Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection
Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection
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DOI：
10.1038/ismej.2014.13
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发表时间：
2014-08-01
期刊：
影响因子：
11
通讯作者：
de Vos, Willem M.
中科院分区：
文献类型：
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作者：
Fuentes, Susana;van Nood, Els;de Vos, Willem M.
复发性艰难梭菌感染（CDI）可以通过输注健康供体粪便悬浮液来有效治疗。然而，尚不清楚哪些因素决定治疗效果。通过使用系统发育微阵列平台，我们评估了健康供体移植到不同患者之前、之后和随访期间粪便微生物群的组成、多样性和动态，以阐明粪便输注的作用机制。对 9 名复发性 CDI 患者的粪便样本进行了微生物群的整体组成和网络分析。在十二指肠供体粪便输注之前和之后以及 10 周的随访期间进行了分析。将微生物群数据与健康捐赠者的微生物群数据进行比较。所有患者均顺利康复。他们的肠道微生物群从以变形菌和芽孢杆菌为主的低多样性患病状态，转变为类似于健康捐赠者的更加多样化的生态系统，以拟杆菌和梭菌群为主，包括产生丁酸的细菌。我们确定了特定的多物种网络和特征微生物群，这些网络和特征微生物群在治疗后要么被耗尽，要么被恢复。随着时间的推移，这些变化持续存在。对治疗前后患者微生物群的全面深入分析揭示了从患病状态到健康状态的治疗重置。鉴定构成艰难梭菌过度生长的生态位的微生物群，以及驱动健康肠道微生物群重新安装的微生物群，可能有助于开发预测复发和治疗结果的生物标志物，确定可能导致有针对性的治疗策略的最佳微生物群组成。
Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.