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Potential Contribution of Dietary Trehalose to C. diff Epidemic

by Lewis Chang, PhD

Clostridium difficile, or “C. diff”, is a bacterium that can cause infection in at-risk individuals, triggering symptoms ranging from mild diarrhea to severe pseudomembranous colitis. Major risk factors for C. diff infection include depletion of protective gut microorganisms due to antibiotics use (e.g. fluoroquinolones), compromised immune system, age, healthcare environment, and certain medications. Hospitalized older individuals with recent antibiotic exposure and those admitted to long-term care facilities are particularly susceptible for C. diff infection.1

Two fluoroquinolone-resistant C. diff ribotypes, RT027 and RT078, have been causing a series of outbreaks since the early 2000s in North America and Europe, respectively, resulting in significant increases in morbidity and mortality. 2 Researchers were alarmed by the rapid spread of these previously rare strains and suspected new factor(s) might have been accountable.

An international collaboration led by researchers from the Department of Molecular Virology and Microbiology at Baylor College of Medicine (Houston, TX) recently discovered that the dietary ingredient trehalose might be an important contributing factor.2 The disaccharide trehalose was granted GRAS (generally recognized as safe) status in 2000 in the US and approved for use in food in Europe in 2001.2 Trehalose can now be found in foods such as ice cream, pasta, and ground beef. The investigators noticed that the widespread use of trehalose in the food industry coincided with the emergence of RT027 and RT078 outbreaks.2

The investigators found in in vitro experiments that trehalose increased the growth of an epidemic strain of RT027 by 5-fold compared with a non-RT027 strain. When testing 21 different C. diff strains, only RT027 and RT078 exhibited enhanced growth on low amounts of trehalose. The subsequent in vivo experiments demonstrated that RT027 strains were able to utilize trehalose and increase the production of disease-causing toxins leading to higher disease severity. Further, in the ileostomy fluid collected from volunteering patients consuming a normal diet, there was a sufficient amount of trehalose to activate RT027.2  With these lines of evidence, the investigators proposed that the use of dietary trehalose as a food additive in the human diet might have fueled the emergence of these drug-resistant C. diff strains. Future human studies are needed to confirm whether severe cases of C. diff infection is associated with increased trehalose in the diet and whether reducing dietary trehalose improves patient outcomes.

Why is this Clinically Relevant?

  • C. diff is the most common infectious cause of antibiotic-associated diarrhea in the US and other developed countries
  • With the increased frequency and severity of C. diff infections globally, prophylactic use of probiotics may be a useful prevention strategy to restore the balance in the gut microbiota, particularly among individuals who undergo antibiotic treatment3-5

View the abstract

References

  1. Burke KE, Lamont JT. Clostridium difficile infection: a worldwide disease. Gut Liver. 2014;8(1):1-6.
  2. Collins J, Robinson C, Danhof H, et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 2018;553(7688):291-294.
  3. Johnston BC, Lytvyn L, Lo CK, et al. Microbial preparations (probiotics) for the prevention of Clostridium difficile infection in adults and children: an individual patient data meta-analysis of 6,851 participants. Infect Control Hosp Epidemiol. 2018:1-11.
  4. Valdes-Varela L, Gueimonde M, Ruas-Madiedo P. Probiotics for prevention and treatment of Clostridium difficile infection. Adv Exp Med Biol. 2018;1050:161-176.
  5. Goldenberg JZ, Yap C, Lytvyn L, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database Syst Rev. 2017;12:CD006095.

 

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