| Literature DB >> 31491384 |
Thomas Hagan1, Mario Cortese1, Nadine Rouphael2, Carolyn Boudreau3, Caitlin Linde3, Mohan S Maddur4, Jishnu Das3, Hong Wang4, Jenna Guthmiller5, Nai-Ying Zheng5, Min Huang5, Amit A Uphadhyay4, Luiz Gardinassi6, Caroline Petitdemange4, Michele Paine McCullough2, Sara Jo Johnson2, Kiran Gill4, Barbara Cervasi4, Jun Zou7, Alexis Bretin7, Megan Hahn8, Andrew T Gewirtz7, Steve E Bosinger4, Patrick C Wilson5, Shuzhao Li6, Galit Alter3, Surender Khurana8, Hana Golding8, Bali Pulendran9.
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.Entities:
Keywords: antibodies; bile acids; gene expression profiling; immunology; influenza; metabolomics; microbiota; systems biology; systems vaccinology; vaccines
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Year: 2019 PMID： 31491384 PMCID： PMC6750738 DOI： 10.1016/j.cell.2019.08.010
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582