Journal of Clinical Gastroenterology:
Yale University School of Medicine, Section of Digestive Diseases, New Haven, CT
Reprints: Martin H. Floch, MD, Yale University School of Medicine, Section of Digestive Diseases, 40 Temple Street, Suite 1A, New Haven, CT 06510 (e-mail: firstname.lastname@example.org).
No conflict of interest.
In this issue, there are 3 papers published that involve the fecal microbiome. One is an important physiologic study and 2 are a further elaboration of treatment using fecal bacteriotherapy, now often referred to as fecal transplantation.
In the paper from Australia, Grehan et al1 describe the results of using fecal bacteriotherapy in 10 patients. They classically cleanse the bowel with antibiotics and then infused donor-processed fecal suspensions daily for 5 to 15 days. Their first infusion was done through a colonoscope, but subsequent ones were given over a 60-minute period through a nasal jejunal tube or enemas or a combination of both. They then carefully analyzed the flora at 4, 8, and 24 weeks following the infusions using sophisticated bacteriologic studies. They showed that the donor flora was relatively stable in the microbiota of the feces. This is a landmark study and suggests that the manipulation of the colonic microbiota is effective and holds promise for new therapies in the treatment of colonic or metabolic disease. This study comes after the report recently by Khoruts et al2 who treated Clostridium difficile diarrhea by fecal transplantation and found that 14 days after the transplantation the fecal bacterial flora was similar to that of their donor. As a clear bonus, the C. difficile appeared to be cured. The importance of these reports is that we now can feel comfortable that donor stool microbiota can survive for a significant period of time in the recipient. Therefore, it may be helpful in the treatment of the disease. These papers show its benefit in C. difficile-induced diarrhea.
Fecal bacteriotherapy, now known as fecal transplantation, is not new. From the modern literature, the first case was described by Eiseman et al3 in 1958, and the second description came from Bowden in 1981.4 This was followed by other reports using donor stool in the rectum or through colonoscopy or administered through nasogastric tube.5–8 Most recently, another case has been reported in routine therapy.9 It is now clear that this therapy is successful and is used by experts throughout the country without any adverse effects. These final 2 reports in this issue add strength to its use.10,11 The donor is usually a family member. Obviously, because of the nature of the therapy, it holds certain anxieties for the patient. Nevertheless, its success results in a happy patient. This form of therapy has now reached primetime and should be used in any patient that has been resistant to therapy of recurrent attacks.
The paper from Montefiore Medical Center in the Bronx reports 12 cases that were successfully treated with installation of donor feces into the colon through colonoscopy.10 Although there can be some criticisms of the technique and follow up, it is clear that these 12 patients were benefitted from the treatment.
In the final paper from northern California and the University of Washington, 19 patients were treated with fecal bacteriotherapy delivered through colonoscopes.11 All 19 patients were successfully treated. C. difficile was eradicated in a follow up of 6 months to 4 years.
Although there are still some skeptics, it is clear from all of these reports that fecal bacteriotherapy using donor stool has arrived as a successful therapy. This type of therapy may hold promise in the future to treat other diseases. The group from Australia has attempted its use in inflammatory bowel disease.12
Much more study is needed on this approach, but we must accept that the addition of a normal microbiota to a diseased colon may be helpful in the treatment of colonic disease. Many problems exist in the details of this therapy, as pointed out by Grehan et al1 but, their aggressive leading role in this field is to be commended. Probably one of the major problems is to define how this therapy can become socially accepted. (Can you imagine the Food & Drug Administration discussion?) Nevertheless, replacement of the microflora of an ill person with the microflora from a healthy person holds great promise as a transplant procedure. Metchnikoff13 proposed colectomy in his Noble Prize winning thesis on aging. Can we now propose fecal transplant for disease? Can we change intestinal microecology?14 The report of demonstration of 24-week stability1 of the transplant is historic and adds to the information needed to use fecal transplant as therapy.
1. Grehan MJ, Borody TJ, Leis SM, et al. Durable alternation of the colonic microbiota by administration of donor fecal flora. J Clin Gastroenterol. 2010;44:551–561.
2. Khoruts A, Dicksved J, Jansson JK, et al. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile
-associated diarrhea. J Clin Gastroenterol. 2010;44:354–360.
3. Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44:854–859.
4. Bowden TA, Mansberger AR, Lykins LE. Pseudomembranous enterocolitis: mechanism of restoring floral homeostasis. Am Surg. 1981;47:178–183.
5. Schwan A, Sjölin S, Trottestam U, et al. Relapsing Clostridium difficile
enterocolitis cured by rectal infusion of normal faeces. Scand J Infect Dis. 1984;16:211–215.
6. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile
diarrhoea in six patients. Lancet. 1989;1:1156–1180.
7. Persky SE, Brandt LJ. Treatment of recurrent Clostridium difficile
-associated diarrhea by administration of donated stool directly through a colonoscope. Am J Gastroenterol. 2000;95:3283–3285.
8. Aas J, Gessert CE, Bakken JS. Recurrent Clostridium difficile
colitis: case series involving 18 patients treated with donor stool administered via a nasogastric tube. Clin Infect Dis. 2003;36:580–585.
9. You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile
infection with fecal bacteriotherapy. Ann Intern Med. 2008;148:632–633.
10. Yoon S, Brandt LJ. Treatment of refractory/recurrent C. difficile
-associated disease (CDAD) by donated stool transplanted via colonoscopy: a case series of twelve patients. J Clin Gastroenterol. 2010;44:562–566.
11. Rohlke F, Surawicz CM, Stollman NH. Fecal flora reconstitution for recurrent Clostridium difficile
infection: results and methodology. J Clin Gastroenterol. 2010;44:567–570.
12. Borody TJ, Warren EF, Leis S, et al. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. 2003;37:42–47.
13. Metchnikoff E. The Prolongation of Life. Optimistic Studies. London: Butterworth-Heinemann; 1907.
14. Floch MH. Intestinal microecology. In: Floch MH, Kim AS, eds. Probiotics: A Clinical Guide. Philadelphia: Slack; 2010:3–12.