Evidence map›Paper›PMID 31491384›Full record

Trial reportCell2019

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 and 19 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04884776 (Modulation of Gut Microbiota to Enhance Health and Immunity of Vulnerable Individuals During COVID-19 Pandemic), which is not on this map. Cited by 385 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
385citing papers in PubMed, 2 pooled it
27.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04884776 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Modulation of Gut Microbiota to Enhance Health and Immunity of Vulnerable Individuals During COVID-19 Pandemic

TypeinterventionalSponsorChinese University of Hong KongRan2021 to 2024Enrolled453ConditionsGut Microbiota, COVID-19 VaccineArmsMicrobiome immunity formula, Active placebo
3 · Its place in the literature

Who cites it

385 citing papers in PubMed, 2 syntheses or guidelines pooled it, 570 citations in OpenAlex.

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325 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 1 country.

Thomas HaganInstitute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Mario CorteseInstitute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Nadine RouphaelHope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
Carolyn BoudreauRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Caitlin LindeRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Mohan S MaddurEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Jishnu DasRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Hong WangEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Jenna GuthmillerDepartment of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
Nai-Ying ZhengDepartment of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
Min HuangDepartment of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
Amit A UphadhyayEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Luiz GardinassiDepartment of Medicine, Emory University, Atlanta, GA 30303, USA.
Caroline PetitdemangeEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Michele Paine McCulloughHope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
Sara Jo JohnsonHope Clinic of the Emory Vaccine Center, Decatur, GA 30030, USA.
Kiran GillEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Barbara CervasiEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Jun ZouCenter for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Alexis BretinCenter for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Megan HahnDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Andrew T GewirtzCenter for Inflammation, Immunity, and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
Steve E BosingerEmory Vaccine Center, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Patrick C WilsonDepartment of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA.
Shuzhao LiDepartment of Medicine, Emory University, Atlanta, GA 30303, USA.
Galit AlterRagon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
Surender KhuranaDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Hana GoldingDivision of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
Bali PulendranInstitute 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.
Emory National Primate Research CenterRagon Institute of MGH, MIT and Harvard · USUniversity of Chicago · USCenter for Biologics Evaluation and Research · USGeorgia State University · USStanford University · USEmory and Henry College · USEmory University · USHOPE Clinic · US

Funding

Yerkes National Primate Research Center Role of type-I IFN in regulating COVID-19 induced inflammation and pathogenesisP51OD011132 · OD · EMORY UNIVERSITY · PI Joon Sup Lee · 2012 to 2026
$167.0M
VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGEDU19AI057266 · NIAID · EMORY UNIVERSITY · PI Rafi Ahmed · 2003 to 2026
$81.7M
Systems Biological Analysis of Innate and Adaptive Responses to VaccinationU19AI090023 · NIAID · EMORY UNIVERSITY · PI AHMED, RAFI, LI, SHUZHAO · 2010 to 2021
$45.0M
MOLECULAR &CELLULAR IMMUNOBIOLOGYT32AI007290 · NIAID · STANFORD UNIVERSITY · PI Sean Curtis Bendall, Olivia M Martinez · 1985 to 2026
$27.0M
Toward a Universal Influenza Virus VaccineP01AI097092 · NIAID · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI PALESE, PETER · 2012 to 2022
$17.6M
Simultaneous antigen receptor repertoire profiling and single-cell transcriptomics in T and B lymphocytes from limited clinical samplesU24AI120134 · NIAID · EMORY UNIVERSITY · PI BOSINGER, STEVEN EDWARD · 2015 to 2024
$6.5M
MICROBES, DENDRITIC CELL SUBSETS AND T-CELL IMMUNITYR01AI048638 · NIAID · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2001 to 2024
$4.5M
Understanding the Role of Mucosal Antigen Presenting Cells in Regulating Immune ResponseR37AI048638 · NIAID · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2009 to 2018
$4.0M
Polarizing T Cell Responses in vivo With Dendritic CellsR37DK057665 · NIDDK · STANFORD UNIVERSITY · PI PULENDRAN, BALI · 2010 to 2019
$3.9M
Multiscale, multifactorial immune networks as a web serviceUH2AI132345 · NIAID · EMORY UNIVERSITY · PI LI, SHUZHAO · 2017 to 2018
$423k
NIAID NIH HHS HHSN272201400004CNIAID NIH HHS P01 AI097092NIAID NIH HHS R01 AI048638NIAID NIH HHS R37 AI048638NIAID NIH HHS T32 AI007290NIAID NIH HHS U19 AI057266NIAID NIH HHS U19 AI090023NIAID NIH HHS U24 AI120134NIAID NIH HHS UH2 AI132345NIDDK NIH HHS R37 DK057665NIH HHS P51 OD011132
6 · The paper itself

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.

Indexed as

AdolescentAdultAnti-Bacterial AgentsAntibodies, ViralAntibody FormationFemaleGastrointestinal MicrobiomeHealthy VolunteersHumansImmunityImmunogenicity, VaccineInfluenza A Virus, H1N1 SubtypeInfluenza, HumanInfluenza VaccinesMaleYoung AdultAnti-Bacterial AgentsAntibodies, ViralInfluenza Vaccinesantibodiesbile acidsgene expression profilingimmunologyinfluenzametabolomicsmicrobiotasystems biologysystems vaccinologyvaccines

Identifiers

PMID31491384
PMCPMC6750738
OpenAlexW2971999614

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.