Evidence map›Paper›PMID 34551799›Full record

ArticleGenome biology2021

The influence of the gut microbiome on BCG-induced trained immunity.

Martin Stražar, Vera P Mourits, Valerie A C M Koeken, L Charlotte J de Bree, Simone J C F M Moorlag, Leo A B Joosten, Reinout van Crevel, Hera Vlamakis, Mihai G Netea, Ramnik J Xavier

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 8% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Upper respiratory tract commensalJournal of thoracic disease · 2026
    Article
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  4. Article
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  7. Article
  8. Female-enrichedbioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Article
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  18. Pathophysiology and genomics of bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2024
    Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 5 countries.

Martin Stražar *Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vera P Mourits *Department of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Valerie A C M KoekenDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
L Charlotte J de BreeDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Simone J C F M MoorlagDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Leo A B JoostenDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Reinout van CrevelDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
Hera VlamakisBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Mihai G NeteaDepartment of Internal Medicine, Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands. mihai.netea@radboudumc.nl.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA, USA. xavier@molbio.mgh.harvard.edu.ORCID 0000-0002-5630-5167
Radboud University Nijmegen · NLBroad Institute · USStatens Serum Institut · DKUniversity of Bonn · DE

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
NIDDK NIH HHS P30 DK043351NIH HHS P30 DK043351
6 · The paper itself

Abstract

backgroundThe bacillus Calmette-Guérin (BCG) vaccine protects against tuberculosis and heterologous infections but elicits high inter-individual variation in specific and nonspecific, or trained, immune responses. While the gut microbiome is increasingly recognized as an important modulator of vaccine responses and immunity in general, its potential role in BCG-induced protection is largely unknown.

resultsStool and blood were collected from 321 healthy adults before BCG vaccination, followed by blood sampling after 2 weeks and 3 months. Metagenomics based on de novo genome assembly reveals 43 immunomodulatory taxa. The nonspecific, trained immune response is detected by altered production of cytokines IL-6, IL-1β, and TNF-α upon ex vivo blood restimulation with Staphylococcus aureus and negatively correlates with abundance of Roseburia. The specific response, measured by IFN-γ production upon Mycobacterium tuberculosis stimulation, is associated positively with Ruminococcus and Eggerthella lenta. The identified immunomodulatory taxa also have the strongest effects on circulating metabolites, with Roseburia affecting phenylalanine metabolism. This is corroborated by abundances of relevant enzymes, suggesting alternate phenylalanine metabolism modules are activated in a Roseburia species-dependent manner.

conclusionsVariability in cytokine production after BCG vaccination is associated with the abundance of microbial genomes, which in turn affect or produce metabolites in circulation. Roseburia is found to alter both trained immune responses and phenylalanine metabolism, revealing microbes and microbial products that may alter BCG-induced immunity. Together, our findings contribute to the understanding of specific and trained immune responses after BCG vaccination.

Indexed as

AdolescentAdultAgedBacillotaBCG VaccineCohort StudiesCytokinesFemaleGastrointestinal MicrobiomeHumansMaleMetagenomicsMiddle AgedPhenylalanineYoung AdultBCG VaccineCytokinesPhenylalanineBCGEggerthella lentaMicrobiomeNonspecific immune responsesPhenylalanine metabolismRoseburiaTrained immunity

Identifiers

PMID34551799
PMCPMC8456614
OpenAlexW3199981146

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.