Evidence map›Paper›PMID 27668938›Full record

ArticleNature medicine2016

Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection.

Joseph P Zackular, Jessica L Moore, Ashley T Jordan, Lillian J Juttukonda, Michael J Noto, Maribeth R Nicholson, Jonathan D Crews, Matthew W Semler, Yaofang Zhang, Lorraine B Ware and 4 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 169 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 1 pooled it
17.0field-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.

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

169 citing papers in PubMed, 1 synthesis or guideline pooled it, 273 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Acidification-dependent suppression ofInfection and immunity · 2026
    Article
  5. Acidification-dependent suppression ofbioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Dietary iron attenuatesVirulence · 2025
    Article
  10. Review
  11. Review
  12. The emerging view on the roles of butyrate inInfection and immunity · 2025
    Review
  13. Review
  14. Unravelling three-way interactions betweenJournal of medical microbiology · 2025
    Review
  15. Review
  16. Review
  17. Zinc Glycinate Alleviates Necrotic Enteritis Infection in Broiler Chickens.Animals : an open access journal from MDPI · 2025
    Article
  18. Review
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 1 country.

Joseph P ZackularDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jessica L MooreDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Ashley T JordanDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Lillian J JuttukondaDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Michael J NotoDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Maribeth R NicholsonDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Jonathan D CrewsDepartment of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Matthew W SemlerDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Yaofang ZhangDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Lorraine B WareDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
M Kay WashingtonDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Walter J ChazinDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Richard M CaprioliDepartment of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
Eric P SkaarDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vanderbilt University Medical Center · USVanderbilt University · USBaylor College of Medicine · USUnited States Department of Veterans Affairs · US

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
Training (pp 214-245)P41GM103391 · NIGMS · VANDERBILT UNIVERSITY · PI REYZER, MICHELLE L · 2012 to 2020
$17.7M
TRAINING IN GASTROENTEROLOGYT32DK007673 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 1992 to 2026
$8.4M
Host-mediated zinc sequestration during Acinetobacter baumannii infectionR01AI101171 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WALTER J. CHAZIN, DAVID P. GIEDROC · 2013 to 2026
$8.2M
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Clinical and Translational Training Program in Pulmonary MedicineT32HL087738 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Lorraine B Ware · 2007 to 2026
$7.0M
Chemistry-Biology Interface Training GrantT32GM065086 · NIGMS · VANDERBILT UNIVERSITY · PI BACHMANN, BRIAN O, SULIKOWSKI, GARY ALLEN · 2002 to 2022
$7.0M
The impact of dietary metals on the gut microbiome and Clostridium difficile infectionF32AI120553 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI ZACKULAR, JOSEPH PAUL · 2015 to 2017
$109k
Immunotherapeutics for the treatment of Acinetobacter baumannii infectionI01BX002482 · VA · VETERANS HEALTH ADMINISTRATION · PI SKAAR, ERIC P · 2015 to 2017
–
BLRD VA I01 BX002482NHLBI NIH HHS T32 HL087738NIAID NIH HHS F32 AI120553NIAID NIH HHS R01 AI101171NIDDK NIH HHS P30 DK058404NIDDK NIH HHS T32 DK007673NIGMS NIH HHS P41 GM103391NIGMS NIH HHS T32 GM007347NIGMS NIH HHS T32 GM008320NIGMS NIH HHS T32 GM065086
6 · The paper itself

Abstract

Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide. Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically. CDI is most commonly initiated by antibiotic-mediated disruption of the gut microbiota; however, non-antibiotic-associated CDI cases are well documented and on the rise. This suggests that unexplored environmental, nutrient and host factors probably influence CDI. Here we show that excess dietary zinc (Zn) substantially alters the gut microbiota and, in turn, reduces the minimum amount of antibiotics needed to confer susceptibility to CDI. In mice colonized with C. difficile, excess dietary Zn severely exacerbated C. difficile-associated disease by increasing toxin activity and altering the host immune response. In addition, we show that the Zn-binding S100 protein calprotectin has antimicrobial effects against C. difficile and is an essential component of the innate immune response to CDI. Taken together, these data suggest that nutrient Zn levels have a key role in determining susceptibility to CDI and severity of disease, and that calprotectin-mediated metal limitation is an important factor in the host immune response to C. difficile.

Indexed as

AdultAgedAged, 80 and overAnimalsAnti-Bacterial AgentsBacterial ProteinsBacterial ToxinsCalgranulin BCecumChildClostridioides difficileClostridium InfectionsCohort StudiesColonCytokinesDietAnti-Bacterial AgentsBacterial ProteinsBacterial ToxinsCalgranulin BCytokinesEnterotoxinsRNA, Ribosomal, 16SS100A9 protein, mousetcdA protein, Clostridium difficiletoxB protein, Clostridium difficileTrace ElementsZinc

Identifiers

PMID27668938
PMCPMC5101143
OpenAlexW2525178139

What OpenQuestion holds

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LicenceTDM
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.