Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans
Thomas Hagan, Mario Cortese, Nadine Rouphael, Carolyn Boudreau, Caitlin Linde, Mohan S Maddur, Jishnu Das, Hong Wang, Jenna Guthmiller, Nai-Ying Zheng, Min Huang, Amit A Uphadhyay, Luiz Gardinassi, Caroline Petitdemange, Michele Paine McCullough, Sara Jo Johnson, Kiran Gill, Barbara Cervasi, Jun Zou, Alexis Bretin, Megan Hahn, Andrew T Gewirtz, Steve E Bosinger, Patrick C Wilson, Shuzhao Li, Galit Alter, Surender Khurana, Hana Golding, Bali Pulendran, Thomas Hagan, Mario Cortese, Nadine Rouphael, Carolyn Boudreau, Caitlin Linde, Mohan S Maddur, Jishnu Das, Hong Wang, Jenna Guthmiller, Nai-Ying Zheng, Min Huang, Amit A Uphadhyay, Luiz Gardinassi, Caroline Petitdemange, Michele Paine McCullough, Sara Jo Johnson, Kiran Gill, Barbara Cervasi, Jun Zou, Alexis Bretin, Megan Hahn, Andrew T Gewirtz, Steve E Bosinger, Patrick C Wilson, Shuzhao Li, Galit Alter, Surender Khurana, Hana Golding, Bali Pulendran
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.
Conflict of interest statement
Declaration of Interests: Nothing to declare.
Copyright © 2019 Elsevier Inc. All rights reserved.
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Source: PubMed