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

Zackular JP, Moore JL, Jordan AT, Juttukonda LJ, Noto MJ, Nicholson MR, Crews JD, Semler MW, Zhang Y, Ware LB, Washington MK, Chazin WJ, Caprioli RM, Skaar EP
Nat Med. 2016 22 (11): 1330-1334

PMID: 27668938 · PMCID: PMC5101143 · DOI:10.1038/nm.4174

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.

MeSH Terms (33)

Adult Aged Aged, 80 and over Animals Anti-Bacterial Agents Bacterial Proteins Bacterial Toxins Calgranulin B Cecum Child Clostridium difficile Clostridium Infections Cohort Studies Colon Cytokines Diet Disease Models, Animal Disease Susceptibility Enterotoxins Female Gastrointestinal Microbiome Humans Male Mass Spectrometry Mice Mice, Knockout Middle Aged Polymerase Chain Reaction Prospective Studies RNA, Ribosomal, 16S Trace Elements Young Adult Zinc

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