Dietary sugar linked to increasing bacterial epidemics

January 3, 2018, Baylor College of Medicine
C. difficile
This photograph depicts Clostridium difficile colonies after 48hrs growth on a blood agar plate; Magnified 4.8X. C. difficile, an anaerobic gram-positive rod, is the most frequently identified cause of antibiotic-associated diarrhea (AAD). It accounts for approximately 15-25% of all episodes of AAD. Credit: CDC

The increasing frequency and severity of healthcare-associated outbreaks caused by bacterium Clostridium difficile have been linked to the widely used food additive trehalose. A team of researchers discovered that in laboratory tests and animal models, trehalose enhances the virulence of epidemic C. difficile lineages that predominate in patient infections. The study appears in the journal Nature.

"C. difficile infections have always been a problem in hospitals, but during the last 15 years they have become the most common cause of hospital-acquired infections in developed countries," said corresponding author Dr. Robert Britton, professor of molecular virology and microbiology and member of the Alkek Center for Metagenomics and Microbiome Research and the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.

According to the Center for Disease Control and Prevention, C. difficile is a major cause of infectious disease-related death in the United States. In 2015, the CDC reported that C. difficile caused almost a half-million infections in patients in a year and 29,000 estimated deaths. The bacteria cause life-threatening inflammation of the colon and diarrhea. Patients 65 years and older are at most risk, and most infections occur in people who have received medical care and antibiotics.

"Our group and others have found that C. difficile lineages RT027 and RT078 have become dominant more recently around the globe," said first author Dr. James Collins, a postdoctoral associate in the Britton lab. "These lineages have been present in people for years without causing major outbreaks; in the 1980s they were not epidemic or hypervirulent but after the year 2000 they began to predominate and cause major outbreaks. We wanted to know what had helped these lineages become a major health risk."

Diet and bacterial virulence

Resistance to fluoroquinolone antibiotics is likely one of the factors that is helping lineage RT027 cause epidemics.

"However, fluoroquinolone resistance is also a characteristic of other C. difficile lineages that are not epidemic," Collins said. "We searched for other factors that would help RT027 and RT078 increase their virulence."

The researchers investigated what sources of food RT027 and RT078 preferred. They discovered that these lineages can grow on levels of sugar trehalose that are about 1,000 times lower than those needed by other lineages of these bacteria, giving RT027 and RT078 a major advantage. Each lineage is highly efficient at using trehalose and evolved independent mechanisms to utilize this sugar. To connect the ability to metabolize low levels of trehalose with increased disease severity, the researchers worked with a mouse model of C. difficile infection.

"Mice received a strain of the RT027 of C. difficile and a diet with or without low trehalose levels," Collins said. "What the mice ate made a difference to the virulence of the infection; mortality was higher in the group consuming trehalose."

Further experiments showed that increased disease severity in the presence of trehalose could not be explained by the mice having higher numbers of bacteria, instead what made the disease more severe was that RT027 produced higher levels of toxins.

These and other experiments provide evidence that dietary trehalose has contributed to the predominance of epidemic C. difficile lineages and to their virulence. Because the genetic factors that allow these bacteria to metabolize trehalose and increase the production of toxins were present well before the outbreaks started, the researchers investigated what could have triggered the epidemics.

"In 2000, trehalose was approved as a food additive in the United States for a number of foods from sushi and vegetables to ice cream, and about three years later the reports of outbreaks with these lineages started to increase," Britton said. "Other factors may also contribute, but we think that trehalose is a key trigger."

"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," Collins said. "Our study suggests that the effect of trehalose in the diet of patients in hospitals with RT027 and RT078 outbreaks should be further investigated."

Explore further: Research opens possibility of reducing risk of gut bacterial infections with next-generation probiotics

More information: J. Collins et al, Dietary trehalose enhances virulence of epidemic Clostridium difficile, Nature (2018). DOI: 10.1038/nature25178

Related Stories

Research opens possibility of reducing risk of gut bacterial infections with next-generation probiotics

August 9, 2017
A team of researchers is exploring the possibility that next-generation probiotics – live bacteria that are good for your health – would reduce the risk of infection with the bacterium Clostridium difficile. In laboratory-grown ...

Multiple strains of C. difficile cause severe patient outcomes

August 20, 2015
No single genetic strain of the widespread Clostridium difficile (C. difficile) bacteria appears to be any more harmful than other strains, according to new research published online today in Infection Control & Hospital ...

Bugs without borders: Researchers track the emergence and global spread of healthcare associated Clostridium difficile

December 9, 2012
Researchers show that the global epidemic of Clostridium difficile 027/NAP1/BI in the early to mid-2000s was caused by the spread of two different but highly related strains of the bacterium rather than one as was previously ...

CDC: in U.S., half million C. difficile infections in 2011

February 26, 2015
(HealthDay)—Almost half a million Americans were infected with the bacteria Clostridium difficile in 2011, and 29,000 died within a month of diagnosis, U.S. health officials say. The report is published in the Feb. 26 issue ...

Type of sugar may treat atherosclerosis, mouse study shows

June 7, 2017
Researchers have long sought ways to harness the body's immune system to treat disease, especially cancer. Now, scientists have found that the immune system may be triggered to treat atherosclerosis and possibly other metabolic ...

Recommended for you

Yeast species used in food industry causes disease in humans

July 19, 2018
A major cause of drug-resistant clinical yeast infections is the same species previously regarded as non-pathogenic and commonly used in the biotechnology and food industries. The study, published on July 19th in the open-access ...

Deadly Rift Valley fever: New insight, and hope for the future

July 19, 2018
Health control measures alone could be ineffective in the long term fight against the deadly Rift Valley fever which affects both humans and animals, a new study in the journal PNAS reports.

New guidelines to diagnose, manage rare endocrine disorders

July 19, 2018
International guidelines have been published for the first time to help doctors around the globe diagnose and manage patients with a very rare set of endocrine diseases known as pseudohypoparathyroidism and its related disorders, ...

Overuse of antibiotics not what the doctor ordered

July 19, 2018
With increased use of antibiotics worldwide linked to growing antibiotic resistance, a world-first study co-authored by a QUT researcher has highlighted the growing impact of non-prescription supply of antibiotics in community ...

Alcohol-related cirrhosis deaths skyrocket in young adults

July 18, 2018
Deaths from cirrhosis rose in all but one state between 1999-2016, with increases seen most often among young adults, a new study shows.

Hidden blood in feces may signal deadly conditions

July 17, 2018
(HealthDay)—Even if it's not visible to the naked eye, blood in the stool can be serious—a sign of a potentially fatal disease other than colon cancer, new research suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.