Fuentes Susana, Rossen Noortje G, van der Spek Mirjam J, Hartman Jorn Ha, Huuskonen Laura, Korpela Katri, Salojärvi Jarkko, Aalvink Steven, de Vos Willem M, D'Haens Geert R, Zoetendal Erwin G, Ponsioen Cyriel Y
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
Department of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
ISME J. 2017 Aug;11(8):1877-1889. doi: 10.1038/ismej.2017.44. Epub 2017 Apr 11.
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.
粪便微生物群移植（FMT）可能有助于溃疡性结肠炎（UC）病情缓解，但尚不清楚哪些因素决定治疗的长期效果。在此，我们旨在识别与持续缓解相关的细菌特征。为此，我们分析了健康供体和UC患者的样本，这些患者在主要终点（第12周）分为反应者和无反应者，并在≥1年的随访中根据持续临床缓解和复发情况进一步分层，比较了来自健康供体或自体粪便的FMT疗效。使用基于16S rRNA基因的系统发育微阵列对粪便和黏膜样本进行微生物群组成分析，并使用PICRUSt预测功能谱，通过定量PCR验证丁酸盐产生能力；在粪便样本中测量短链脂肪酸。基线时，UC患者与供体相比，梭菌属 XIVa 簇的细菌数量减少，拟杆菌门水平显著更高。FMT后这些差异大多在反应者中有所减少。持续缓解与已知的丁酸盐产生菌及总体丁酸盐产生能力增加有关，而复发与变形菌门和拟杆菌门有关。在FMT失败的供体中发现高水平的纤细瘤胃球菌。FMT后在UC患者中观察到的富含拟杆菌门和变形菌门、梭菌属IV和XIVa簇含量低的微生物生态系统预示着持续反应不佳，除非用富含梭菌属IV和XIVa簇特定成员的供体微生物群进行改善。此外，持续反应与丁酸盐产生能力的恢复有关。
