A dysbiotic gut microbiome suppresses antibody-mediated protection against Vibrio cholerae

Abstract Vibrio cholerae is the etiologic agent of cholera, a severe diarrheal disease that represents a significant burden on global health and productivity. Given the need for more effective prophylactics, more research is needed to ascertain the interplay of protective immune responses and the resident gut microbiome, which in cholera-endemic areas is strongly and repeatedly modulated by malnutrition, cholera, and non-cholera infectious diarrhea. Initially, we conducted fecal transplants from healthy human donors into germ-free mice in order to characterize differential immune response activity. As we observed distinctive responses in our initial sampling, we moved to a more tractable antibiotic-treated mouse model where we assemble representative model communities of either human gut microbes resembling those of healthy individuals or those of individuals recovering from diarrhea or malnutrition. We establish these communities in a murine infection model, and show that the dysbiotic gut microbiome, commonly present in areas where malnutrition and diarrhea are common, suppresses the immune response against Vibrio cholerae through the action of CD4+ cells. Our findings suggest that the composition of the gut microbiome at time of infection may be pivotal for providing robust mucosal immunity, suggesting a target for the improvement of responses to oral cholera vaccines.