Editors' ChoiceMicrobiome

Don’t mix zinc lozenges and antibiotics

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Science Translational Medicine  19 Oct 2016:
Vol. 8, Issue 361, pp. 361ec167
DOI: 10.1126/scitranslmed.aai9159

Clostridium difficile is a leading cause of nosocomial infection, with nearly half a million cases and 29,000 deaths, imposing a significant economic burden on the health system. The incidence and costs associated with C. difficile infection have been increasing over the past decade. A well-accepted risk factor for C. difficile infection is disruption of gut microbial communities following antibiotic use. According to a report from the U.S. Centers for Disease Control and Prevention, there are nearly 154 million antibiotic prescriptions written every year, nearly 30% of which are unnecessary. A majority of these excess antibiotic prescriptions are written for viral upper respiratory infections, such as the common cold, for which individuals are also likely to use zinc-based lozenges. Interestingly, a new study by Zackular et al. has identified high levels of zinc as playing a role in increasing susceptibility to C. difficile infection in a mouse model.

The authors found that giving mice a diet supplemented with zinc decreased microbial diversity and lowered the threshold of antibiotics needed to confer susceptibility to C. difficile infection. Further, the authors showed that calprotectin, a host-derived zinc-binding protein, inhibited growth of C. difficile in culture by decreasing the availability of zinc. This was supported by the increased disease severity and decreased survival of calprotectin-deficient mice following exposure to C. difficile. Whereas calprotectin has been associated with severity of C. difficile infection in human subjects, additional studies are needed to determine its role in zinc-dependent susceptibility to C. difficile.

This study highlights a potential cause for the increasing incidence of C. difficile infection and further brings attention to the need for the judicious use of antibiotics. It also raises concerns regarding the potential interaction of zinc-based lozenges with antibiotics, resulting in disruption of gut microbial communities, thus making gut conditions favorable for pathogen invasion. The tolerable upper limit of zinc intake in humans is 40 mg/day according to the U.S. Department of Health and Human Services, about four times the daily recommended dose, whereas this study examined the effect of supplementing the mouse diet with 12 times the standard dose of zinc for mice. Hence, future studies in human subjects will be needed to determine the validity of these findings at doses encountered in humans. So, don’t throw away the zinc lozenges just yet.

J. P. Zackular et al., Dietary zinc alters the microbiota and decreases resistance to Clostridium difficile infection. Nat. Med. 10.1038/nm.4174 (2016). [Abstract]

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