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Letter: faecal microbiota transplantation for irritable bowel syndrome—which improvements are required? Authors' reply

We thank El-Salhy et al their interest in our study1,2 and for contributing to the active discussion on how to improve the designs of future faecal microbiota transplantation (FMT) studies.3-6 We showed a mild transient benefit of FMT administered once via colonoscopy for irritable bowel syndrome (IBS) patients, although the difference was not significant when compared to placebo.2 Still, FMT for this patient group shows promise, as also shown by the good results achieved in the clinical trial of El-Salhy et al, showing that a single FMT via gastroscopy resulted in a significant symptom reduction three months after treatment.7 The good results were associated with careful donor selection and the healthy lifestyle of the donor was discussed. However, the detailed description of intestinal microbiota of the donor was not reported and would probably highlight novel donor preferences for successful FMT for IBS. We agree that careful donor selection is important, since clear differences between donors were demonstrated when treating ulcerative colitis.8 However, such evidence is lacking for IBS patients. We suggest comparing the efficacy of different donors in FMT trials to enable detecting which bacteria, metabolites or other components are associated with positive outcomes, or alternatively which individual factors may be crucial for successful donor selection. It is still unclear which faecal components carry the therapeutic effect for IBS patients. We showed that a single FMT altered the microbiota composition although it did not result in sustained relief of symptoms.2 To understand this phenomenon, we require further knowledge of the effective microbiota of the donor as well as the microbial community of the patient. The transplanted microbes may alter their activity as a result of different diet or host-microbe interaction in the new host. For example, the production of beneficial metabolites could be decreased, and inert or harmful substances increased. Also, faecal preparation for transplantation may induce shifts in microbial balance and activity, and these procedures should also be considered. Because of microbial changes due to the FMT preparation processes, we encourage sham-controlled trials using an inert placebo instead of using autologous faeces as placebo. The optimal diet of a donor is not yet established. Therefore, it is important that future studies collect and share detailed data of donorś diet coupled with assessment of gut microbiota and metabolites. We suggest that donors adhere with general guidelines of healthy, local and sustainable diet,9 which contains a large amount of plant-based fibres. However, we do not support the use of dietary supplements for subjects with a healthy diet. In order to understand the discrepancy in the success of FMT trials for IBS, we encourage comparison of different routes and doses of FMT administration and of the selection criteria and microbiota of the donors across different clinical trials. Finally, to unveil the host-microbiota interaction, we must link microbial dynamics with changes in symptoms.