Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans

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Summary

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: (i) Enhanced inflammatory signatures (including AP-1/NR4A expression), observed previously in the elderly, and increased dendritic cell activation; (ii) Divergent metabolic trajectories, with a 1000-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.

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Journal

Journal ID (nlm-journal-id): 0413066

Journal ID (pubmed-jr-id): 2830

Journal ID (nlm-ta): Cell

Journal ID (iso-abbrev): Cell

Title: Cell

ISSN (Print): 0092-8674

ISSN (Electronic): 1097-4172

Publication date Nihms-submitted: 15 August 2019

Publication date (Print): 05 September 2019

Publication date PMC-release: 05 September 2020

Volume: 178

Issue: 6

Pages: 1313-1328.e13

Affiliations

[1 ]Institute for Immunity, Transplantation and Infection, Stanford University 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 ]Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA

[10 ]Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA

[11 ]Present address: Pfizer Inc., Pearl River, NY 10965, USA

[12 ]Present address: School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto - SP 14040, Brazil

[13 ]Present address: HIV Inflammation and Persistence Unit, Institut Pasteur, Paris 75015, France

[14 ]These authors contributed equally

[15 ]Lead Contact

Author notes

[* ]Corresponding author: bpulend@ 123456stanford.edu

Author Contributions

Conceptualization and formulation of original project, B.P. and N.R.; Intellectual contributions throughout project, B.P., N.R., T.H., M.C.; Formal analysis, T.H., M.C., J.D., A.A.U., and L.G.; Investigation, M.C., C.B., C.L., M.S.M., H.W., S.K., J.G., N.Z., M. Huang, C.P., K.G., B.C., J.Z., A.B., and M. Hahn; Visualization, M.C. and T.H.; Validation, C.B., C.L., and G.A.; Writing – Original Draft, T.H., M.C., and B.P.; Writing – Review and Editing, T.H., M.C., and B.P.; Supervision, B.P., N.R., A.T.G., S.E.B., P.C.W., S.K., H.G., S.L., and G.A.; Project Administration, M.C.; Resources, M.P.M., S.J.J., S.K., H.G., S.L., G.A., A.T.G., P.C.W, and S.E.B.; Funding Acquisition, B.P., S.L., S.E.B., and T.H.

Article

Accession ID: PMC6750738 Pmcid ID: PMC6750738 Pmc-uid ID: 6750738 Manuscript ID: nihpa1537108

DOI: 10.1016/j.cell.2019.08.010

PMC ID: 6750738

PubMed ID: 31491384

SO-VID: a60d408e-8bda-4b69-8f74-2737c3bae0ab

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