Diets high in fat and protein exacerbate C. diff infections in mice

Popular diets low in carbs and high in fat and protein might be good for the waistline, but a new UNLV study shows that just the opposite may help to alleviate the hospital-acquired infection Clostridioides difficile.

In a study published in mSystems, an open access journal of the American Society for Microbiology, UNLV scientists found that an interaction between antibiotic use and a high-fat/high-protein diet exacerbate C. diff infections in mice. Conversely, they found that a high-carbohydrate diet – which was correspondingly low in fat and protein – nearly eliminated symptoms.

C. diff, an intestinal infection designated as an urgent threat by the U.S. Centers for Disease Control and Prevention, is often acquired when antibiotics have wiped out the "good" bacteria in the gut. Hundreds of thousands of people are diagnosed with C. diff infections each year and more than 10,000 die.

Every day, we are learning more about the human microbiome and its importance in human health. The gut microbiome is strongly affected by diet, but the C. diff research community hasn't come to a consensus yet on the effects of diet on its risk or severity. Our study helps address this by testing several diets with very different macronutrient content. That is, the balance of dietary carbohydrate, protein, and fat were very different."

Brian Hedlund, UNLV microbiologist and study co-author

Though studies suggest dietary protein exacerbates C. diff, there's little or no existing research exploring the interaction of a high-fat/high-protein diet with the infection. Hedlund and study co-author Ernesto Abel-Santos, a UNLV biochemist, caution that the study was conducted using an animal model, and more work is underway to begin to establish a link between these diets and infections in people.

"Extreme diets are becoming very popular but we do not know the long-term effects on human health and specifically on the health of the human gut flora," Abel-Santos said. "We have to look at humans to see if it correlates."

Recent studies suggest that because antibiotics kill bacterial species indiscriminately, the medications decimate populations of organisms that compete for amino acids, leaving C. diff free to propagate.

But Hedlund said the story is even more complex. "It's clear that it's not just a numbers game," he said. The new work suggests that diet may promote microbial groups that can be protective, even after antibiotics. For an infection to flourish, he said, "you might need this combination of wiping out C. diff competitors with antibiotics and then a diet that promotes overgrowth and disease."

The new study raised other questions as well. For example: The high-carb diet, which was protective against C. diff infection, gave rise to the least diverse community of microbes.

"Lots of papers say that a lower microbial diversity is always a bad thing, but in this case, it had the best disease outcome," said Abel-Santos. However, he cautions that a high-carb diet could lead to animals becoming asymptomatic carriers that can disseminate the infection to susceptible subjects.

The Abel-Santos lab has been working with C. diff for 12 years with the goal of developing compounds that could prevent infections from this bacterium. The Hedlund lab has been working with C. diff for five years, focusing on the role of diet in infection. This collaboration was supported by a grant from the National Institutes of Health.

Source:
Journal reference:

Mefferd, C.C., et al. (2020) A High-Fat/High-Protein, Atkins-Type Diet Exacerbates Clostridioides (Clostridium) Difficile Infection in Mice, Whereas a High-Carbohydrate Diet Protects. mSystems. doi.org/10.1128/mSystems.00765-19.

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