title: Microbial shifts and signatures of long-term remission in ulcerative colitis after faecal microbiota transplantation.
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.
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Susana
authors.initials: S
authors.lastname: Fuentes
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Noortje G
authors.initials: NG
authors.lastname: Rossen
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mirjam J
authors.initials: MJ
authors.lastname: van der Spek
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Jorn Ha
authors.initials: JH
authors.lastname: Hartman
authors.affiliation: RPU Immunobiology, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Huuskonen
authors.affiliation: RPU Immunobiology, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Korpela
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Salojärvi
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Steven
authors.initials: S
authors.lastname: Aalvink
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.|RPU Immunobiology, Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Geert R
authors.initials: GR
authors.lastname: D'Haens
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
mesh_terms: D000328:Adult; D001419:Bacteria / Q000235:genetics; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D010802:Phylogeny