Fecal Flora Transplantation In the Treatment of Colonic and Metabolic Disease

Reference

Grehan MJ, Borody TJ, Leis SM, Campbell J, Mitchell H, Wettstein A. Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol. 2010;44(8):551-561.

Participants

Ten patients undergoing “fecal bacteriotherapy,” or what in the United States is often termed “fecal transplantation.” In this process the bowel is cleansed with antibiotics and then fecal suspensions from healthy donors are administered daily. In this study the first infusion was administered through a colonoscpe and subsequent doses were given over a 60-minute period through a nasal jejunal tube or via enemas. Bowel flora was analyzed at 4, 8, and 24 weeks post-initial infusion and compared with the initial infused donor fecal suspension to determine whether the donor flora had become a stable microbiota of the feces.

Key Findings

At each of the post-infusion intervals in which sample were evaluated, “the bacterial populations in the patients’ fecal samples consisted predominantly of bacteria derived from the healthy donor samples. … 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.”1

Fecal transplantation is not a new. Case reports describing this technique date back at least to the late 1950s. A report by Eiseman el al published in 1958 is credited as the first to describe using fecal enemas, in this case for treatment of pseudomembranous enterocolitis.2

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.

Since that time there have been a number of reports using donor stool delivered both rectally or via nasogastric tubes.3,4,5,6,7,8 Most of these reports focus on treating recalcitrant Clostridium difficile infection.

Two other reports on fecal transplantation were published in the same September issue of the Journal of Clinical Gastroenterology as the Grehan et al study. They are of almost equal significance as Grehan’s study and deserve specific mention.

In one, Yoon et al from Montefiore Medical Center in the Bronx reports on 12 cases of C. difficile successfully treated using donor feces transplanted into the colon through colonoscopy.9 The second paper by Rohlke et al reports on 19 patients again with C. difficile treated with fecal transplantation delivered via colonoscopes. The treatment was successful in all 19 patients treated, and the patients remained disease-free on follow-up of 6 months to 4 years.10

This therapy may be beneficial for treating other types disease besides gastroenteritis.

Borody et al reported striking results in a small trial using fecal transplantation therapy to treat ulcerative colitis (UC) in 2003. They treated 6 patients with “severe, recurrent symptoms and UC had been confirmed on colonoscopy and histology.” Utilizing “retention enemas … repeated daily for 5 days, complete reversal of symptoms was achieved in all patients by 4 months … by which time all other UC medications had been ceased. At 1 to 13 years …, there was no clinical, colonoscopic, or histologic evidence of UC in any patient.”11

Borody is currently recruiting participants for a trial using fecal transplants to treat patients with Parkinson’s disease.12

At a conference in September 2010, Anne Vrieze and colleagues described the results after transplanting fecal flora from lean donors into patients with metabolic syndrome. Their study was a double-blind, randomized, controlled trial. Starting with 18 male subjects with newly diagnosed metabolic syndrome, half received fecal material from lean male donors and half were implanted with their own feces to serve as controls. At the conclusion of the study, fasting triglyceride levels in those subjects who received donor feces were significantly reduced. No effect was seen in the control group re-instilled with their own feces. Peripheral and hepatic insulin sensitivity significantly improved after 6 weeks in the experimental group but not in the control group.13

Current knowledge suggests that the intestinal community of bacterial flora contains at least 1 x 1014 bacteria made up of from 500 to 1,000 different species of anaerobic bacteria.14 Clearly our current methodology of testing these using agar culture media to identify only a handful of species and treating with several limited strains of ‘probiotics’ may be too simple an approach to achieve lasting benefit. Fecal transplantation, although sounding to be primitive, may in fact be a more sophisticated option and have the ability to duplicate a healthy bowel ecosystem in the unwell. As unappealing as it may sound, this may prove to be a useful therapy in coming years.

References

Floch MH. Fecal bacteriotherapy, fecal transplant, and the microbiome. J Clin Gastroenterol. 2010;44(8):529-530.

Eisman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44(5):854-859.

Bowden TA, Mansberger AR, Lykins LE. Pseudomembranous enterocolitis: mechanism of restoring floral homeostasis. Am Surg. 1981;47:178-183.

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.

Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet. 1989;1:1156-1180.

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.

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.

You DM, Franzos MA, Holman RP. Successful treatment of fulminant Clostridium difficile infection with fecal bacteriotherapy. Ann Intern Med. 2008;148:632-633.

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.

Rohlke F, Surawicz CM, Stollman NH. Fecal flora reconstitution for recurrent Clostridium difficile infection: results and methodology. J Clin Gastroenterol. 2010;44:567-570.

Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. 2003;37(1):42-47.

Ananthaswamy A. Faecal transplant eases symptoms of Parkinson’s. New Scientist. 19 Jan 2011.

Vrieze A, et al. Metabolic effects of transplanting gut microbiota from lean donors to subjects with metabolic syndrome. European Association for the Study of Diabetes. EASD 2010; Abstract 90.

Vrieze A, Holleman F, Zoetendal EG, de Vos WM, Hoekstra JB, Nieuwdorp M. The environment within: how gut microbiota may influence metabolism and body composition. Diabetologia. 2010;53(4):606-613.

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