A Common Food Additive Called Trehalose Might Be Responsible for the Clostridium difficile Epidemic

Trehalose, in the food-supply since 2000, may play a role in the increased prevalence and toxicity of Clostridium difficile, according to a new study.

An article appearing in Nature made waves last week when it suggested that a common food additive known as trehalose might be responsible for the current Clostridium difficile epidemic.

Food additives? Infectious diarrhea? This one merits a closer look.

First a bit of background.

These are the infection rates per hospital stay for C. diff over time in the US. You'll note a bit of an uptick starting around the year 2000.

C. diff, like all bacteria, has several strains, and if there's one to worry about it's ribotype 027 – a "hypervirulent" strain that emerged in 1985 but has been outcompeting other C. diff strains over the past 20 years. What gives 027 its competitive edge?

The Nature paper shows us that one thing 027 can do is a bit special – it can metabolize trehalose, a common food additive that the FDA labeled "safe" in the year 2000 – right when 027 starts to really take off.

Trehalose. Think "fun-sized" starch.

So what is trehalose? Chemically, it's two glucose molecules linked by a glucoside bond.

It is the primary blood sugar in flying insects like bees which is of no human interest but is fun to discuss at cocktail parties.

Chock full of trehalose!

Trehalose is not calorie-free and it's a bit sweet but it's mostly a stabilizing agent used in all sorts of processed foods and products – toothpastes, ice cream, breads, hand lotion, gum.

The Nature paper shows us that two of the most virulent strains of C. Diff, including 027, can metabolize even trace amounts of trehalose.  They go on to show that when strains are mixed together, low concentrations of trehalose can lead to natural selection for the 027 strain – it can simply outcompete the less virulent strains by metabolizing this scarce resource.

I asked lead author Dr. Robert Britton about competition with other bacteria.

Dr. Robert Britton

He wrote: “We don’t know about competition with other bacteria but many do have the machinery to eat trehalose (and to actually make it).”

Of course, C. diff usually rises to prominence when other gut bacteria have been killed by antibiotics, meaning competition with other bacteria is limited.

Adding trehalose to the diet of a mouse infected with C. diff is a bad idea.

The paper also suggests that the virulence of the 027 strain may be linked to trehalose directly. When infected mice were given trehalose, they were much more likely to die, as you can see from this Kaplan Meier curve.

Now, this study is not going to lead to a cure for C. diff. If we were to eliminate dietary trehalose I have no doubt that certain strains would evolve to exploit any other energy-containing molecule we put in our bodies. And to be fair, I should mention some studies suggest that trehalose has a protective role in reducing the rate of fatty liver disease.

But this study reminds us that while we may be able to easily determine if a compound is toxic to a human cell, determining how a compound will affect the complex interplay of the human system with the thousands and millions of symbiont species within and around us, is exceedingly difficult. So eat with care.