Abstarct

In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.

摘要

在针对复发性艰难梭菌感染 (CDI) 的粪便微生物群移植 (FMT) 中，临床结果通常在 8 周后确定。我们假设肠道微生物群的变化早于该时间点，并分析了治疗 1 周后从 64 名诊断为复发性 CDI 并纳入随机临床试验的患者中获取的粪便样本，其中感染先于万古霉素进行 FMT 治疗（N = 24), 万古霉素 ( N = 16) 或非达霉素 ( N= 24). 与无反应者相比，FMT 后持续消退的患者微生物 α 多样性增加，瘤胃球菌科和毛螺菌科丰富，肠杆菌科减少，供体微生物群植入更明显，肠道微生物群失调得到解决。我们发现，构建的索引基于已识别的埃希氏菌属和布劳氏菌属的标记, 在第 8 周成功预测了临床结果，这举例说明了利用临床上可行的方法来预测治疗失败的方法。微生物群的变化仅限于接受 FMT 而不是抗生素单一疗法的患者，这表明 FMT 以不同于抗生素的方式赋予治疗反应。我们认为，在 FMT 后早期鉴定微生物群落结构对于预测对治疗的反应具有临床价值。