Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA; Immunology Institute and Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Immunity. 2014 Jun 19;40(6):815-23. doi: 10.1016/j.immuni.2014.05.012.
The gut microbiota codevelops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community and immune system coregulation and to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed.
肠道微生物群与免疫系统从出生开始就共同发育。从微生物群中挖掘负责塑造先天和适应性免疫系统结构和动态运作的细菌菌株是一个艰巨的组合问题，但需要克服这个问题，以推进对微生物群落和免疫系统协同调控的机制理解，并开发促进健康的新的诊断和治疗方法。在这里，我们讨论了一种可扩展的、偏差较小的方法，用于识别影响免疫功能的复杂微生物群落中的效应菌株。该方法首先从代表供体微生物群落的克隆排列的测序菌株集合开始。如果该集合传递表型，则通过在单独饲养的无菌动物中测试具有重叠成员的随机生成的子集来鉴定效应菌株。然后可以对效应菌株-宿主相互作用进行详细的机制研究。
