Faecal Microbiota Transplantation for Inflammatory Bowel Disease
The use of faecal transplantation as a therapeutic tool for not only Clostridium Difficile Infection but as a mechanism for changing the composition of colonic microbiota for the purpose of resolving numerous persistent inflammatory conditions is starting to gain increased interest in the research and medical communities.
Medscape recently published a summary of many of the key areas and I have extracted and edited a small section for peoples review.
The authors of the original paper are Els van Nood, Peter Speelman, Max Nieuwdorp, Josbert Keller and it was published in Currrent Opinion Gastroenterology. Any errors or ommissions are my responsibility.
The first reports of faecal microbiota transplantation in the colon for ulcerative colitis in literature date from 1989. Only a handful of cases have been published in case reports. With the interest in the role of the microbiota in the pathogenesis of IBD, FMT is now considered as one of the potential ‘novel therapies under investigation’ for ulcerative colitis. A recent study of 10 children with ulcerative colitis treated with FMT showed 78% clinical response within 1 week; clinical remission in 33% of patients; and only mild and self-limiting adverse events.
Caution is required, as in a small group of four patients with Crohn’s disease, adverse effects (transient fever, abdominal pains, bloating, and no clinical improvement with only transient effects on the host’s faecal microbial composition) were reported 2 months after treatment with FMTs.
There are no results of randomised trials available supporting the efficacy of FMT for ulcerative colitis or Crohn’s disease, but several studies are recruiting patients (clinical trials.gov). A blinded randomised trial will end this year in the Netherlands (Dutch Trial Registry, NTR2862, the TURN trial). Until the results of those trials become available, use of FMT in IBD patients should be considered strictly experimental.
Optimal Protocol of Fecal Microbiota Transplantation
There is no consensus on the optimal protocol for FMT. Faeces can be infused both in the upper or lower gastrointestinal tract. Approximately one-third of patients have received faeces through a gastric or nasoduodenal tube, two-thirds through an enema or colonoscope.  The overall reported success rate is around 90%. As it is difficult to compare the different protocols and strategies in different case series and case reports, there is currently no consensus on the preferred route of infusion.
Historically, the majority of successfully treated patients received only one treatment with donor faeces, although small early series reported multiple infusions.
If given for Clostridium Difficile Infection (CDI), approximately 80% of patients received antibiotic treatment for CDI prior to the FMT. For other indications [metabolic syndrome, irritable bowel syndrome (IBS)] there are no reports in the literature of antibiotic pre-treatment.
A minority of patients receive an oral whole bowel lavage prior to infusion of faeces. Although it certifies normal passage of fluids prior to infusing faeces, there is no study that compared donor faeces with or without a whole bowel lavage. With regard to donor preference, most patients receive donor faeces from partners or relatives, whereas healthy volunteers are used in a minority of cases. Experience indicates, there is no relation between sex-matched or relative-matched faeces and success rates.
Preparation of Faeces
Freshly produced donor stool (200–300 g) is processed and infused preferably as quickly as possible. In case series, this is mostly done within 6 h of passage. Faeces mostly are dissolved in sterile saline. Water and other diluents (e.g. yogurt or milk) have also been described as vehicle. Faeces have to be liquefied, to allow infusing the solution in the bowel. Unfolded gauzes, paper funnels, and cloths all have been used to strain debris. In case series, the amount of faeces used varies from 15 to 300 g, with a trend towards improved outcome using larger volumes of prepared solution. Whether, faeces should be prepared in an anaerobic environment to preserve as much obligate anaerobic bacteria as possible is unknown. Most laboratories lack anaerobic chambers, and previous success rates are obtained with aerobic preparation. Nevertheless it seems advisable to cover faeces as soon as possible with saline.
As more data become available about the use of standardised frozen stool samples, outcomes do not seem to be affected by this procedure in case series. The logistic advantage of frozen stool stored in advance is obvious, as it can be used directly when necessary.
