12 January - 20 June 2016

Excess zinc can decrease C. difficile resistance

A study led by scientists from Vanderbilt University and published in Nature Medicine suggests that excess dietary zinc can alter gut microbiota and lead to decreased resistance to Clostridium difficile infection.

A study led by scientists from Vanderbilt University and published in Nature Medicine suggests that excess dietary zinc can alter gut microbiota and lead to decreased resistance to Clostridium difficile infection.

Zackular et al. note that C. difficile infections (CDI) have risen greatly in the past 10 years and state that while antibiotic use is the primary risk factor for CDI, non-antibiotic associated cases of CDI are on the increase suggesting other factors may also play a part. They further note that diet can affect gut microbiota and indicate that dietary metals can be associated with risk of infections. Zackular et al. sought to examine the effect of dietary zinc (Zn) on gut microbiota and CDI.

The researchers fed groups of mice either a low Zn diet (0 mg/kg), a control diet (29mg/kg) or high Zn diet (1000mg/kg – approx. 12 times the level of zinc in a standard mouse diet and designed to simulate excess zinc from supplementation in humans) for 5 weeks. Mice fed the high zinc diet showed increased zinc concentrations in cecal and colonic tissue, and faeces.  They also had a decrease in microbial diversity and a change in the microbial community structure compared to the control or low zinc diets.

The researchers also fed the three diets to a mouse model which induced CDI through the administration of an antibiotic, cefoperazone, in their drinking water for five days before being exposed to C. difficile infection. Mice fed the high zinc diet showed “exacerbation” of the CDI compared to the control fed mice but as the overall C. difficile burden was not altered by the different zinc diets, Zackular et al hypothesised that the microbiota changes caused by the zinc might have altered the “threshold of antibiotics needed to confer susceptibility to CDI”.

To test this, the researchers administered a 50 times smaller amount of antibiotic to the mice before infection and found that while the low zinc and control fed mice were not made susceptible to the disease, the high zinc mice were susceptible and showed “severe disease”. They also found that the control diet mice kept their microbial diversity after the antibiotic treatment in contrast to the high zinc fed mice. They state that this suggests that “excess zinc renders the gut microbiota vulnerable to low-level perturbations and decreases the threshold of antibiotics needed to diminish colonisation resistance to C. difficile”.

Zackular et al. also investigated calprotectin, a zinc-binding protein known to have antimicrobial activity. They found that C. difficile culture growth was inhibited by the addition of calprotectin and that calprotectin-deficient mice infected with C. difficile had lower survival and worse disease. Additionally, calprotectin-deficient mice fed a low zinc diet showed “significantly less pathology following infection” indicating, they state, that the mechanisms by which calprotectin protects against CDI are “in part due to the ability to limit zinc during the infection”.

In a press release, one of the researchers, Prof. Skaar, is quoted as saying that “Antibiotics make someone susceptible to C. diff by killing many of the healthy organisms in the gut and decreasing microbial diversity, which allows C. diff to take hold." Skaar added that "A high zinc diet changes the structure of the microbial community in a similar way and reduces the threshold of antibiotics that are needed to convert a resistant microbial community to one that is sensitive to C. diff."

In conclusion, Zackular et al state that their study shows that dietary zinc is important for modulating gut microbiota and that too much zinc lowers the levels of antibiotic required to “confer susceptibility to CDI”. They also note that excess zinc increases the severity of the disease but that calprotectin can help by limiting the availability of zinc in the body and that their findings could help provide future prevention and treatment strategies for CDI.

share this article
RSSL endeavours to check the veracity of news stories cited in this free e-mail bulletin by referring to the primary source, but cannot be held responsible for inaccuracies in the articles so published. RSSL provides links to other World Wide Web sites as a convenience to users, but cannot be held responsible for the content or availability of these sites. This document may be copied and distributed provided the source is cited as RSSL's Food e-News and the information so distributed is not used for profit.

Previous editions

Load more editions

Make an Enquiry