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Microbiome Food for Thought


Michael Abt and members of his lab in front of an anaerobic chamber where they grow C. diff.

Clostridium difficile, like so many bacteria, are opportunists. Naturally present in many of our guts, these microorganisms sit and wait until the chance arises for them to thrive and wreak havoc. And we’re often the ones to give it to them.

The biggest opening these bacteria take is after antibiotics have been given to a patient to treat other infections. The drugs kill “bad” bacteria, but they also wipe out a lot of the live-in, “good” bacteria, creating the perfect environment for the drug-resistant C. diff strains to make their move. The result is a painful intestinal infection from the bacteria’s toxins that in the United States alone affects nearly half of a million people and causes almost 30,000 deaths each year, according to the U.S. Centers for Disease Control and Prevention.

Diet presents another opportunity for C. diff and other bacteria to cause trouble, researchers continue to find.

“Food is your body’s energy source, but it’s also the food and energy source for the bacteria that live in your gut,” said Michael Abt, PhD, an assistant professor of Microbiology in Penn’s Perelman School of Medicine, who started his lab at Penn in early 2018. “Different types of bacteria thrive with different types of diet, so what you eat shapes the kind of bacteria that live in your gut. And the bacteria in your gut helps determine whether C. diff is pathogenic or not.”

Diets rich in animal protein and saturated fat have been shown to alter the microbiome to the point where the balance of so-called commensal bacteria, such as Bifidobacteria, Firmicutes, and Lactobacillus, dangerously shifts – which has been to linked to inflammatory diseases and obesity. Artificial sweeteners can throw the microbiome out of whack, too. Some “bad” bacteria, including Bacteroides, have the capacity to utilize them as a food source, more so than real sugar, giving them an advantage when the opportunity presents itself.

C. diff, researchers recently discovered, has that same sweet tooth.

A study from earlier this year by a team at Baylor College of Medicine in Houston found a compelling connection between the C. diff epidemic and the addition of a sugar substitute known as trehalose into the food supply. Back around the year 2000, companies in the food industry started switching out table sugar in their products with the substitute because it was cheaper, extended shelf life, and improved food texture. Now everything from ice cream and jam to pasta and ground meat has trehalose.

Roughly three years later, the outbreak of C. diff started.

The Baylor team’s work started a few years before this latest study when they found that the virulent strains of C. diff were more prevalent in the gut than less virulent ones. To figure out why, the researchers analyzed hundreds of different sugars and amino acids to see what the strains preferred. Turns out, two very virulent, drug-resistant strains – known as ribotype 027 and 078 lineages – had a hankering for trehalose and grew exceptionally well on it compared to other strains.

Taking it one step further, they fed trehalose to mice with the strains and found that the infections were worse, and mortality was higher in mice given the food additive.

Trehalose naturally occurs in food, including mushrooms and honey, but at relatively lower amounts compared to what’s in the food supply today.

Abt, a C. diff researcher who wrote a commentary about the findings in a recent issue of the journal Cell Host & Microbe, called the study a “clear, practical example of diet shaping host health via intestinal bacteria.”

“It speaks to the larger idea of how dietary changes shape a person’s gut bacteria, and then how those bacteria shape health and diseases, like obesity, diabetes, and susceptibility to infection diseases,” Abt said.

Indeed, as the microbiome field grows bigger, researchers at Penn Medicine and other institutions keep yielding new insights into the connection between diet and gut health – and ultimately human disease.

“An important contribution of this study is the realization that what we once considered a perfectly safe sugar for human consumption can have unexpected consequences,” the study authors said when the findings published.

Abt said it may be the double whammy that’s fueling the epidemic. The antibiotics used to treat patients create an ideal home for C. diff, and the food additive is the hot meal for them when they arrive. The substitute could be upping the risk for the already high-risk patients, like those in a hospital or nursing home.

This latest research intersects with Abt’s own work. His lab studies the interactions between the host, the immune system, and the microbiome within the context of C. diff infections.

“We’re trying to understand how these three components work together, and specifically, trying to understand how the immune system interacts with the microbiome to either increase severity or ameliorate C. diff disease,” Abt said.

“With this paper, they highlight a fourth component, and it’s diet: What is going on with diet and how is it supporting C. diff growth or potentially inhibit it?” he added. “The research community is looking at C. diff through different lenses to gain a more complete understanding of this disease.”

No need to hit the panic button yet, though, when it comes to food with trehalose. While the study is convincing, it hasn’t been fully investigated in humans, so further research is needed to better understand the C. diff/trehalose relationship and what role it plays in the outbreaks.

Some last food for thought: Ridding food of trehalose wouldn’t necessarily stop infections.

“You would potentially see a decrease in these specific lineages, but I think that other C. diff strains would then bloom and take over,” Abt said. “So if you just take away trehalose but don’t fix the fact that the person’s intestinal microbiome is out of whack and in a state of dysbiosis, another strain of C. diff could take hold.”

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