Fecal bacteriotherapy
Fecal microbiota transplantation (FMT) also known as a stool transplant[1] is the process of transplantation of fecal bacteria from a healthy individual into a recipient[2] as a treatment for patients suffering from Clostridium difficile infection (CDI), which produces effects ranging from diarrhea to pseudomembranous colitis. Beginning in 2000, hypervirulent strains of C. Diff. have emerged, which seem to be linked to antibiotics that are commonly used in empiric treatments.[3] Previous terms for the procedure include fecal bacteriotherapy, fecal transfusion, fecal transplant, stool transplant, fecal enema and human probiotic infusion (HPI). FMT involves restoration of the colonic flora by introducing healthy bacterial flora through infusion of stool, e.g. by enema, obtained from a healthy human donor.
Infusion of feces from healthy donors was demonstrated in a randomized, controlled trial to be highly effective in treating recurrent C. difficile, and more effective than vancomycin alone.[4][5] It can also be used to treat other conditions, including colitis,[6]constipation,[6]irritable bowel syndrome,[6] and some neurological conditions.[7][8]
Description of procedure
The procedure involves single to multiple infusions (e.g. by enema) of bacterial fecal flora originating from a healthy donor. Most patients with CDI recover clinically and have the CDI eradicated after just one treatment.[2][9][10] The procedure can be carried out via enema,[11] through the colonoscope,[12] or through a nasogastric or nasoduodenal tube.[13] Although a close relative is often the easiest donor to obtain and have tested, there is no reason to expect this to affect the success of the procedure as genetic similarities or differences do not appear to play a role;[2] indeed, in some situations a close relative may be an asymptomatic carrier of C.difficile, a disadvantage. Donors must be tested for a wide array of bacterial and parasitic infections.[2] The fecal transplant material is then prepared and administered in a clinical environment to ensure that precautions are taken.[14] The fecal microbiota infusions can be administered via various routes depending on suitability and ease, although enema infusion is perhaps the simplest. There does not appear to be any significant methodological difference in efficacy between the various routes. Repeat stool testing should be performed on patients to confirm eradication of CDI. In over 370 published reports there has been no reported infection transmission.[15]
A modified form of fecal bacteriotherapy (Autologous Restoration of Gastrointestinal Flora - ARGF) that is easier to administer was being developed as of 2009[update].[16] An autologous fecal sample, provided by the patient before medical treatment, is stored in a refrigerator. Should the patient subsequently develop C. difficile, the sample is extracted with saline and filtered. The filtrate is freeze-dried and the resulting solid enclosed in enteric-coated capsules. Administration of the capsules will restore the patient's original colonic flora and combat C. difficile.
Theoretical basis
The hypothesis behind fecal bacteriotherapy rests on the concept of bacterial interference, i.e. using harmless bacteria to displace pathogenic organisms. This approach to combating bacterial infections is not new[17] and has long been used in animals, for example, to prevent salmonellosis in chickens.[18] In the case of CDI, the C.difficile pathogen is identifiable. However in the case of pseudomembranous colitis, whilst C. difficile is the most common cause, there are other C. difficile-negative pseudomembranous colitis cases. In patients with relapsing CDI, the mechanism of action may be the restoration of missing components of the flora including Bacteroidetes and Firmicutes.[19][20][21] The introduction of normal flora results in durable implantation of these components.[22] Another theoretical mechanism entails the production of antimicrobial agents (Bacteriocins) by the introduced colonic flora to eradicate C. difficile. This may be a similar mechanism to that of Vancomycin which originated from soil bacteria, and bacillus thuringiensis which has been proven to produce bacteriocins specific for C. difficile.[23] The potential combination of replacement of missing components and production of antimicrobial products manufactured by the incoming flora are likely to be the mechanisms curing CDI. In the case of ulcerative colitis, no single 'culprit' pathogen has been identified in humans. However since C. difficile colitis responds so well to FMT, it is conceivable that ulcerative colitis may respond in a similar fashion, where the offending infective agent/s are still unknown. It is also possible that an infection persists but cannot be identified as was the case with pseudomembranous colitis when it was first treated in 1958.[11]
Benefits
Benefits of FMT include the restoration of the colonic microbiota to its natural state by replacing missing Bacteroidetes and Firmicutes species, eradication of C. difficile, and resolution of clinical symptoms such as diarrhea, cramping and urgency. Antibiotic resistance in CDI is an uncommon event- rather CDI relapses due to the presence of C. difficile spores.[24]
Although once considered to be "last resort therapy" by some medical professionals due to its unusual nature and 'invasiveness' compared with antibiotics; perceived potential risk of infection transmission; and lack of Medicare coverage for donor stool, the recent position statement by specialists in infectious diseases and other societies[2] is moving away from FMT as a last-resort treatment and toward acceptance of FMT as standard therapy for relapsing CDI and also Medicare coverage in the United States. Dr Martin Floch, the Editor-In-Chief of the Journal of Clinical Gastroenterology, announced in a recent editorial that "FMT using donor stool has arrived as a successful therapy".[25]
Given that antibiotics are the original cause of CDI through their damage of the normal human flora and removal of protective Bacteroidetes and Firmicutes species further antibiotic therapy should be avoided. It has now been recommended that endoscopic Fecal Microbiota Transplantation be elevated to first-line treatment for patients with clinical deterioration and severe relapsing C. difficile infection.[10] The earlier the infusion is initiated, the less likely the patient's condition will deteriorate, thereby preventing the higher mortality rate associated with severely affected patients. Fecal Microbiota Transplantation is being increasingly used in clinical practice and, since complications of FMT are rare, its use is likely to increase.
