Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection
Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection
复制标题
DOI：
10.1053/j.gastro.2016.11.010
复制
发表时间：
2017-03-01
期刊：
影响因子：
29.4
通讯作者：
Schreiber, Stefan
中科院分区：
文献类型：
--
作者：
Ott, Stephan J.;Waetzig, Georg H.;Schreiber, Stefan
背景与目的：粪便微生物群移植（FMT）是治疗复发性艰难梭菌感染（CDI）的一种高效疗法。然而，转移不确定的活细菌会带来感染性和代谢性或恶性疾病的不可控制的风险，特别是在免疫功能低下的患者中。我们研究了无菌粪便微生物（含有细菌碎片，蛋白质，抗菌化合物，代谢产物和寡核苷酸/DNA），而不是完整的微生物，是否对CDI患者有效。方法：我们在石勒苏益格-荷尔斯泰因大学医院（基尔，德国）内科I的5例有症状的慢性复发性CDI患者中进行了一项临床病例系列研究，以探讨粪便滤液转移（FFT）的效果。患者随访至少6个月，最长33个月。从患者选择的5名供体收集粪便，并根据FMT标准进行充分表征。对粪便进行无菌过滤，以去除小颗粒和细菌;滤液通过鼻空肠管一次性输注给患者。在FFT前和FFT后1周和6周从患者收集粪便样品。比较了供体和患者的微生物组、病毒组和蛋白质组谱。结果：在所有5例患者中，FFT恢复了正常的排便习惯，并消除了CDI症状至少6个月。对选定的FFT滤液进行的蛋白质组分析显示，没有与治疗功效相关的明显候选蛋白质。16 S核糖体RNA基因测序检测到不同的细菌DNA签名的细菌。对发现可减轻CDI症状的滤液中的病毒样颗粒的分析显示了噬菌体的复杂特征。对来自接受者的粪便样品的细菌遗传学和病毒组谱分析表明FFT后微生物和病毒群落结构的纵向变化。结论：对5名CDI患者的初步调查显示，从供体粪便（FFT）转移无菌粪便，而不是粪便微生物群，足以恢复正常的排便习惯并消除症状。这一发现表明，细菌成分，代谢产物或噬菌体介导的FMT的许多影响，FFT可能是一种替代方法，特别是对免疫功能低下的患者。
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI. METHODS: We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared. RESULTS: In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT. CONCLUSIONS: A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that FFT might be an alternative approach, particularly for immunocompromised patients.