Dietary Zinc Alters the Microbiota and Decreases Resistance to Clostridium difficile Infection

Autor: Yaofang Zhang, Michael J. Noto, Richard M. Caprioli, Ashley T Jordan, Matthew W. Semler, Jessica L. Moore, Jonathan D. Crews, Walter J. Chazin, Lillian J. Juttukonda, Maribeth R Nicholson, Lorraine B. Ware, M. Kay Washington, Eric P. Skaar, Joseph P. Zackular
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
genetic structures
Antibiotics
Gut flora
Polymerase Chain Reaction
Mass Spectrometry
Cohort Studies
Enterotoxins
Mice
RNA
Ribosomal
16S
Prospective Studies
Child
Cecum
Aged
80 and over
Mice
Knockout
biology
General Medicine
Middle Aged
Clostridium difficile
Antimicrobial
Anti-Bacterial Agents
3. Good health
Zinc
Cytokines
Female
Disease Susceptibility
Adult
Colon
medicine.drug_class
Bacterial Toxins
General Biochemistry
Genetics and Molecular Biology
Article
Microbiology
Young Adult
03 medical and health sciences
Immune system
Bacterial Proteins
medicine
Animals
Calgranulin B
Humans
Microbiome
Aged
Innate immune system
Clostridioides difficile
biology.organism_classification
Diet
Gastrointestinal Microbiome
Trace Elements
Disease Models
Animal
030104 developmental biology
Immunology
Clostridium Infections
Calprotectin
Zdroj: Nature medicine
ISSN: 1546-170X
1078-8956
Popis: 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.
Databáze: OpenAIRE
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