An article in the New England Journal of Medicine, January 2013 explores the validity of faecal transplant therapy for the resolution of C. difficile therapy and reminds us that back in 1958 clinicians in Denver trialled this therapy to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment.[1]
Since then systematic reviews reveals that the reported efficacy of FMT in treating recurrent C. difficile infection is greater than 90%.[2]
So why has this treatment option taken nearly half a century to be taken more and more seriously?
Well the burgeoning field of microbiome research, initially made possible by technologies to identify bacterial 16S ribosomal RNA in complex biologic samples, has developed a far clearer analysis of the abundant, diverse, and influential nature of the gut microbiota.[3] Microbiome research has been expanded and complemented by methods to characterise the protein composition (proteomics) and metabolic processes (metabolomics) of the intestinal contents and those from other body sites.
The results of this study represent a clear precedent in which planned therapeutic manipulation of the human intestinal microbiota can lead to demonstrable, clinically important benefits, thereby bringing faecal transplant therapy to the mainstream of modern, evidence-based medical practice.[4],2,
The mechanism underlying the efficacy of donor-faeces infusion is probably the reestablishment of the normal microbiota as a host defence against C. difficile.[5] Changes in the gut bacterial phyla Firmicutes and Bacteroidetes were associated with C. difficile infection.[6]The researchers found that the faecal microbiota in patients with C. difficile infection had a reduced bacterial diversity, as compared with healthy persons, extending previous observations. [7]Infusion of donor faeces resulted in improvement in the microbial diversity, which persisted over time. Also, there was an increase in Bacteroidetes species and clostridium clusters IV and XIVa (Firmicutes), whereas Proteobacteria species decreased.
In conclusion, in patients with recurrent C. difficile infection, the infusion of donor faeces, as compared with vancomycin therapy, resulted in better treatment outcomes. In particular, patients with multiple relapses of C. difficile infection benefited from this unconventional approach.
Comment
What can we learn from these studies, and how may these translate across other conditions?
- The first is that dysbiosis is an increased risk for persistent infection and that antibiotics are a risk for the development of persistent dysbiosis.
- The second is that restoring a permanent change to bacterial ratios seems possible with faecal transplant – whereas with probiotics this has been elusive
- The implications are that other conditions in which dysbiosis is a causative of amplifying event may respond to faecal transplant therapy
- Lastly, food choice and prebiotics, whilst not discussed also make credible options for manipulation of the ecological mix.
References
[1] van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-415 View Abstract
[2] Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis 2011;53:994-1002 View Full Paper
[3] Shanahan F. The gut microbiota in 2011: translating the microbiota to medicine. Nat Rev Gastroenterol Hepatol 2011;9:72-74 View Abstract
[4] Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958;44:854-859 View Abstract
[5] Khoruts A, Dicksved J, Jansson JK, Sadowsky MJ. Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol 2010;44:354-360 View Abstract
[6] Manges AR, Labbe A, Loo VG, et al. Comparative metagenomic study of alterations to the intestinal microbiota and risk of nosocomial Clostridium difficile-associated disease. J Infect Dis 2010;202:1877-1884 View Abstract
[7] Chang JY, Antonopoulos DA, Kalra A, et al. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis 2008;197:435-438 View Full Paper
1 Comment. Leave new
And there is considerable research on Faecal Transplantion curing Ulcerative colitis…!
This is very recent for CDI
Donor Feces for RecurrentClostridium difficile Infection
A randomized study was halted when feces infusion proved more effective than treatment with vancomycin.
Recurrence of Clostridium difficile infection (CDI) is common, and no effective treatment is available for such episodes. Fecal transplantation has gathered interest as a possible alternative to antibiotics, but experience with it is still limited.
Now, in an open-label, controlled trial involving adults in the Netherlands with recurrent CDI, researchers have examined the efficacy this procedure. Patients were randomized to one of three treatments:
Oral vancomycin for 4 or 5 days, followed by bowel lavage and subsequent infusion of donor feces through a nasoduodenal tube
Oral vancomycin for 14 days (standard therapy)
Oral vancomycin for 14 days with bowel lavage
The primary endpoint was cure (i.e., resolution of CDI-related diarrhea and three consecutive negative stool tests for C. difficile) without relapse within 10 weeks after therapy initiation.
The trial was terminated after an interim analysis. Thirteen (81%) of 16 patients in the infusion group experienced cure after the first infusion, and 2 of the remaining 3 were cured after a second infusion from a different donor. In contrast, only 4 of 13 patients (31%) in the standard-therapy group and 3 of 13 in the vancomycin/lavage group (23%) were cured (P<0.001 for both comparisons with the infusion group). Adverse effects of the infusion were transient and nonsevere.
Comment: The findings of this study will garner much attention and will likely increase the use of fecal transplantation in the treatment of recurrent CDI. These happenings, coupled with our increasing understanding of the gut microbiome, should markedly advance our understanding of the pathogenesis and treatment of CDI.
— Larry M. Baddour, MD
Published in Journal Watch Infectious Diseases January 16, 2013
CITATION(S):
van Nood E et al. Duodenal infusion of donor feces for recurrentClostridium difficile. N Engl J Med 2013 Jan 16; [e-pub ahead of print]. (http://dx.doi.org/10.1056/NEJMoa1205037)