Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans

Cell. 2019 Sep 5;178(6):1313-1328.e13. doi: 10.1016/j.cell.2019.08.010.

Abstract

Emerging evidence indicates a central role for the microbiome in immunity. However, causal evidence in humans is sparse. Here, we administered broad-spectrum antibiotics to healthy adults prior and subsequent to seasonal influenza vaccination. Despite a 10,000-fold reduction in gut bacterial load and long-lasting diminution in bacterial diversity, antibody responses were not significantly affected. However, in a second trial of subjects with low pre-existing antibody titers, there was significant impairment in H1N1-specific neutralization and binding IgG1 and IgA responses. In addition, in both studies antibiotics treatment resulted in (1) enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (2) divergent metabolic trajectories, with a 1,000-fold reduction in serum secondary bile acids, which was highly correlated with AP-1/NR4A signaling and inflammasome activation. Multi-omics integration revealed significant associations between bacterial species and metabolic phenotypes, highlighting a key role for the microbiome in modulating human immunity.

Keywords: antibodies; bile acids; gene expression profiling; immunology; influenza; metabolomics; microbiota; systems biology; systems vaccinology; vaccines.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Antibodies, Viral / immunology*
  • Antibody Formation
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology*
  • Healthy Volunteers
  • Humans
  • Immunity / drug effects*
  • Immunogenicity, Vaccine / immunology
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology*
  • Male
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Antibodies, Viral
  • Influenza Vaccines