Synthetic stool substitute eradicates refractive C difficile


A stool substitute therapy has promise as an approach to eradication of refractive Clostridium difficile (C difficile) in a proof-of-principle study published January 9 in the inaugural issue of Microbiome.

“We found that, in a small proof-of-principle study, a mixed culture of pure bacteria from a healthy donor given as a probiotic preparation to 2 patients with severe, recurrent C difficile infections was able to clear the infection in both cases, rapidly resolving patient symptoms,” Study co-author Emma Allen-Vercoe, PhD, assistant professor of microbiology, Department of Molecular & Cellular Biology, University of Guelph, Guelph, Ontario, Canada, told Formulary.

The researchers perceived a need to take a highly effective yet crude treatment against C difficile infection-fecal transplantation-and to make it safer, more reproducible, controllable, acceptable, and available. 

“So-called fecal transplantation has a lot of promise as an approach to treatment of refractive C difficile infections, however there are many problems with this method,” Allen-Vercoe said. Using donor stool samples will always carry a risk for infection of patients, despite stringent screening, because there are so many microbial species in stool and we know very little about most of them. Stool is messy to work with and also most of the microbes present in feces are sensitive to oxygen, making the stool transplantation process very time-sensitive.

“And of course, using fecal matter for treatment of disease carries a lot of psychosocial stigma,” Allen-Vercoe added.

The synthetic stool formulation, RePOOPulate, addresses all of these problems, according to Allen-Vercoe.  RePOOPulate has a defined and reproducible content, can be made to order, and has the potential to be produced in enteric-coated, time-release capsule form for oral administration, much like many probiotics on the market. 

“The microbial components of RePOOPulate have been screened to ensure antibiotic sensitivity to allow a level of control over the product,” she said. “And since RePOOPulate does not look-or smell-like stool, it is much more acceptable for patients and their families. Traditional treatment regimens for recurrent C difficile infections include expensive antibiotics that often have to be given over long periods of time.”

RePOOPulate represents a potential 1-application cure for C difficile infection, which will reduce patient morbidity and mortality, as well as reduce hospital costs associated with treatment of patients, implementation of quarantine measures, and increased room cleaning requirements, according to Allen-Vercoe.

In the study, the researchers cultured and characterized the microbes from a supremely healthy donor who had had very minimal prior lifetime exposure to antibiotics.

“From 65 bacterial strains recovered from this donor we selected 33 strains based on their antibiotic sensitivity and lack of species association with disease,” Allen-Vercoe explained. “We prepared a suspension of these RePOOPulate microbes in a saline carrier, and applied this through a colonoscope to the patients.”

“RePOOPulate ‘synthetic stool’ preparation was effective at clearing  C difficile infection both quickly and with only 1 application in both cases,” she said.

Each patient reverted to their normal bowel pattern within 2 to 3 days and remained symptom-free at 6 months.


The most surprising finding was that in both of the patients, despite subsequent courses of antibiotics after RePOOPulate treatment for unrelated infections-1 patient had recurrent urinary tract infections and the other had recurrent soft-tissue infections-neither patient relapsed with C difficile infection, according to ­Allen-Vercoe.

“Thus we believe that the RePOOPulate treatment was successfully able to displace C difficile in both cases after just 1 application,” she said. “We were also able to demonstrate, through next-generation sequencing methods, that the RePOOPulate microbes persisted in the patients’ GI tracts for at least 6 months after treatment. This is fundamentally different from traditional probiotic strains, which are rapidly lost from the body following application, and are unable to persist.”

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