Vancomycin resistant Enterococcus faecium (VREfm) is an emerging antibiotic resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenerricutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone, and to subsequent VREfm challenge. Using neural networking approaches to find co-occurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition towards a pre-antibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem, and the progression of the microbiome in response to colonisation with VREfm. Our results offer insights towards identifying potential non-antibiotic alternatives to eliminate VREfm through metabolic re-engineering to preferentially select for Bacteroides. Importance: This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

中文翻译：

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与万古霉素耐药的粪肠球菌定殖后微生物代谢产物关联与反弹鼠肠道微生物组

耐万古霉素的粪肠球菌（VREfm）是一种新兴的耐抗生素病原体。菌株水平的研究开始揭示VREfm用来定居人肠区域的分子机制。然而，共生细菌在VREfm移殖过程中的作用，尤其是在抗生素治疗后，仍是未知之数。我们在小鼠模型系统中使用了扩增子16S rRNA基因测序和代谢组学，试图研究在VREfm定居过程中肠道微生物组的功能。在使用头孢曲松的预处理以及随后的VREfm攻击中，都检测到肠道微生物群落组成内的拟杆菌和特里特虫之间的一级分类学变化。使用神经网络方法查找细菌和代谢物的共现谱，我们在VREfm定植期间和之后检测到了与丁酸相关的关键代谢组特征。这些代谢物特征与拟杆菌属有关，表明已向抗生素前纯天然微生物组过渡。这项研究显示了抗生素对肠道生态系统的影响以及微生物组对VREfm定植的反应。我们的结果为寻找潜在的非抗生素替代品提供了见识，这些替代品可通过代谢改造来优先选择拟杆菌来消除VREfm。重要性：这项研究证明了将细菌组成图谱与代谢组学联系起来以发现共生肠道细菌与特定病原体之间相互作用的重要性和力量。这项研究的知识将为肠道微生物组工程策略提供参考，