The Mouse Gut Microbiome is Required for Response to Hepatis B Vaccine

Introduction Gut microbiome as an important impactor is directly linked to the humoral immune system. Whether and how the gut microbiota impacts the response to HBV vaccine remain unknown. We explored the role of gut microbiota on HBsAg-mediated humoral immune response in mice. The metabolites and cellular mechanism were further investigated between gut microbiota and humoral immune response to Hepatitis B vaccine. Methods Juvenile mice were treated with antibiotics and immunized with Hepatitis B vaccine. The plasma hepatitis B surface antibody (HBsAb) IgG level was detected, 16S rDNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) based metabolomics were used to profile the composition of the gut microbiota. Furthermore, antibiotic treated mice were gavaged with the fecal contents of age-matched antibiotic-untreated, or antibiotic-treated mice. The level of HBsAb IgG, IgG1, IgG2a and the B cell subsets such as the plasmablasts, plasma cells and GC B cells in the spleen and blood were analyzed after immunization to profile the B cell response. Results Early-life antibiotic treatment induced an impaired response to the Hepatitis B vaccine, as adult mice exposed to the same dose antibiotics did not have impaired vaccine antibody response. The relative abundance of Firmicutes, Proteobacteria, Antinobacteria and Lactobacillus decreased. Meanwhile, a significantly decreased fecal metabolites were observed with the perturbed gut microbiota, especially compounds vitamins, amino acids, and fatty acids. Antibiotic-treated mice received a fecal microbiota transfer (FMT) from antibiotic-untreated mice showed an increased humoral response, as the plasmablats, plasma cells and GC B cells in the spleen and blood were significantly increased after reconstituting the gut microbiota. Conclusion Early life exposure to antibiotic impaired the humoral immunity response to HBsAg, while the impaired antibody response could be rescued by the FMT. The disturbed gut microbiota with reduced metabolites and the levels of plasmablast, plasma cell and GC B cell changes could be one of the mechanisms of how gut microbiota impacts humoral immunity. However, how the gut microbiota or its metabolites contribute to the impaired humoral immunity remain unknown.