New Approach Offers Improved Outcomes Over Stool Transplant in Patients with C. difficile Infection

According to a news release from the University of Guelph, scientists at the university have developed a synthetic form of feces that “can cure nasty gastrointestinal infections caused by Clostridium difficile” (C. difficile).

The synthetic stool (dubbed “RePOOPulate” by its creators) is a super-probiotic grown from purified intestinal bacterial cultures in a machine that “mimics the environment of the large intestine.”

The news release notes that “Besides offering an effective therapy against the deadly superbug, the artificial poop is safer, more stable and adaptable, and less ‘icky’ than treatments for C. difficile infection such as fecal bacteriotherapy.”

In an article titled “Stool Substitute Transplant Therapy for the Eradication of Clostridium difficile Infection: ‘RePOOPulating’ the Gut,” published in the journal Microbiome, the authors noted that “few effective treatments exist” for patients with recurrent Clostridium difficile infection. One treatment, fecal bacteriotherapy (“stool transplant”), has “has shown promising results in preliminary studies.” However, the procedure is also associated with several challenges, including “pathogen transmission, patient acceptance and inability to standardize the treatment regimen.”

The authors tested RePOOPulate in two patients with recurrent C. difficile infection who had not responded to standard treatment. For the study, the synthetic stool used in treatment was “developed by extensively culturing the microbial diversity” from the stool of a healthy donor. In all, 33 bacterial isolates, “representing commensal species that were generally sensitive to a range of antimicrobials and were relatively straightforward to culture,” were selected for the final stool substitute formulation.

The patients were taken off of antiobiotic therapy for two days prior to the start of treatment, and underwent standard colon cleansing the night before. During the procedure the next day (performed via colonoscopy), physicians deposited half of the treatment solution “in the region of the cecum/proximal ascending colon and the other half was drizzled throughout the transverse colon as the colonoscope was withdrawn.” Patients were advised to eat a fiber-rich diet and to refrain from consuming products containing probiotics.

In one patient, researchers detected no C. difficile at 10 days post-procedure. The patient received “several courses of antibiotics for recurrent urinary tract infections in the subsequent weeks following her stool substitute treatment, but her diarrhea did not recur. She remained symptom-free at the last evaluation, 24 weeks after treatment.”

The other patient in this study was symptom-free for three weeks following treatment. She developed recurrent cellulitis and “was placed on ceftriaxone by her physician. She was monitored closely while on ceftriaxone but did not develop loose stool or diarrhea. She suffered from several skin and soft tissue infections in the subsequent weeks and received several additional courses of broad-spectrum antibiotics for these infections. Nevertheless, she remained symptom-free with no diarrhea at last evaluation, which was 26 weeks post procedure.”

In their discussion of these results, the authors wrote that this study “shows that a synthetic stool (stool substitute) may be an effective and feasible alternative to the use of defecated donor fecal matter (stool transplant)” in the treatment of recurrent C. difficile infection. They noted that the use of synthetic stool has several advantages over the conventional approach to stool transplant, including:

• The exact composition of bacteria administered is known and can be controlled
• The bacterial species composition can be reproduced, should a future treatment be necessary
• Preparations of pure culture are more stable than stool
• An absence of viruses and other pathogens in the administered mixture can be ensured, thereby improving patient safety
• The administered organisms can be selected based on their sensitivity to antimicrobials, allowing an enhanced safety profile

The authors concluded that although further study of synthetic stool is needed, given the limited treatment options available to patients who fail vancomycin therapy, an approach that uses “Ecosystem therapeutics or repopulating the bowel with defined communities of normal intestinal bacteria offers another effective therapy” for treating recurrent C. difficile infection.

Some researchers have speculated that fecal transfer may hold promise for the treatment of several other gastrointestinal conditions, including inflammatory bowel disease, irritable bowel syndrome, and severe ulcerative colitis. There is also the possibility that “it may prove a treatment for obesity, given the differing populations of intestinal bacteria in the bowels of obese humans and animals compared to the nonobese.”