Effect of antibiotic pre-treatment on the engraftment efficiency in mice

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). In addition, it is currently considered as a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects microbiota dysbiosis associated with rCDI and the engraftment of donor microbiota is likely to play a key role in the treatment success. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. rCDI patients have typically undergone multiple antibiotic treatments prior to FMT, and present with extensive microbiota dysbiosis. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT for the engraftment of donor microbiota. We conducted a pre-clinical study of FMT between two healthy strains of mice, to mimic interindividual FMT between human subjects.Microbiota composition was assessed by high-throughput 16S rDNA amplicon sequencing. Our results showed that Ab-treatment strongly diminished microbiota before FMT, but didn´t increase the overall similarity of the recipient´s microbiota to that of the donor´s after FMT, as compared to control treatment. However, Bifidobacterium and several other taxa, which were higher in the donor mice, showed increased abundance in recipient mice that were pre-treated with Ab. In conclusion, pre-treatment with broad-spectrum antibiotics didn´t improve the overall engraftment of donor microbiota, but improved the engraftment of specific taxa including Bifidobacterium.

粪便微生物群移植（Fecal microbiota transplantation, FMT）是治疗复发型艰难梭菌感染（recurrent Clostridioides difficile infection, rCDI）的有效疗法。此外，目前其被视为多种肠道及全身性疾病的潜在治疗手段。FMT可纠正与rCDI相关的微生物群失调，供体微生物群的定植是治疗成功的关键影响因素。针对rCDI以外的疾病适应证，FMT的治疗效果仅为中等。该现象的部分原因可能是：非rCDI患者的常驻宿主微生物群具有更强的恢复能力。复发型艰难梭菌感染患者通常在接受FMT前已接受过多轮抗生素治疗，且存在广泛的微生物群失调。本研究探讨了广谱抗生素（antibiotics, Ab）预处理对FMT过程中供体微生物群定植的影响。我们以两种健康小鼠品系为对象开展了FMT临床前研究，以模拟人类受试者之间的个体间FMT。微生物群组成通过高通量16S rDNA扩增子测序进行评估。研究结果显示，FMT前经Ab处理的小鼠，其肠道微生物群丰度显著降低，但与对照组相比，Ab预处理并未提升受体小鼠微生物群与供体小鼠微生物群的整体相似性。然而，供体小鼠中丰度较高的双歧杆菌（Bifidobacterium）及其他多个分类群，在经Ab预处理的受体小鼠中丰度显著升高。综上，广谱抗生素预处理并未提升供体微生物群的整体定植效率，但可改善包括双歧杆菌在内的特定分类群的定植效果。