excess dietary zinc worsens C. diff infection

 Too much dietary zinc increases susceptibility to infection by Clostridium difficile — “C. diff” — the most common cause of hospital-acquired infections.
The findings, reported Sept. 26 in Nature Medicine, call into question the consumption of dietary supplements and cold therapies containing high concentrations of zinc.

It is important to know what you are putting into your body“It is important to know what you are putting into your body,” said Eric Skaar, Ph.D., MPH, professor of Pathology, Microbiology and Immunology at Vanderbilt University. “Multivitamins and other supplements are really only needed by those with a particular nutritional deficit in their diet.”

Skaar and colleagues including Joseph Zackular, Ph.D., discovered that high levels of zinc change the gut’s microbiome — the community of microbial organisms — in a way that mimics antibiotic treatment, the primary risk factor for C. diff infection.
In addition to raising concerns about multivitamin consumption, the findings have particular importance for patients who are hospitalized or taking antibiotics and who are also receiving zinc-supplemented nutrition, which may put them at even greater risk for C. diff infection.
“We need to consider how much zinc these patients have in their diet — and maybe other trace nutrients that might also have an effect on the microbiome,” said Skaar, who is also the Ernest W. Goodpasture Professor of Pathology.
The findings may also partially explain the increasing rates of C. diff infection in people who haven’t been hospitalized or treated with antibiotics, Skaar said. In the United States, C. diff infects about a half million people each year, causing disease ranging from diarrhea to life-threatening inflammation of the colon (colitis), according to the Centers for Disease Control and Prevention.
Skaar and his colleagues used mouse models to explore the impact of dietary metals on susceptibility to infectious diseases.
They demonstrated that mice consuming a high-zinc diet had altered gut microbiota and were susceptible to C. diff infection at lower antibiotic doses compared to mice on a normal zinc diet. Moreover, C. diff caused more severe disease and lethality in mice on a high-zinc diet.
“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 said. “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.”
The investigators also showed that the zinc-binding protein calprotectin is important for combating C. diff by limiting zinc availability during infection.
The findings add to growing evidence that the microbiome is dramatically affected by diet, and suggest that efforts to treat C. diff infections with an “ideal” mix of microbes will be difficult.
Fecal transplants – transfer of stool from a healthy donor to the gastrointestinal tract of a patient with C. diff — have been effective for treating recurrent C. diff colitis, prompting attempts to treat C. diff with a small number of microbes. But the first clinical trial of a “reduced microbial transplant” for C. diff recently failed.
“Everyone’s microbiome is unique, and each microbiome is differentially affected by environmental factors, such as diet,” Skaar said. “There’s a lot we still need to learn about the factors that shape our microbiome, so that we can design successful therapeutic strategies that target this important community of microbes.”
The findings also have implications for the agriculture industry, which uses zinc supplementation to grow bigger animals, Skaar noted.
“It’s possible that zinc supplementation of livestock is leading to animals that are more susceptible to colonization with C. diff, and that might be a way that C. diff is then passed to people,” Skaar said.

A diet containing high levels of zinc may increase the likelihood of developing potentially life-threatening Clostridium difficile infection, particularly among individuals taking antibiotics, a new study finds.

Researchers say individuals at high risk of C. difficile infection should be cautious about using zinc supplements.

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."
Read about a study that describes how deworming drugs could treat C. difficile infection.

Written by Honor Whiteman