Abstract
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 Vibrio cholerae 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.
Importance Diarrhea caused by enteric bacterial pathogens is a recurring and important issue for worldwide health. Cholera, the severe watery diarrhea caused by the bacterium Vibrio cholerae, affects millions of people annually. Currently, there is a lack of effective preventative measures for cholera, due to the uneven performance of oral cholera vaccines. Thus, it is essential to better understand the factors that may affect vaccine efficacy. One aspect may be variations in the resident community of gut microbes, the gut microbiome, across populations living in developed versus developing regions as a function of host genetics, diet, and infection. Our findings suggest that specific structures of the gut microbiome are involved in disrupting the immune responses to V. cholerae vaccination.
