Abstract
Faecal microbiota transplantation (FMT) may contribute towards disease remission in ulcerative colitis (UC), but it is unknown which factors determine long-term effect of treatment. Here, we aimed to identify bacterial signatures associated with sustained remission. To this end, samples from healthy donors and UC patients—grouped into responders and non-responders at a primary end point (week 12) and further stratified by sustained clinical remission and relapse assessed at ⩾1-year follow-up were analysed, comparing the efficacy of FMT from either a healthy donor or autologous faeces. Microbiota composition was determined with a 16S rRNA gene-based phylogenetic microarray on faecal and mucosal samples, and functional profiles were predicted using PICRUSt with quantitative PCR verification of the butyrate production capacity; short-chain fatty acids were measured in faecal samples. At baseline, UC patients showed reduced amounts of bacterial groups from the Clostridium cluster XIVa, and significantly higher levels of Bacteroidetes as compared with donors. These differences were reduced after FMT mostly in responders. Sustained remission was associated with known butyrate producers and overall increased butyrate production capacity, while relapse was associated with Proteobacteria and Bacteroidetes. Ruminococcus gnavus was found at high levels in donors of failed FMT. A microbial ecosystem rich in Bacteroidetes and Proteobacteria and low in Clostridium clusters IV and XIVa observed in UC patients after FMT was predictive of poor sustained response, unless modified with a donor microbiota rich in specific members from the Clostridium clusters IV and XIVa. Additionally, sustained response was associated with restoration of the butyrate production capacity.
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Acknowledgements
We thank all laboratory technicians who performed HITChip, the trial nurses involved in the TURN trial and all participants who either received or donated faeces for FMT treatments. This work was supported by MLDS Grant 2011 (WO 11-17) to NGR and NWO-Spinoza Grant 2008 to WMdV. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Author contributions
CP was responsible for the study concept and design. The original study protocol was written by NR and CP. NR and CP predefined end points of the trial. CP and WdV obtained funding. NR was the executive investigator of the trial and MvdS was involved in the clinical work as a trial nurse. WdV, EZ, JH and SF were responsible for all microbiological experiments. LH and KK performed qPCR experiments on butyrate production capacity. PICRUSt experiments on functional capacity of the microbiota were carried out by JS. NR and SF performed statistical analyses. SF, NR, EZ, CP and GD drafted the manuscript. Critical revision of the manuscript was done by all coauthors. All authors had access to the study data and have reviewed and approved the final manuscript.
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Fuentes, S., Rossen, N., van der Spek, M. et al. Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation. ISME J 11, 1877–1889 (2017). https://doi.org/10.1038/ismej.2017.44
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DOI: https://doi.org/10.1038/ismej.2017.44
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