Step-by-step guide to faecal microbiota transplantation

From a microbiological point of view, faecal microbiota transplantation (FMT) represents an almost perfect solution to treating disorders of the flora of the gastrointestinal tract. The gut contains a complex biome of many different bacteria which all form an important part of the flora. Instilling a real mixture of these bacteria in the form of a faecal transplant in order to correct an imbalance makes physiological sense.

FMT is of interest to gastroenterologists as it may provide a genuinely novel approach to treating a number of gastrointestinal diseases and, in particular, inflammatory bowel disease (IBD). IBD patients have been shown to have dysbiotic microbiomes compared with controls, characterized by changes in Firmicutes and Proteobacteria. A dysbiosis is likely to alter microbiome function and may predispose to, or cause, enteric disease.

This article follows the journey of a typical but fictional patient; a young man with a four-year history of severe ulcerative pancolitis who had tried and failed all medical therapy. The gastroenterology team were considering a referral to a colorectal surgeon for a subtotal colectomy.

Step 1 Patient selection
Interestingly, despite the aesthetic concerns that many doctors and the general public have with the procedure, in our practice most patients are happy to consider FMT. In the CDI group they have usually exhausted antibiotic treatments or have had several admissions to hospital so are happy to consider any treatment.

In our experience IBD patients usually request FMT, having read about it in the media, in a bid to avoid surgery or potent immunosuppressants.

Step 2 Donor selection
A donor less than 50-years-old is preferred as the microbiome becomes less diverse with age. This may reduce the effectiveness of FMT. As relatives are likely to carry a similar microbiome dysbiosis, a non-related donor is recommended.

Step 3 Screening
There is a risk of transferring an infectious organism when giving a patient a non-sterile sample from another person. This includes not only the obvious gastrointestinal pathogens such as the bacterial, viral and parasitic causes of gastroenteritis but also HIV, hepatitis B, hepatitis C and CMV. A rigorous screening process of the donor faeces is paramount to reduce transplant morbidity.

Safety concerns were recently highlighted by a case report of CMV colitis probably contracted by home FMT from an unscreened donor (Hohmann et al., 2014).

No screening consensus exists yet but a pre-procedure screening protocol is suggested in Table 1. Screening of the recipient is less critical than that of the donor but background infection testing of the recipient is advised in case serological conversion or acute infection post-FMT occurs.

Step 4 Choice of administration route
Routes of administration are via colonoscopy, nasojejunal tube (NJT) or rectal enema. Choice of route will depend on the site of disease, patient co-morbidities and patient preference.

Colonoscopy delivers the transplant directly into the right colon but carries a risk of perforation. Therefore, the risk of the procedure may outweigh the benefits, particularly in patients with severe CDI or severe colitis. NJT delivers the transplant into the right colon but has the theoretical potential for causing small bowel bacterial overgrowth in the future and suffers from greater patient aesthetic concerns than the other routes. Finally, an enema is safe and more aesthetically acceptable but is unlikely to reach the right colon and therefore may not be as effective.

Step 5 Patient preparation
Bowel preparation should be undertaken for all patients undergoing FMT regardless of the administration route. Excellent bowel preparation is paramount to expel as much of the patient’s own microbiota as possible. Theoretically, this will increase the chances of the transplanted microbiota repopulating the patient.

Image of colon

Image of colon

 

Step 6 Donor preparation
The donor is provided with a wide diameter disposable mixing jar with a screw-on lid in which to deposit and transport their sample to the hospital. Ideally the donation should be between 100g and 200g. Many donors require a gentle stimulant laxative (e.g., Senna) the night before donation to enable delivery to the microbiology laboratory before 9am.

Step 7 Transplant preparation
The laboratory preparation of the faecal sample is relatively straightforward. The sample should be handled in a clean area of the laboratory in order to prevent the sample becoming contaminated with gastrointestinal pathogens from the laboratory environment.

The sample can then be emulsified in 250ml of sterile normal saline, passed through sterile gauze in order to remove particulate matter, and returned to the clinical area in the appropriate device for administering to the patient; either syringes for colonoscopy, enteral feeding containers for NJT or enemas.

Step 8 Transplant delivery
Before the delivery of the transplant, regardless of the route chosen, the patient should be prescribed 4mg loperamide (an anti-diarrhoeal agent) and encouraged not to defaecate for as long as possible.

Colonoscopy – a standard colonoscopy is performed to the terminal ileum with minimal insufflation of air and suction of any debris on insertion. The transplant is flushed down the biopsy channel into the lumen in the following proportions: ¼ into the terminal ileum, ½ into the caecum and ¼ into the transverse colon.

NJT – the patient should have clear fluids only in the preceding hours. The transplant is connected to the NJT and given at a rate of 50ml/hr until complete.

Enema – once inserted, the patient is encouraged to roll gently on the bed to encourage the transplant to reach the right colon.

Step 9 Post-transplant
Few post-transplant complications have been reported but abdominal pain, loose stool and fever are the most common which usually require conservative treatment. In CDI, clinical improvement is expected within 24−48 hours but in non-infectious aetiology the time to improvement is likely to be days to weeks.
FMT is in its infancy and the spectrum of disease which it will treat is not yet defined. It has the potential to be effective and cheap but carries a significant risk of transmission of infection and the cost of screening is not insignificant. Several centres are creating ‘stool banks’ containing only highly vetted and screened stools from known donors which will significantly reduce the risks and improve reliability of FMT.

The role for FMT in CDI is clear but the evidence for FMT in other disease processes is currently lacking. However, there are numerous ongoing trials of which the results are eagerly expected. As our understanding of the role of bacteria in immunology and development increases, potential targets for bacteriotherapy may arise.

FMT in its current state involves the complete replacement of the host microbiota. Further research into the microbiota in health and disease may define specific deficiencies of the host and instead of replacing the whole microbiota, it may be possible to replace only targeted bacteria.

Methods of delivery are rapidly evolving and it is entirely feasible for pH-controlled colonic release capsules containing faeces or specific bacterial cocktails to be available in the next few years.

Jonathan Digby-Bell, Gastroenterology Department, Frimley Park Hospital, Surrey David Garner, Microbiology Department, Frimley Park Hospital, Surrey



Categories: Feature Articles

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