tetano
Editor, Senior Moderator
Cell. 2019 Sep 5;178(6):1313-1328.e13. doi: 10.1016/j.cell.2019.08.010.
[h=1]Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.[/h] Hagan T[SUP]1[/SUP], Cortese M[SUP]1[/SUP], Rouphael N[SUP]2[/SUP], Boudreau C[SUP]3[/SUP], Linde C[SUP]3[/SUP], Maddur MS[SUP]4[/SUP], Das J[SUP]3[/SUP], Wang H[SUP]4[/SUP], Guthmiller J[SUP]5[/SUP], Zheng NY[SUP]5[/SUP], Huang M[SUP]5[/SUP], Uphadhyay AA[SUP]4[/SUP], Gardinassi L[SUP]6[/SUP], Petitdemange C[SUP]4[/SUP], McCullough MP[SUP]2[/SUP], Johnson SJ[SUP]2[/SUP], Gill K[SUP]4[/SUP], Cervasi B[SUP]4[/SUP], Zou J[SUP]7[/SUP], Bretin A[SUP]7[/SUP], Hahn M[SUP]8[/SUP], Gewirtz AT[SUP]7[/SUP], Bosinger SE[SUP]4[/SUP], Wilson PC[SUP]5[/SUP], Li S[SUP]6[/SUP], Alter G[SUP]3[/SUP], Khurana S[SUP]8[/SUP], Golding H[SUP]8[/SUP], Pulendran B[SUP]9[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] 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
[h=1]Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans.[/h] Hagan T[SUP]1[/SUP], Cortese M[SUP]1[/SUP], Rouphael N[SUP]2[/SUP], Boudreau C[SUP]3[/SUP], Linde C[SUP]3[/SUP], Maddur MS[SUP]4[/SUP], Das J[SUP]3[/SUP], Wang H[SUP]4[/SUP], Guthmiller J[SUP]5[/SUP], Zheng NY[SUP]5[/SUP], Huang M[SUP]5[/SUP], Uphadhyay AA[SUP]4[/SUP], Gardinassi L[SUP]6[/SUP], Petitdemange C[SUP]4[/SUP], McCullough MP[SUP]2[/SUP], Johnson SJ[SUP]2[/SUP], Gill K[SUP]4[/SUP], Cervasi B[SUP]4[/SUP], Zou J[SUP]7[/SUP], Bretin A[SUP]7[/SUP], Hahn M[SUP]8[/SUP], Gewirtz AT[SUP]7[/SUP], Bosinger SE[SUP]4[/SUP], Wilson PC[SUP]5[/SUP], Li S[SUP]6[/SUP], Alter G[SUP]3[/SUP], Khurana S[SUP]8[/SUP], Golding H[SUP]8[/SUP], Pulendran B[SUP]9[/SUP].
[h=3]Author information[/h] 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.
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] 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