Evidence map›Paper›PMID 30890187›Full record

ArticleMicrobiome2019

Species-specific enhancement of enterohemorrhagic E. coli pathogenesis mediated by microbiome metabolites.

Alessio Tovaglieri, Alexandra Sontheimer-Phelps, Annelies Geirnaert, Rachelle Prantil-Baun, Diogo M Camacho, David B Chou, Sasan Jalili-Firoozinezhad, Tomás de Wouters, Magdalena Kasendra, Michael Super and 5 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in Microbiome, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 138 citations in OpenAlex.

  1. Review
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  11. Frontiers in global women's health · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Gastrointestinal tract, its pathophysiology andWorld journal of gastroenterology · 2025
    Review
  16. Review
  17. Review
  18. Article
  19. Microphysiological gut-on-chip enables extendedFrontiers in cellular and infection microbiology · 2025
    Article
  20. Coculture of tumor organoids with pathogenic microorganisms: a novel system to mimicFrontiers in cellular and infection microbiology · 2025
    Review

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

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

15 authors at 3 institutions in 4 countries.

Alessio TovaglieriWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Alexandra Sontheimer-PhelpsWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Annelies GeirnaertDepartment of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Diogo M CamachoWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
David B ChouWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Sasan Jalili-FiroozinezhadWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Tomás de WoutersDepartment of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland.
Magdalena KasendraWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Michael SuperWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Mark J CartwrightWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.
Camilla A RichmondDivision of Gastroenterology, Boston Children's Hospital, Boston, MA, 02115, USA.
David T BreaultDepartment of Pediatrics, Harvard Medical School, Boston, MA, 02115, USA.
Christophe LacroixDepartment of Health Sciences and Technology, ETH Zurich, 8092, Zurich, Switzerland.
Donald E IngberWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA. don.ingber@wyss.harvard.edu.ORCID 0000-0002-4319-6520
Harvard University · USBoston Children's Hospital · USETH Zurich · CH

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAYNE I LENCER · 1986 to 2026
$32.4M
MOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6M
Characterization of Telomerase Expressing Intestinal Stem CellsR01DK084056 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BREAULT, DAVID T · 2010 to 2015
$2.2M
Regulation of Dormant Intestinal Stem CellsK08DK106562 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI RICHMOND, CAMILLA ANN · 2017 to 2019
$496k
NCI NIH HHS T32 CA009216NIDDK NIH HHS K08 DK106562NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK084056
6 · The paper itself

Abstract

backgroundSpecies-specific differences in tolerance to infection are exemplified by the high susceptibility of humans to enterohemorrhagic Escherichia coli (EHEC) infection, whereas mice are relatively resistant to this pathogen. This intrinsic species-specific difference in EHEC infection limits the translation of murine research to human. Furthermore, studying the mechanisms underlying this differential susceptibility is a difficult problem due to complex in vivo interactions between the host, pathogen, and disparate commensal microbial communities.

resultsWe utilize organ-on-a-chip (Organ Chip) microfluidic culture technology to model damage of the human colonic epithelium induced by EHEC infection, and show that epithelial injury is greater when exposed to metabolites derived from the human gut microbiome compared to mouse. Using a multi-omics approach, we discovered four human microbiome metabolites-4-methyl benzoic acid, 3,4-dimethylbenzoic acid, hexanoic acid, and heptanoic acid-that are sufficient to mediate this effect. The active human microbiome metabolites preferentially induce expression of flagellin, a bacterial protein associated with motility of EHEC and increased epithelial injury. Thus, the decreased tolerance to infection observed in humans versus other species may be due in part to the presence of compounds produced by the human intestinal microbiome that actively promote bacterial pathogenicity.

conclusionOrgan-on-chip technology allowed the identification of specific human microbiome metabolites modulating EHEC pathogenesis. These identified metabolites are sufficient to increase susceptibility to EHEC in our human Colon Chip model and they contribute to species-specific tolerance. This work suggests that higher concentrations of these metabolites could be the reason for higher susceptibility to EHEC infection in certain human populations, such as children. Furthermore, this research lays the foundation for therapeutic-modulation of microbe products in order to prevent and treat human bacterial infection.

Indexed as

AnimalsBacteriaBenzoatesCaproatesCells, CulturedEnterohemorrhagic Escherichia coliEscherichia coli InfectionsFemaleGastrointestinal MicrobiomeHeptanoic AcidsHumansIntestinesMaleMiceMicrochip Analytical ProceduresOrgan Culture TechniquesBenzoatesCaproatesHeptanoic Acidshexanoic acid

Identifiers

PMID30890187
PMCPMC6425591
OpenAlexW2907879640

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.