Systematic Review: Faecal Microbiota Transplantation in the Management of Inflammatory Bowel Disease

J. L. Anderson; R. J. Edney; K. Whelan

Disclosures

Aliment Pharmacol Ther. 2012;36(6):503-516. 

In This Article

Abstract and Introduction

Abstract

Background The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD). Faecal microbiota transplantation (FMT) has been used for the management of IBD as well as infectious diarrhoea.
Aim To undertake a systematic review of FMT in patients with IBD.
Methods The systematic review followed Cochrane and PRISMA recommendations. Nine electronic databases were searched in addition to hand searching and contacting experts. Inclusion criteria were reports (RCT, nonrandomised trials, case series and case reports) of FMT in patients with IBD.
Results Of the 5320 articles identified, 17 fulfilled the inclusion criteria, none of which were controlled trials. There were nine case series/case reports of patients receiving FMT for management of their IBD, and eight where FMT was for the treatment of infectious diarrhoea in IBD. These 17 articles reported on 41 patients with IBD (27 UC, 12 Crohn's, 2 unclassified) with a follow-up period of between 2 weeks and 13 years. Where reported, FMT was administered via colonoscopy/enema (26/33) or via enteral tube (7/33). In patients treated for their IBD, the majority experienced a reduction of symptoms (19/25), cessation of IBD medications (13/17) and disease remission (15/24). There was resolution of C. difficile infection in all those treated for such (15/15).
Conclusions Whilst the available evidence is limited and weak, it suggests that faecal microbiota transplantation has the potential to be an effective and safe treatment for IBD, at least when standard treatments have failed. Well-designed randomised controlled trials are required to investigate these findings.

Introduction

Inflammatory bowel disease (IBD) is a chronic, relapsing and remitting disease, with both ulcerative colitis (UC) and Crohn's disease (CD) causing significant morbidity.[1] The precise aetiology of IBD is unclear, however, its development, progression and phenotype are multifactorial with genetics and environment playing a role.[2] There is increasing evidence supporting a microbial influence in the pathogenesis of IBD resulting from an inappropriate immune response towards components of the commensal microbiota.[2,3] Although there is inconclusive evidence for a specific pathogen causing IBD,[2] evidence suggests that there is a reduced diversity of luminal microbiota in IBD, with a decrease in Firmicutes such as bifidobacteria, lactobacillus and Faecalibacterium prausnitzii and an increase in mucosal-adherent bacteria.[4]

Firmicutes are major producers of short-chain fatty acids (SCFA's) such as butyrate, which is a substrate with immunoregulatory properties.[4] Indeed, whilst not conclusive, studies have suggested possible benefits of butyrate enemas when used as a supplement to standard drugs, particularly in refractory UC.[5,6]

The treatment of IBD is rapidly evolving and many conventional and novel drug treatments have proven efficacy, including steroids, aminosalicylates, immunosuppressants and biological therapies.[7] However, some patients become refractory to standard management and some have significant adverse side effects with many patients requiring surgery.[8,9] Despite medical treatment, a significant number of patients live with mild active symptoms and have a poor quality of life.[7,10]

Given the role of the gastrointestinal microbiota in driving inflammation in IBD, treatments that manipulate the microbiota have been investigated including the use of probiotics and prebiotics, with variable evidence for their efficacy.[11,12] An additional alternative treatment for the management of IBD is faecal microbiota transplantation (FMT), which is the transfer of gastrointestinal microbiota from a healthy donor, via infusion of a liquid stool suspension, to restore the intestinal microbiota of a diseased individual.[13–15] Although it was first documented back in 1958,[16] it has recently become prominent as a treatment for refractory and recurrent Clostridium difficile infection. Two systematic reviews have recently been published in relation to FMT for the management of C. difficile. They failed to identify any controlled trials, although a number of case series and case reports indicated FMT as a potentially effective therapy where standard treatments had failed.[13,17] Interestingly, C.difficile infection is more common in patients with IBD,[18] with one study reporting a higher prevalence among patients with UC (3.7%) and CD (1.1%) compared with the background general population (0.5%).[18,19] Symptoms may mimic an exacerbation of IBD or precipitate a genuine relapse.

Faecal microbiota transplantation is also being used as a therapy in IBD with reports of patients with positive outcomes. However, there is currently a lack of cohesive assimilation of the available information on which to inform future robust clinical trials. The aim was to undertake a systematic review of FMT in patients with IBD to provide clinicians with a thorough and clear summary of the available evidence on which to guide current practice and future research.

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