Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection

The gut microbiome is 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 transplantation of human microbiomes into several animal models of infection, we show that key microbiome species shape the chemical environment of the gut through the activity of the enzyme bile salt hydrolase. The activity of this enzyme reduced colonization by the major human diarrheal pathogen Vibrio cholerae by degrading the bile salt taurocholate that activates the expression of virulence genes. 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. [Display omitted] •Interpersonal human gut microbiome variation confers variable infection resistance•Microbiome-dependent infection resistance can be restored through co-transplantation•Colonization resistance is mediated through the bile salt hydrolase enzyme activity•Bile salt hydrolase abundance in human microbiomes correlates to final infection Differences in the gut microbiome between individuals determine resistance to cholera infection through the effects on the activity of a bile salt enzyme.