The absence of these functions and species permits increased infection loads on a personal microbiome-specific basis. These findings suggest new targets for individualized preventative strategies of V. cholerae infection through modulating the structure and function of the gut microbiome.