The study shows that the sugar – known as trehalose – is metabolised by the potentially deadly bacterium Clostridium difficile.
It suggests the common ingredient has helped trigger epidemics across the world. Trehalose is also used in dried and frozen foods, nutrition bars, fruit fillings, instant noodles and rice and white chocolate. It occurs naturally in small amounts in mushrooms, honey and seafood. In recent years the UK, Europe and the US have seen a sharp increase in hyper-virulent strains that cause severe disease.
Symptoms include diarrhea, fever, loss of appetite, nausea and abdominal pain. But the factors contributing to their emergence have been unclear – until now.
Contributing to hypervirulence
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The study found two genetically distinct C. diff strains that have caused epidemics – known as RT027 and RT078 -have independently acquired unique mechanisms to break down low concentrations of trehalose.
Importantly it also showed this ability to metabolise the sugar was linked with disease severity in mice with a humanised form of C diff. Bacterial strains can be analysed through differences in bits of DNA called ribosomal RNA – and assigned to particular ‘ribotypes’.
Professor Robert Britton and colleagues used whole-genome sequencing and comparative analysis to discover the link. It identifies the C diff strains and the widespread adoption and use of trehalose as a sugar additive in the human diet, and suggest that a harmless food additive may inadvertently select for pathogens.
Prof Britton, of Baylor College of Medicine in Houston, said: “Clostridium difficile disease has recently increased to become a dominant pathogen in North America and Europe, although little is known about what has driven this emergence.
“Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolise low concentrations of the disaccharide trehalose.”
The study, published in the journal Nature, found RT027 strains contain a single mutation in the trehalose that increases its sensitivity to trehalose by more than 500-fold. Prof Britton said: “Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection.”
Meanwhile RT078 strains acquired a cluster of four genes involved in trehalose metabolism. Prof Britton said: “We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.”
Jimmy Ballard, a microbiologist at Oklahoma University who reviewed the study for the journal said it provides a possible explanation for C diff outbreaks since 2001.
He said: “Of particular concern has been the correlation between RT027 and a dramatic increase in deaths related to C. difficile.
“The mystery of why this ribotype and a second one, RT078, became so prevalent apparently out of thin air has remained largely unsolved.”
Ballard said prof Britton’s team “raise the possibility that the seemingly harmless addition of a sugar called trehalose to the food supply contributed to this disease epidemic.”
Mark Wilcox, Professor of Medical Microbiology at Leeds University, said it was “an interesting and well conducted study.”
Dietary changes having unintended consequences
C diff came to prominence in the first decade of this millennium as a cause of life-threatening gut inflammation and diarrhoea, he said.
The ‘live’ part of the study was in mice and it is important to know whether the effects seen are replicated in humans.
Prof Wilcox said: “The association that trehalose can be used by virulent types of C. difficile may be one part of the jigsaw explaining why these became more common.
“However, the association with trehalose does not explain why the more virulent types of C. difficile increased in countries at different times and then were successfully controlled in some of these, as happened for example in the UK over the last 10 years.
“Earlier research has shown that other factors, including the use of particular antibiotics (e.g. fluoroquinolones) that were inactive against virulent types of C. difficile played a key part in their rise to prominence and then their fall.”
Brendan Wren, Professor of Microbial Pathogenesis at the London School of Hygiene & Tropical Medicine, said: “This study provides a good example of how changes in human activity (e.g. changes in food additives) can have unintended consequences relating to the emergence and ultimately the global spread of an infectious agent.” As a food additive trehalose is artificially produced from corn starch using several bacterial enzymes.