Published in the journal Nature Medicine, the study reveals how mice fed a high-zinc diet experienced changes to gut microbiota - the population of microbes in the intestine - and increased susceptibility to C. difficile infection.

C. difficile has emerged as one of the deadliest strains of bacteria in the United States, causing almost half a million infections in 2011 and killing around 29,000 people within 30 days of diagnosis.

The bacterium is shed in feces, and it is most commonly transmitted through contact with contaminated surfaces, such as toilets and bathing tubs.

C. difficile infection is common in healthcare settings; it is primarily transferred to patients through hand contact with medical staff who have touched a surface or object contaminated with the bacterium.

Individuals with prolonged use of antibiotics are known to be at increased risk of C. difficile infection; the drugs can alter gut microbiota, increasing infection susceptibility.

Now, study co-author Eric Skaar, Ph.D., professor of pathology, microbiology, and immunobiology at Vanderbilt University in Nashville, TN, and colleagues suggest high levels of dietary zinc may raise the risk of C. difficile infection in the same way.

Worse C. difficile infection for mice fed a high-zinc diet

According to Skaar and colleagues, previous research has shown that too much dietary zinc - a trace mineral important for a number of bodily functions, including immune system function, cell growth and division, and wound healing - may raise the risk of infectious diseases.

With this in mind, the team set out to determine whether levels of zinc in the diet may influence the risk and severity of C. difficile infection.

To reach their findings, the researchers fed mice either a low-, normal-, or high-zinc diet for 5 weeks; the high-zinc diet was designed to simulate excess dietary zinc in humans, the authors report, with the zinc level around 12 times higher than standard chow.

The effects of these diets on the gut microbiota of the rodents was determined through regular fecal collection and analysis.

Compared with mice fed a low- or normal-zinc diet, those fed a high-zinc diet were found to be more susceptible to C. difficile infection with low doses of antibiotics, and they showed altered gut microbiota.

What is more, mice fed the high-zinc diet experienced more severe and life-threatening C. difficile infection than those fed the low- or normal-zinc diets.

"Based on these findings, our model [shows] that when mice are on a high-zinc diet, this excess zinc restructures the microbiome in a way that enhances susceptibility to C. difficile, enabling increased replication of the organism and increased toxin activity," Skaar told Medical News Today.
Caution urged for zinc supplementation

Skaar said that due to the differences between mice and humans, they are not able to pinpoint the precise level of zinc that raises a person's susceptibility to C. difficile infection.

Still, he told us their results suggest people who are susceptible to C. difficile infection - particularly those using antibiotics - should be cautious about using zinc supplements.

    "We believe our findings indicate that people who are at increased risk for C. difficile should not take zinc supplements unless they have a known zinc deficiency, and in the event that they have a known zinc deficiency the amount supplemented should be carefully dosed so as to avoid excess.

    In addition, we think that these studies show that all people should consider whether a nutritional supplement makes sense for them based on their diet and any known deficiencies. This work demonstrates that blindly supplementing excess nutrients can have severe negative consequences and may tip the balance of host-pathogen interactions in favor of the infecting organism."
    Eric Skaar, Ph.D., Vanderbilt University

In future research, the team hopes to uncover the precise mechanism by which dietary zinc raises susceptibility to C. difficile, which they hope will advance treatments for the infection - such as fecal microbiota transplantation.

"We hope to use this information to increase the efficacy, safety, and generalizability of fecal transplant therapy by learning how dietary metals can affect the microbiome," he told MNT.

"Finally, we are currently expanding this work to determine the impact of alterations in dietary metals on other infectious diseases, and we have some very interesting findings in this regard that we look forward to reporting."