A 2009 study found that fecal bacteriotherapy has the advantages of being an effective and simple procedure that is more cost-effective than continued antibiotic administration and reduces the incidence of antibiotic resistance.[26]
A randomised study published in the New England Medical Journal in January 2013 reported a 94% cure rate of pseudomembranous colitis caused by Clostridium difficile, by administering fecal microbiota transplant compared to just 31% with vancomycin. The study was stopped prematurely as it was considered unethical not to offer the FMT to all participants of the study due to the outstanding results.[4][27]
As of May 2008[update], studies have also shown that FMT can have a positive effect on neurological diseases such as Parkinson's disease.[8] While Dr. TJ Borody was experimenting with patients that were afflicted by both CDI and Parkinson's disease, he realized that after fecal therapy the symptoms of Parkinson's in his patients began to decrease; some to the point that the Parkinson's could not be detected by other neurologists. The hypothesis for future studies is that the fluctuation in the body's microbiome done by FMT can also be recreated by adding anti-Clostridium difficile antibodies to the patient's body and this technique shall be used in Dr. Borody's future case studies involving Parkinson's disease.[15]
History
The first description of FMT was published in 1958 outlining the successful treatment of four patients with pseudomembranous colitis before C. difficile was the known cause.[11] Since that time sporadic cases have appeared in the literature.
At the CDD there were indications that FMT could benefit other conditions including ulcerative colitis,[28][29]autoimmune disorders,[30] neurological conditions,[7]obesity, metabolic syndrome and diabetes,[15] and Parkinson's disease.[8]
See also
↑Jump back a sectionReferences
- ^ Rowan, Karen (20 October 2012). "'Poop Transplants' May Combat Bacterial Infections". LiveScience.com. Retrieved 2012-10-20.
- ^ a b c d e Bakken, Johan S.; Borody, Thomas; Brandt, Lawrence J.; Brill, Joel V.; Demarco, Daniel C.; Franzos, Marc Alaric; Kelly, Colleen; Khoruts, Alexander; Louie, Thomas; Martinelli, Lawrence P.; Moore, Thomas A.; Russell, George; Surawicz, Christina (1 December 2011). "Treating Clostridium difficile Infection With Fecal Microbiota Transplantation". Clinical Gastroenterology and Hepatology 9 (12): 1044–1049. doi:10.1016/j.cgh.2011.08.014. PMC 3223289. PMID 21871249.
- ^ Gould CV, McDonald LC. Bench-to-bedside review: Clostridium difficile colitis (2008). Crit Care. 12 (1): 203. doi:10.1186/cc6207. PMC 2374604. PMID 18279531 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374604
|PMC=missing title (help). - ^ a b van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ (16 Jan 2013). "Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile". N Engl J Med: 130116140046009. doi:10.1056/NEJMoa1205037. PMID 23323867.
- ^ Grady, Denise (16 January 2013). "When Pills Fail, This, er, Option Provides a Cure". New York Times. Retrieved 2013-01-16.
- ^ a b c Borody, TJ; George, L; Andrews, P; Brandl, S; Noonan, S; Cole, P; Hyland, L; Morgan, A; Maysey, J; Moore-Jones, D (15 May 1989). "Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome?". The Medical journal of Australia 150 (10): 604. PMID 2783214.
- ^ a b Borody TJ, Leis S, Campbell J, et al. (2011). "Fecal Microbiota Transplantation (FMT) in multiple sclerosis (MS)". Am J Gastroenterol 106: S352.
- ^ a b c Ananthaswamy, Anil (19 January 2011). "Faecal transplant eases symptoms of Parkinson's". New Scientist. Retrieved 2013-01-22.
- ^ Kelly CR, De Leon L, Jasutkar N (2012). "Fecal Microbiota Transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results". J Clin Gastroenterol 46 (2): 145–149. doi:10.1097/MCG.0b013e318234570b. PMID 22157239. Unknown parameter
|unused_data=ignored (help) - ^ a b Brandt LJ, Borody TJ, Campbell J. Endoscopic fecal microbiota transplantation: "first-line" treatment for severe clostridium difficile infection? (Sep 2011). "Endoscopic Fecal Microbiota Transplantation". J Clin Gastroenterol 45 (8): 655–657. doi:10.1097/MCG.0b013e3182257d4f. PMID 21716124.
- ^ a b c Eiseman B, Silen W, Bascom GS, et al. (1958). "Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis". Surgery 44 (5): 854–859. PMID 13592638.
