Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection
Vibrio cholerae causes the diarrheal disease cholera that affects millions of people across the globe and causes over 100,000 deaths yearly. V. cholerae must out-compete the commensal gut microbial community (the gut microbiome) to establish itself in the gut and cause disease. The major functions of normal gut microbiota include nutrient metabolism, nutrient absorption, drug metabolism, and contribute to gut immunomodulation. V. cholerae is a gram-negative bacteria and a major human GI pathogen, despite improvements in treatment and understanding of the mechanisms of pathogenesis, cholera remains a significant global health burden.We describe here that during infection with V. cholerae, individuals with different gut microbiome response differently. We used suckling and adult germfree mice models to introduce different gut communities and examine gut microbiome structure during V. cholerae infection. Next, we showed that the community which includes strains from healthy human is able to decrease cholera infection. Then we identified Vibrio-antagonistic microbes across many different microbiome contexts by setting up combinatorial experiment. Second, we explored how healthy community causes colonization resistance. We showed that this is mediated through the bile salt hydrolase enzyme activity which degrades the bile salt taurocholate that activates the expression of virulence genes. In this dissertation, we used the transplantation of complete human fecal microbiomes and defined communities in both germfree adult mice and suckling antibiotic treated mice models to demonstrate that the variation in gut microbiome can result in different V. cholerae colonization outcomes.