RePOOPulate: Less sick and less “ick”

Hot off the press this week in the first issue of the open-source journal Microbiome is a paper demonstrating the proof of principle that synthetic stool is an effective alternative for donor stool used in fecal transplants for treating recurrent C. difficile infections. Dr. Emma Allen-Vercoe and her laboratory at the University of Guelph developed the “Robo-gut” to mimic the conditions in the intestine in order to grow a mixture of bacteria cultured from the stool of a healthy donor. They created a  probiotic mixture of diverse microorganisms, which they cleverly termed “rePOOPulate”, that restored regular bowel movement in two patients suffering recurrent C. diff associated diarrhea.

C. difficile is the leading cause of hospital-acquired diarrheal infections in Canada, particularly in the elderly. In recent years NAP1/BI/027 has emerged as a hypervirulent strain that is associated with increased disease severity (Quebec outbreak  2003, Niagara outbreak 2011), posing a continuous threat in the clinical setting. What’s worrying about C. diff infections are the number of individuals that suffer multiple relapsing infections. In these patients it is thought that dysbiosis of the intestinal microbiota prevents re-establishment of a healthy state. That’s where fecal transplants come in, the rationale being to restore the normal microbiota and eradicate infection. The first successful use of fecal transplant in treating C. diff was actually in 1958 (although at the time they were unaware it was a C. diff infection). Since then, over 500 patients have been treated with the achievement of a 95% success rate (see this review for list of published data).

Despite the evidence of success, fecal transplants are a last resort for many patients due to the “ick” factor, and because it is a difficult treatment to regulate. The development of synthetic stool not only removes the unpleasantness of the therapy, but it allows regulation of the bacteria transferred to the patient. The 33 species present in rePOOPulate were grown from healthy stool and screened for antibiotic susceptibility to improve the safety of the treatment.

What remains to be uncovered is the mechanism of how it works. Because the researchers knew what they were putting in they were able to monitor the presence of rePOOPulate bacteria over time in the two patients treated. The percentage of sequences that matched the rePOOPulate bacteria pre-treatment were <7% but between a period of 2 days to 2 weeks post-treatment it increased to 50-70%. After 6 months that proportion decreased to 25-36%. The findings that the recipient microbiome contained signatures of both the individual’s original microbiome and the rePOOPulate bacteria opens exciting new questions of how fecal transplants actually restore the intestinal microbiota to a healthy state that may be applied to other intestinal disorders, such as inflammatory bowel disease.

Naturally the media has fervently picked up the story – probably one of the only times you’ll see “poop” make headlines.