Fecal Transplantation: Any Real Hope for Inflammatory Bowel Disease?

Paul Moayyedi

Disclosures

Curr Opin Gastroenterol. 2016;32(4):282-286. 

In This Article

Abstract and Introduction

Abstract

Purpose of review Fecal microbiota transplant (FMT) has emerged as an important treatment for antibiotic resistant or recurrent Clostridium difficile infection. There has been a great deal of media coverage of the efficacy of FMT, and patients with inflammatory bowel disease (IBD) understandably wonder if this approach would also work for them. There are also instructions on 'do it yourself' FMT therapy on the web. It is important to understand whether there is evidence that this approach is effective in IBD so that we can advise our patients appropriately.

Recent findings Systematic reviews have identified four case series involving 27 ulcerative colitis patients with a pooled remission rate of 24% (95% confidence interval (CI) = 11–45%). Two randomized controlled trials evaluating a total of 123 active ulcerative colitis patients have given conflicting results but the pooled data do suggest benefit with a number needed to treat of 6 (95% CI = 3–33). There are four case series involving 38 patients with Crohn's disease with a clinical response in 60.5% (95% CI = 28–86%). There are no randomized trials in Crohn's disease.

Summary At present there are insufficient data to recommend FMT in IBD, and patients certainly should not be administering this themselves. This remains an interesting approach to treating IBD and more studies are needed to establish the optimal method of delivery as well as randomized, placebo controlled trials to establish the efficacy of FMT.

Introduction

The cause of inflammatory bowel disease (IBD) is unknown but it is generally believed that IBD results from the interaction between a disordered immune system and the environment in a genetically susceptible host.[1] There are over 160 loci containing susceptibility genes for IBD[2] and these have provided information on immune pathways that may drive the disease. Most current therapies focus on suppressing the immune system, and these have been effective at inducing remission and preventing relapse of IBD.[3] The majority of IBD therapeutic research continues to focus on this model with drugs that suppress the immune system,[4] and other approaches relating to precision medicine in which genotypic and phenotypic characteristics are identified that might predict response to immunosuppressive agents.[5] In contrast, there is a paucity of research on what might be driving the aberrant immune response. This myopia is concerning as future drugs that suppress the immune system are likely to be expensive and need to be taken long term to reduce recurrence of the disease. The approach of suppressing the immune system is also very unlikely to lead to a cure of IBD, whilst focusing on what is driving the immune system is more likely to lead to a cure of these diseases. A major challenge is discovering what environmental agents might be responsible for IBD. One possibility is that IBD is caused by an immune response to food or other ingested agents. This seems unlikely, however, as the most common site of inflammation for Crohn's disease is the terminal ileum and inflammation starts in the rectum in ulcerative colitis.[6] Neither of these sites would be the most obvious areas where immune responses to food would be initially focused. A more likely candidate is the gut microbiome and this has been the focus of recent observational studies.[7]

There have been a number of small case control studies that have compared the gut microbiome in IBD with healthy controls and all have shown statistically significant differences both in Crohn's disease[8] and ulcerative colitis.[9] The prevailing theory is that the immune dysregulation is driven by dysbiosis of the gut microbiota. The problem is that all studies report changes in different bacterial families[7–11] and any 'statistically significant' results could be due to multiple different testing rather than any real differences in the microbiome among groups. Whilst the term dysbiosis is used regularly there is no gut microbiome composition that can be defined as abnormal and it is unlikely that this will be delineated in the near future. A more fruitful approach to exploring the role of the gut microbiome in IBD is to manipulate it and evaluate whether this improves the disease. Systematic reviews of randomized trials have shown that antibiotics may be effective in inducing remission both in ulcerative colitis and Crohn's disease.[12] However, antibiotics are not recommended for therapy in IBD, as there is no clear signal as to which antibiotics are effective. The main problem is that antibiotics are a targeted method of manipulating the microbiome and this is not a sensible approach when there is a very limited understanding of how the gut microbiota is driving the immune response in IBD. A more rational approach in this context would be to replace the microbiome of an IBD patient with that from a healthy person. This is what fecal microbial transplantation (FMT) attempts to achieve, and this has been very successful in treating antibiotic resistant Clostridium difficile infection. What is the evidence that FMT is useful in treating IBD?

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