Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Gut Microbes. 2023 Jan-Dec;15(1):2229944. doi: 10.1080/19490976.2023.2229944.
Fecal microbiota transplantation (FMT) is used routinely to treat recurrent infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed adhesion and pilus gene expression of long-term colonizing strains from FMT donors as well as colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by expression of colonization factors and boosting endogenous gut microbiota.
粪便微生物群移植(FMT)常用于治疗复发性感染(rCDI),并被研究用于治疗与肠道微生物群改变相关的多种疾病。宏基因组分析表明,供体细菌对受者的定植可能与良好的临床结果相关。双歧杆菌是与健康相关的丰富肠道共生菌。我们之前已经证明,在 FMT 中转移的菌株可以长期定植受者,至少一年,并通过培养回收这些菌株。本研究旨在研究 FMT 供体中长期定植的双歧杆菌的粘附和菌毛基因表达,以及定植和改善抗生素诱导的微生物群失调的能力。RNA-Seq 差异基因表达分析显示,强粘附菌株 DY_pv11 和 DX_pv23 分别表达紧密粘附和依赖于天冬氨酸蛋白酶的菌毛基因。选择两个菌株,粘附的 DX_pv23 和粘附能力差的 DX_pv18,以研究在 C57BL/6 小鼠模型中的定植和恢复抗生素扰乱的微生物群的能力。DX_pv23 以与作为参考的 BB-12 相似的速率短暂定植小鼠。尽管没有任何三种菌株观察到长期定植,但 16S rRNA 基因谱分析表明,DX_pv23 的口服给药显著增强了对受抗生素干扰的微生物群恢复到原始状态的效果,优于其他菌株。研究结果表明,来自 FMT 供体的选定菌株,如本研究中的 DX_pv23,通过表达定植因子和促进内源性肠道微生物群,可能具有治疗潜力。