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

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

Author information

1
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
2
Hope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
4
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
5
Department of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
6
Department of Medicine, Emory University, Atlanta, GA 30303, USA.
7
Center for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
8
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
9
Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: bpulend@stanford.edu.

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

PMID:
31491384
DOI:
10.1016/j.cell.2019.08.010

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