Faecal microbiota transplantation (FMT) is the infusion of a faecal suspension containing the microbiota from a healthy donor into the gastrointestinal tract of a recipient with the aim of treating disease. FMT is effective in the treatment of recurrent Clostridium difficile infections, the most frequent cause of nosocomial diarrhoea, but its success in the treatment of other diseases that are caused by microbial dysbioses such as ulcerative colitis is modest, with variations in effectiveness. In some cases, FMT success has been found to be dependent on the diversity and composition of the donor microbiota, suggesting the existence of FMT ‘super-donors’.
In a recent study, researchers at the University of Auckland, New Zealand, examined the findings from previous FMT trials to understand why the faeces from specific donors are better for treating certain conditions than others ( Frontiers in Cellular and Infection Microbiology , 21 Jan 2019). By investigating what makes someone a suitable donor for FMT, Justin O’Sullivan and colleagues suggest that a high diversity of the donor’s gut microbiota seems to the best predictor of the response to FMT in the recipient. For certain conditions such as inflammatory bowel disease, FMT efficacy seems to depend on the ability of the donor to provide taxa that can restore metabolic deficits in recipients that are important for a healthy gut. In some studies, it was suggested that viruses in the stool could have a role in treating specific conditions. Compatibility between the donor and recipient was also found to be an important factor; for example, the immune response of the recipient to the donor stool, and the composition of the recipient’s gut microbiota before the transplant. Moreover, in addition to underlying genetic differences between donors and recipients, the diet of the recipient and exposure to drugs are also likely to affect the long-term efficacy of FMT. The team conclude that the existence of FMT super-donors is not yet supported and argue that there is no ‘one stool fits all’ approach, and a more personalized approach could improve the success of FMT. Commenting on the study, Rob Knight from the University of California San Diego, United States, said “Strategies to find super-donors whose stool is especially effective as a curative are still in their infancy, although progress on this topic – or making synthetic super-donors from the stool of many people – could greatly improve application of [faecal transplants],” ( The Guardian , 21 Jan 2019).
O’Sullivan and colleagues also highlighted the lack of large randomized controlled clinical trials. A recent randomized, double-blind study of 73 adults with ulcerative colitis found that a short duration of FMT could induce remission of the disease with a 32% remission rate compared with 9% with placebo ( The Journal of the American Medical Association , 15 Jan 2019). It was announced that a research consortium began enrolling patients in a clinical trial examining whether FMT is safe and can prevent recurrent C. difficile-associated disease (CDAD) ( National Institutes of Health News , 14 Jan 2019). Investigators aim to enrol 162 volunteers who have had at least two episodes of CDAD within the previous six months. To understand the long-term outcomes of FMT, all participants will be monitored for adverse side effects for three years after treatment.
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York, A. FMT in the clinic. Nat Rev Microbiol 17, 127 (2019). https://doi.org/10.1038/s41579-019-0157-x
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