Protocol for Screening of Donors
With regard to screening of potential donors, it is important that individuals with an increased risk of any (sexually) contractible diseases are excluded in order to reduce transmission of (otherwise unknown) pathogens. Any risk of a recently contracted infectious disease that is still in its window phase (HIV, hepatitis) warrants exclusion of the potential donor. Questions regarding travel history, sexual behaviour, previous operations, blood transfusions, piercings, and all other interventions that might contribute to carriage of an infectious disease should be asked.7 Although the potential risk of transferring an infectious disease is probably limited when using a partner or spouse as donor, screening is always preferred. Moreover, keeping in line with current blood transfusion protocols, the use of thoroughly screened standardised frozen stool batches in faecal transplantation might have several logistical advantages over the use of fresh donor stool, with regard to the aforementioned window phase.
Example of Screening
|Table 1. Screening of donors|
|1. Initial screening Questionnaire addressing risk factors for potentially transmittable disorders|
|2. Donor screening Blood|
|Cytomegalovirus (IgG and IgM)|
|Epstein–Barr virus (VCA IgM, VCA IgG, VCA, anti-EBNA)|
|Hepatitis (total antibodies, if positive and not vaccinated also hepatitis IgM)|
|Hepatitis (HbsAg, anti-HbsAg, anti-HBcore)|
|HIV types and|
|Human T-lymphotropic virus type and II|
|Treponema pallidum (TPHA)|
|Entamoeba histolytica (agglutination and dipstick test)|
|Strongyloides stercoralis (ELISA)|
|Bacteriological evaluation by local standards|
|Parasitological evaluation by local standards (triple faeces test or PCR)|
|Test for Clostridium difficile (toxin ELISA and culture or PCR)|
|3. One day before donation of faeces Questionnaire addressing current stool frequency and pattern, general health, use of antibiotics, travel history and (recent) sexual behaviour since initial screening|
|anti-EBNA, anti-Epstein-Barr virus nuclear antigen; VCA, viral capsid antigen.|
The risk of transmitting a non-infectious disease has also to be taken into account; with the increased interest for the interaction between microbiota and its influence on a large number of diseases (Crohn’s disease, ulcerative colitis, autoimmune diseases, irritable bowel syndrome, and celiac disease) and the possible causative role of microbiota, patients with any of the above mentioned diseases should be excluded as potential donor.
Potential Adverse Events
The potential adverse events from a FMT can be related to the procedure itself or related to the infusion of another human’s faeces. Procedurally, both routes have their specific (mostly theoretical) risks. Colonoscopy can only be performed by a trained physician, and has a small risk of perforation or bleeding. Infusing faeces through a duodenal tube is perceived to be less invasive and less strenuous than through colonoscopy, but there is a potential risk of vomiting if bowel passage is hampered. Donor faeces should therefore be infused slowly. Most case series lack reporting adverse effects.6 In the randomised trial for CDI, no significant differences in adverse events among the three study groups were observed, except for mild diarrhoea and abdominal cramping in the infusion group on the day of infusion. Transfer of infectious diseases has not been reported.
 Kunde S, Pham A, Bonczyk S, et al.Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. J Pediatr Gastroenterol Nutr 2013; 56:597–601 View Abstract
 Vermeire S, Joossens M, Verbeke K, Hildebrand F, et al.Sa1922 pilot study on the safety and efficacy of faecal microbiota transplantation in refractory Crohn’s disease. Gastroenterology 2012; 142 (5 Suppl 1):S-360
 Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficileinfection. Clin Infect Dis 2011; 53:994–1002 View Abstract
 van Nood E, Speelman P, Kuijper EJ, Keller JJ. Struggling with recurrent Clostridium difficileinfections: is donor faeces the solution? Euro Surveill 2009; 14:19316 *The first randomized trial in which FMT is given for recurrent CDI. View Abstract
 Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficileinfection. Am J Gastroenterol 2012; 107:761–767 View Abstract
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