University of Houston College of Pharmacy, USA.
Baylor College of Medicine, USA.
Anaerobe. 2021 Aug;70:102387. doi: 10.1016/j.anaerobe.2021.102387. Epub 2021 May 24.
Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years.
Seven stool samples were obtained between 2016-18 while the patient underwent five FMTs. Stool samples were cultured for C. difficile and underwent microbial characterization and functional gene analysis using shotgun metagenomics. C. difficile isolates were characterized through ribotyping, whole genome sequencing, metabolic pathway analysis, and minimum inhibitory concentration (MIC) determinations.
Growing ten strains from each sample, the index and first four recurrent cultures were single strain ribotype F078-126, the fifth was a mixed culture of ribotypes F002 and F054, and the final culture was ribotype F002. One single nucleotide polymorphism (SNP) variant was identified in the RNA polymerase (RNAP) β-subunit RpoB in the final isolated F078-126 strain when compared to previous F078-126 isolates. This SNV was associated with metabolic shifts but phenotypic differences in fidaxomicin MIC were not observed. Microbiome differences were observed over time during vancomycin therapy and after failed FMTs.
This study highlights the importance of antimicrobial stewardship in patients receiving FMT. Continued antibiotics play a destructive role on a transplanted microbiome and applies selection pressure for resistance to the few antibiotics available to treat CDI.
粪便微生物群移植（FMT）旨在通过重建健康的微生物组和恢复定植抗性来治疗艰难梭菌感染（CDI）。尽管一次输注后通常有效，但持续存在微生物组紊乱的患者可能需要多次 FMT。在这项 N-of-1 研究中，我们使用系统生物学方法评估了一名接受慢性抑制性抗生素治疗的患者的 CDI，该患者在两年内进行了四次 FMT 但均未成功。
在 2016-18 年期间，当患者接受五次 FMT 时，共获得了七份粪便样本。对粪便样本进行艰难梭菌培养，并通过 shotgun 宏基因组学进行微生物特征分析和功能基因分析。通过核糖体分型、全基因组测序、代谢途径分析和最小抑菌浓度（MIC）测定对艰难梭菌分离株进行特征分析。
从每个样本中培养出十株菌，指数和前四个复发性培养物均为单一菌株核糖体分型 F078-126，第五个是 F002 和 F054 核糖体型的混合培养物，最后一个培养物是 F002 核糖体型。与之前的 F078-126 分离株相比，最后分离的 F078-126 菌株的 RNA 聚合酶（RNAP）β亚基 RpoB 中发现了一个单核苷酸多态性（SNP）变体。该 SNP 与代谢变化有关，但在 fidaxomicin MIC 方面没有观察到表型差异。在万古霉素治疗期间和 FMT 失败后，随着时间的推移，微生物组差异也发生了变化。
本研究强调了在接受 FMT 的患者中进行抗菌药物管理的重要性。持续使用抗生素对移植的微生物群具有破坏性作用，并对治疗 CDI 的少数抗生素产生耐药性选择压力。
