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

Dietary zinc supplements are in common use, but their effect on infection is unclear. New findings now show that excess dietary zinc reduces the diversity of the gut microbiota and increases the susceptibility of antibiotic-treated mice to Clostridium difficile infection. Clostridium difficile is th...

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Veröffentlicht in:Nature medicine Jg. 22; H. 11; S. 1330 - 1334
Hauptverfasser: Zackular, Joseph P, Moore, Jessica L, Jordan, Ashley T, Juttukonda, Lillian J, Noto, Michael J, Nicholson, Maribeth R, Crews, Jonathan D, Semler, Matthew W, Zhang, Yaofang, Ware, Lorraine B, Washington, M Kay, Chazin, Walter J, Caprioli, Richard M, Skaar, Eric P
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 01.11.2016
Nature Publishing Group
Schlagworte:
101/58
631/326/2565/2134
631/326/2565/855
631/326/421
64/60
692/308/575
692/499
Adult
Aged
Aged, 80 and over
Animals
Anti-Bacterial Agents - pharmacology
Antibiotics
Bacterial Proteins
Bacterial Toxins
Biomedicine
Calgranulin B - genetics
Calgranulin B - metabolism
Cancer Research
Cecum - pathology
Child
Clostridioides difficile
Clostridium difficile
Clostridium infections
Clostridium Infections - metabolism
Clostridium Infections - microbiology
Clostridium Infections - pathology
Cohort Studies
Colon
Colon - pathology
Cytokines - metabolism
Development and progression
Diet
Disease Models, Animal
Disease Susceptibility
Enterotoxins
Female
Gastrointestinal Microbiome - drug effects
Gastrointestinal Microbiome - genetics
Health aspects
Humans
Immune response
Infections
Infectious Diseases
letter
Male
Mass Spectrometry
Metabolic Diseases
Mice
Mice, Knockout
Microbiota
Microbiota (Symbiotic organisms)
Middle Aged
Molecular Medicine
Neurosciences
Nosocomial infection
Nutrients
Pathogens
Pediatrics
Polymerase Chain Reaction
Prospective Studies
Public health
Risk factors
RNA, Ribosomal, 16S - genetics
Scientific imaging
Toxins
Trace Elements - pharmacology
Young Adult
Zinc
Zinc (Nutrient)
Zinc - pharmacology
United States > US
Tennessee
Nashville Tennessee
ISSN:1078-8956, 1546-170X, 1546-170X
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Zusammenfassung:Dietary zinc supplements are in common use, but their effect on infection is unclear. New findings now show that excess dietary zinc reduces the diversity of the gut microbiota and increases the susceptibility of antibiotic-treated mice to Clostridium difficile infection. Clostridium difficile is the most commonly reported nosocomial pathogen in the United States and is an urgent public health concern worldwide 1 . Over the past decade, incidence, severity and costs associated with C. difficile infection (CDI) have increased dramatically 2 . 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 3 , 4 . 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 .
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1078-8956
1546-170X
1546-170X
DOI:10.1038/nm.4174