- ^ Lund-Tonnesen S, Berstad A, Schreiner A et al. (1998). "Clostridium-difficile-associated diarrhea treated with homologous feces". Tidsskr nor Laegeforen 118 (7): 1027–1030. PMID 9531822.
- ^ Persky SE, Brandt LJ (2000). "Treatment of recurrent Clostridium-difficile-associated diarrhea by administration of donated stool directly through a colonoscope". Am J Gastroenterol 95 (11): 3283–3285. doi:10.1111/j.1572-0241.2000.03302.x. PMID 11095355.
- ^ Borody TJ, Leis S, Pang G et al. Fecal Bacteriotherapy in the treatment of recurrent Clostridium difficile infection. UpToDate
- ^ a b c Borody TJ, Khoruts A (20 Dec 2011). "Fecal microbiota transplantation and emerging applications". Nat Rev Gastroenterol Hepatol 9 (2): 88–96. doi:10.1038/nrgastro.2011.244. PMID 22183182.
- ^ Martin WJ (2009). "Encapsulated Medicines for Iatrogenic Diseases". British Patent Application: GB0916335.3.
- ^ Sanders WE, Sanders C (1984). "Modification of normal flora by antibiotics: effects on individuals and the environment". New Dimensions in Antimicrobial Chemotherapy: 217–241.
- ^ Nurmi E, Rantala M (1973). "New aspects of Salmonella infection in broiler production". Nature 241 (5386): 210–211. doi:10.1038/241210a0. PMID 4700893.
- ^ Chang JY, Antopoulos DA, Kalra A, et al. (2008). "Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea". J Infect Dis 197 (3): 438. doi:10.1086/525047.
- ^ Khoruts A, Dicksved J, Jansson JK, et al. (2010). "Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea". J Clin Gastroenterol 44 (5): 354–360. doi:10.1097/MCG.0b013e3181c87e02. PMID 20048681.
- ^ Tvede M, Rask-Madsen J (1989). "Bacteriohterapy for chronic relapsing clostridium difficile diarrhoea in six patients". Lancet 333 (8648): 1156–1160. doi:10.1016/S0140-6736(89)92749-9.
- ^ Grehan MJ, Borody TJ, Leis SM, et al. (2010). "Durable alteration of the colonic microbiota by the administration of donor fecal flora". J Clin Gastroenterol 44 (8): 551–561. doi:10.1097/MCG.0b013e3181e5d06b. PMID 20716985.
- ^ Rea MC, Dobson A, O'Sullivan O, Crispie F, Fouhy F, Cotter PD, Shanahan F, Kiely B, Hill C, Ross RP (15 Mar 2011). "Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon". Proc Natl Acad Sci U S A 108 (Suppl 1): 4639–4644. doi:10.1073/pnas.1001224107. PMC 3063588. PMID 20616009.
- ^ Best EL, Fawley WN, Parnell P, et al. (2010). "The potential for airborne dispersal of clostridium difficile from symptomatic patients". Clin Infect Dis 50 (11): 1450–1457. doi:10.1086/652648. PMID 20415567.
- ^ Floch MH (2010). "Fecal Bacteriotherapy, Fecal Transplant and the Microbiome". J Clin Gastroenterol 44 (8): 529–530. doi:10.1097/MCG.0b013e3181e1d6e2. PMID 20601895.
- ^ Bakken JS (Dec 2009). "Fecal bacteriotherapy for recurrent Clostridium difficile infection". Anaerobe 15 (6): 285–289. doi:10.1016/j.anaerobe.2009.09.007. PMID 19778623.
- ^ Kelly CP. Fecal Microbiota Transplantation - An Old Therapy Comes of Age (16 Jan 2013). "Fecal Microbiota Transplantation — an Old Therapy Comes of Age". N Engl J Med: 130116140046009. doi:10.1056/NEJMe1214816. PMID 23323865.
- ^ Borody TJ, Warren E, Leis S, et al. (2004). "Bacteriotherapy using fecal flora: Toying with human motions". J Clin Gastroenterol 38 (6): 475–483. doi:10.1097/01.mcg.0000128988.13808.dc. PMID 15220681.
- ^ Borody TJ, Torres M, Campbell J, et al. (2011). "Reversal of inflammatory bowel disease (IBD) with recurrent fecal microbiota transplants (FMT)". Am J Gastroenterol 106: S352.
- ^ Borody TJ, Campbell J, Torres M, et al. (2011). "Reversal of idiopathic thrombocytopenic purpura (ITP) with Fecal Microbiota Transplantation (FMT)". Am J Gastroenterol 106: S352.
External links
- Bacteriotherapy - Development and Delivery of a Treatment for Clostridium difficile
- Video: ABC TV Catalyst, 14 July 2011 - Fecal Bacteriotherapy for Clostridium difficile infection
- Fecal Microbiota Transplant and It's Emerging Medical Applications
- Microbiome talk by Jonathan Eisen on TEDMED 2012
