Department of Systems Biology, Columbia University Medical Center, New York, NY, USA.
Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, NY, USA.
Nat Biotechnol. 2019 Aug;37(8):877-883. doi: 10.1038/s41587-019-0183-2. Epub 2019 Jul 22.
Spatial structuring is important for the maintenance of natural ecological systems. Many microbial communities, including the gut microbiome, display intricate spatial organization. Mapping the biogeography of bacteria can shed light on interactions that underlie community functions, but existing methods cannot accommodate the hundreds of species that are found in natural microbiomes. Here we describe metagenomic plot sampling by sequencing (MaPS-seq), a culture-independent method to characterize the spatial organization of a microbiome at micrometer-scale resolution. Intact microbiome samples are immobilized in a gel matrix and cryofractured into particles. Neighboring microbial taxa in the particles are then identified by droplet-based encapsulation, barcoded 16S rRNA amplification and deep sequencing. Analysis of three regions of the mouse intestine revealed heterogeneous microbial distributions with positive and negative co-associations between specific taxa. We identified robust associations between Bacteroidales taxa in all gut compartments and showed that phylogenetically clustered local regions of bacteria were associated with a dietary perturbation. Spatial metagenomics could be used to study microbial biogeography in complex habitats.
空间结构对于维持自然生态系统至关重要。许多微生物群落,包括肠道微生物群,表现出复杂的空间组织。绘制细菌的生物地理学图谱可以揭示潜在的群落功能相互作用,但现有的方法无法容纳天然微生物群落中存在的数百种物种。在这里,我们描述了通过测序进行的宏基因组图谱采样 (MaPS-seq),这是一种在无需培养的情况下以微米级分辨率描述微生物组空间组织的方法。完整的微生物组样本被固定在凝胶基质中,并冷冻断裂成颗粒。然后通过基于液滴的封装、带有条形码的 16S rRNA 扩增和深度测序来鉴定颗粒中的邻近微生物分类群。对小鼠肠道的三个区域进行分析显示,微生物的分布具有异质性,特定分类群之间存在正相关和负相关。我们在所有肠道隔间中发现了拟杆菌门分类群之间的稳健关联,并表明细菌的系统发育聚类局部区域与饮食干扰有关。空间宏基因组学可用于研究复杂生境中的微生物生物地理学。