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Nat Med. 2016 Nov;22(11):1330-1334. doi: 10.1038/nm.4174. Epub 2016 Sep 26.

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

Author information

1
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
2
Department of Chemistry, Vanderbilt University, Nashville, Tennessee, USA.
3
Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee, USA.
4
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
5
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
6
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
7
Department of Biochemistry, Vanderbilt University, Nashville, Tennessee, USA.
8
Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, USA.
9
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
10
Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, Tennessee, USA.

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.

PMID:
27668938
PMCID:
PMC5101143
DOI:
10.1038/nm.4174
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing financial interest.

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