Center for Genome Science and Systems Biology, Washington University School of Medicine, St Louis, MO 63108, USA.
Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6252-7. doi: 10.1073/pnas.1102938108. Epub 2011 Mar 21.
The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.
人类肠道细菌群落中难以培养的部分仍然定义不明确。在本报告中,我们结合高通量厌氧培养技术与无菌动物养殖和宏基因组学,表明人类粪便微生物组主要由其可培养成员中存在的分类群和预测功能组成。当移植到无菌小鼠中时,完整和培养的群落表现出相似的定植动力学、生物地理分布和对饮食干扰的反应。此外,无菌小鼠可用于塑造这些个性化的培养物集合,以富集适合特定饮食的分类群。我们还证明,来自单个供体的数千个分离株可以在微孔板格式中进行克隆存档和分类映射,以创建个性化的微生物组集合。检索在具有生理或疾病表型的单个供体中共同存在的微生物群落的组成部分,并将它们在无菌小鼠中以各种组合重新组合,应该有助于设计临床前研究,以确定可培养细菌分类群在多大程度上能够传递供体特征或影响宿主生物学。