Sunday, January 20, 2013

Fecal transplants and IBD

Brother can I borrow some feces?



IBD is often linked to abnormal gut flora – the presence of “bad” bacteria, the absence of “good” bacteria, or an unhealthy bacterial cocktail are potentially associated with Crohns and Ulcerative Colitis.  Those with IBD have fewer bacteria in their intestines overall, and Clostridium coccoides, Clostridium Leptum and Lactobacillus are less prevalent.  Other bacterial species appear to be more prevalent, including Bacteroides vulgatus and certain E. Coli strains.  While none of this proves that bacterial abnormalities cause IBD, there is a correlation. (1,2)

Fecal microbiota transplantation (FMT), more commonly known as fecal transplants.  FMT is receiving a lot of recent press, but it has been around since the 1950’s.  FMT involves finding a healthy donor, who has their feces removed and made into a slurry for transplantation.  The donor can be a close relative, though for genetically predisposed conditions often a non-relative is chosen.  The slurry is then delivered to the bowels of the patient – generally through either enema or nasogastric tube.  Current research is looking into capsule-based delivery, and the storage of an individual’s own feces prior to antibiotic treatment to repopulate the gut and “reboot” following the wipeout of the resident species by the antibiotics.

Nothing sounds more like snake oil than a tube snaked through your nose into your gut that is injected with poo, but there is a sound medical basis for the treatment.  When a bacterial infection of the intestines occurs, the offending bacteria generally displaces the helpful (or benign) bacteria.  Once a more amenable species takes over again, the symptoms abate.  FMT seeks to speed up this process by the introduction of helpful bacteria.  This has been studied as a potential treatment for IBD since at least 1989. (3)

Before looking at the efficacy of FMT for IBD, let’s look at the better studied applications.  Perhaps the best studied (and most recent headline grabbing) application is the use in treating Clostridium Difficile (or C. Diff) infections.  C. Diff is notoriously difficult to treat using antibiotics, frequently causes diarrhea, and has been known to recur when not fully addressed.  Standard antibiotic treatments generally result in a temporary increase in diarrhea, which can necessitate additional treatment to replenish fluids and prevent dehydration.  Alternative treatments have shown promise (http://evidencebasedibd.blogspot.com/2012/11/probiotics.html), but the dance card is still open for better ways to address the issue.

FMT has been studied on numerous occasions as a treatment for C. Diff infection.  Overall, the results are impressive – 87% of individuals had successful outcomes with FMT treatment, with minimal adverse side effects.  The results show a better response than typical antibiotic treatment on both fulminant and refractory C. Diff infections.  While the results come from multiple studies and are impressive, there haven’t been any large scale studies and none of the current studies were double blinded.  Given the diversity of the studies, however, FMT has at least been proven to have very strong preliminary evidence of being effective, and should be a consideration for those with difficult to treat C. Diff infections.(4)  There appear to be no major differences in methods of administration – either nasogastric (or nasojejunal), by colonoscopic implantation, or via enema.  In one small scale study, even home administration by enema from a donor that was mixed in a blender had positive results (though I would question the reuse of the same blender for milkshakes later that evening). (5)

What about Crohn’s Disease and Ulcerative Colitis with FMT?  A recent study in Gastroenterologie showed minimal effect on severe Ulcerative Colitis (there was a small initial effect, but a 12 week followup showed no statistically significant difference) (6).  A similar, small study with Crohn’s disease patients showed little impact 8 weeks after treatment, with mixed short-term effect and some minor adverse reactions (fever, diarrhea).  (7)  The only large review study likewise showed mixed results – some self-reporting and small studies showed promise, but over seventeen articles there were only 41 patients that met the inclusion criteria, and several of those has C. Diff infections.  As such, there is no good clinical evidence to support the use of FMT in treating IBD, however the matter has not been fully studied and because of the efficacy with C. Diff and the sound theory behind it, there is ample opportunity for larger scale, controlled studies to evaluate the technique. 

Bottom Line


·         Fecal transplants are a viable treatment for C. Diff.  The mechanism of delivery is largely irrelevant, and adverse results are minimal.
·         FMT has not been statistically shown to be effective in IBD, but the data is limited and larger trials are underway.
·         FMT studies should be monitored over the next couple of years to see if better studies show efficacy. 

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1.       SEKSIK, P., SOKOL, H., LEPAGE, P., VASQUEZ, N., MANICHANH, C., MANGIN, I., POCHART, P., DORÉ, J. and MARTEAU, P. Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease.  Alimentary Pharmacology & Therapeutics.  2006.
2.       Sokol, H., Seksik, P., Rigottier-Gois, L., Lay, C., Lepage, P., Podglajen, I., Marteau, P. and Doré, J.  Specificities of the fecal microbiota in inflammatory bowel disease.  Inflammatory Bowel Disease.  2006.
3.       Borody, TJ; George, L; Andrews, P; Brandl, S; Noonan, S; Cole, P; Hyland, L; Morgan, A; Maysey, J; Moore-Jones, D. Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome?. The Medical journal of Australia1989.
4.       Landy, J., Al-Hassi, H. O., McLaughlin, S. D., Walker, A. W., Ciclitira, P. J., Nicholls, R. J., Clark, S. K. and Hart, A. L.  Review article: faecal transplantation therapy for gastrointestinal disease. Alimentary Pharmacology & Therapeutics.  2011.
5.       Michael S. Silverman, Ian Davis, Dylan R. Pillai.  Success of Self-Administered Home Fecal Transplantation for Chronic Clostridium difficile Infection.  Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.  2010.
6.       S Angelberger, C Lichtenberger, C Gratzer, P Papay, C Primas, A Eser, A Mikulits, C Dejaco, G Novacek, H Vogelsang, W Reinisch.  Fecal transplantation in patients with moderately to severely chronic active ulcerative colitis (UC).  Gastroenterologie.  2012.
7.       Vermeire S , Joossens M , Verbeke K , et al. Pilot study on the safety and efficacy of faecal microbiota transplantation in refractory crohn's disease. Gastroenterology 2012.
8.       Anderson, J. L., Edney, R. J. and Whelan, K., Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease. Alimentary Pharmacology & Therapeutics, 2012.

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