Rise of C. difficile outbreaks

A common sugar additive in food may fuel deadlier outbreaks of a superbug in hospitals, researchers say.

Clostridium difficile can cause a serious bacterial infection that can rampage through hospitals and lead to severe diarrhea and death. The bowel bug is the most common cause of antibiotic-associated diarrhea.

After 2000, epidemic strains unexpectedly took off in Canada, the United States and Europe and deaths increased dramatically. Why it became so common and severe so quickly had scientists stumped.

This week, American, British and Dutch researchers said they found a new reason to consider: changes in our food supply.

The findings suggest that when the food industry widely adopted the sugar, called trehalose, into food manufacturing, it played a major role in the emergence of super-strong strains of C. difficile.

"Sugar permeates a lot of our diet in ways … we're not really aware of," said Robert Britton, a professor of molecular virology and microbiology at Baylor College of Medicine, who led the study. "Trehalose is a bit of sugar now that the food industry is pretty excited about."

Until now, scientists focused on the toxins that C. difficile produces when people are on antibiotics. The toxins damage the epithelium lining our intestines, Britton said. His team focused on whether the stronger strains of C. difficile outcompetes its cousins. Yes, their series of experiments suggests.

trehalose impacts the physiology of these pathogens inside the intestinal tract.' - Robert Britton

When scientists analyzed the genomes of stronger strains of C. difficile, they found RNA sequences that allowed the bacteria to fuel up on low concentrations of trehalose in a way other strains couldn't.

"Trehalose was able to support growth of ribotype 027 at much lower concentrations than all other garden varieties of C. difficile strains," Britton said.

Table sugar or sucrose is a disaccharide that includes two simpler sugars linked to each other. Trehalose is also a disaccharide. In the food and pharmaceutical industries, trehalose's unique bond offers advantages over other sugars, Britton said.

'Surprising result'

Does trehalose mean there's more bacteria or that they are stronger or more virulent?

"That was the surprising result," Britton told CBC Radio Quirks & Quarks host Bob McDonald. "We thought maybe they would just make the bacteria more abundant in the intestines of mice. But they didn't. It was clear that it was more severe disease and we did see more toxins produced. So there's something more to it about the way that trehalose impacts the physiology of these pathogens inside the intestinal tract."

After manufacturing innovations slashed the cost of trehalose production, food manufacturers applied to regulators like the U.S. Food and Drug Administration, European agencies and Health Canada to use trehalose in food. Regulators agreed.

'Unfortunate perfect storm'

Jimmy Ballard, professor and chair of the department of microbiology and immunology at the University of Oklahoma Health Sciences Center reviewed the study and published a related journal commentary on it.

trehalose as a nutrient source and outcompete other strains. Then, as a result of producing a stronger toxin, the strains make patients sicker. An unfortunate perfect storm.' - Jimmy Ballard

Trehalose seemed to cause one of the strong bacterial strains to produce higher levels of toxin, said Ballard. He studies differences in the toxins that different forms of C. difficile make.

Ballard called the new findings compelling because they fill in the picture of how C. difficile emerged at such high levels when it did. The more toxins are made, the sicker people will be.

"The trehalose models now suggests the strains could have emerged in the human populations due to their ability to use low levels of trehalose as a nutrient source and out compete other strains. Then, as a result of producing a stronger toxin, the strains make patients sicker. An unfortunate perfect storm," Ballard said in an email.

The circumstantial and experimental evidence points to trehalose as an "unexpected culprit" in outbreaks of C. difficile since 2001, Ballard concluded in the journal.

The food manufacturer Cargill successfully applied to Health Canada to add trehalose in the food supply. The company said it is reviewing the new study.

For Ballard, the implications could be more far reaching. As industry introduces new food additives to the food supply, it could influence the microbiome — the teeming populations of microbes in and on us that help and hinder health — in ways that no one can predict, for better or worse, he said.