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

Abstract

Summary Cholera is a severe diarrheal disease that places a significant burden on global health. Cholera’s high morbidity demands effective prophylactic strategies, but oral cholera vaccines exhibit variable efficacy in human populations. One contributor of variance in human populations is the gut microbiome, which in cholera-endemic areas is modulated by malnutrition, cholera, and non-cholera diarrhea. We conducted fecal transplants from healthy human donors and model communities of either human gut microbes that resemble healthy individuals or those of individuals recovering from diarrhea in various mouse models. We show microbiome-specific effects on host antibody responses against Vibrio cholerae , and that dysbiotic human gut microbiomes representative of cholera-endemic areas suppress the immune response against V. cholerae via CD4+ lymphocytes. Our findings suggest that gut microbiome composition at time of infection or vaccination may be pivotal for providing robust mucosal immunity, and suggest a target for improved prophylactic and therapeutic strategies for cholera.

Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels

“…In line with this, several reports have described the influence of the gut microbiome on the immunogenicity of SARS-CoV-2, Rotavirus, Human Papillomavirus, Polio, Tetanus, Pneumococcus and Vibrio cholera vaccines [40][41][42][43][44][45][46][47][48]. Moreover, microbiota dysbiosis caused by antibiotic use has been shown to have detrimental effects on vaccine response [2] and to reduce antibody levels and CD8+ T-cell responses to influenza vaccination [35,49].…”

Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development

“…In addition, it is largely unknown how the microbiota confers resistance or susceptibility to cholera and how it affects the immune response generated by vaccines against this disease (125). In this respect, human microbiota-associated mice could be a valuable animal model to consider (30).…”

“…The start of the seventh cholera pandemic in the 1960s and the spread of this disease throughout Asia and Africa led to increased international interest and funding for cholera research, resulting in the development of the first oral cholera vaccine (OCV). It should be noted that current OCVs exhibit variable PE in human populations for several reasons, including the presence of different V. cholerae strains in endemic areas, immunization coverage, malnutrition, co-infections, and variations in the gut microbiome (29,30). Thus, a cholera vaccine that provides broad and long-lasting protection remains elusive.…”