The Role of the Gut Microbiome in Shaping Immune Responses to Vibrio cholerae

Vibrio cholerae is the etiologic agent of cholera, a severe diarrheal disease that represents a significant burden on global health and productivity. The high morbidity of cholera demands effective prophylactic strategies, but oral cholera vaccines exhibit variable immunogenicity and efficacy in human populations. One variable factor in human populations is the gut microbiome, the resident community of microorganisms in the gut, which in cholera-endemic areas is strongly and repeatedly modulated by malnutrition, cholera, and non-cholera diarrhea. However, the role of microbiome variations in immune responses against V. cholerae and oral cholera vaccination is not well understood. We conducted fecal transplants from healthy human donors and model communities of either human gut microbes resembling those of healthy individuals or those of individuals recovering from diarrhea or malnutrition in various mouse models. We show microbiome-specific effects on host antibody responses against V. cholerae, and that dysbiotic human gut microbiomes, commonly present in areas where malnutrition and diarrhea are common, suppresses the immune response against V. cholerae through the action of CD4+ lymphocytes. Our findings suggest that the composition of the gut microbiome at time of infection or vaccination may be pivotal for providing robust mucosal immunity, suggesting a target for the improvement of prophylactic and therapeutic strategies for cholera