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

is the etiologic agent of cholera, a severe diarrheal disease that represents a significant burden on global health and productivity. Despite the pressing need, available preventative measures such as oral cholera vaccines exhibit highly variable protective efficacy. We hypothesized that one contributor to vaccine efficacy variability across geographical regions may be due to differences in gut microbiome, which in cholera-endemic areas is strongly and repeatedly modulated by malnutrition, cholera, and non-cholera infectious diarrhea. Here, 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 immunization model, and show that the dysbiotic gut microbiome, commonly present in areas where malnutrition and diarrhea are common, suppresses the immune response against through the action of CD4 cells. Our findings suggest that the composition of the gut microbiome at time of immunization may be pivotal for providing robust immunity from oral cholera vaccines, and highlight the importance of the gut microbiome on mucosal immunization responses and vaccine development strategies.