Institute of Molecular Biology, University of Oregon, Eugene, Oregon; Department of Physics and Materials Science Institute, University of Oregon, Eugene, Oregon.
Institute of Molecular Biology, University of Oregon, Eugene, Oregon.
Biophys J. 2018 Dec 4;115(11):2271-2277. doi: 10.1016/j.bpj.2018.10.017. Epub 2018 Oct 30.
Are there general biophysical relationships governing the spatial organization of the gut microbiome? Despite growing realization that spatial structure is important for population stability, interbacterial competition, and host functions, it is unclear in any animal gut whether such structure is subject to predictive, unifying rules or if it results from contextual, species-specific behaviors. To explore this, we used light sheet fluorescence microscopy to conduct a high-resolution comparative study of bacterial distribution patterns throughout the entire intestinal volume of live, larval zebrafish. Fluorescently tagged strains of seven bacterial symbionts, representing six different species native to zebrafish, were each separately monoassociated with animals that had been raised initially germ-free. The strains showed large differences in both cohesion-the degree to which they auto-aggregate-and spatial distribution. We uncovered a striking correlation between each strain's mean position and its cohesion, whether quantified as the fraction of cells existing as planktonic individuals, the average aggregate size, or the total number of aggregates. Moreover, these correlations held within species as well; aggregates of different sizes localized as predicted from the pan-species observations. Together, our findings indicate that bacteria within the zebrafish intestine are subject to generic processes that organize populations by their cohesive properties. The likely drivers of this relationship-peristaltic fluid flow, tubular anatomy, and bacterial growth and aggregation kinetics-are common throughout animals. We therefore suggest that the framework introduced here of biophysical links between bacterial cohesion and spatial organization should be useful for directing explorations in other host-microbe systems, formulating detailed models that can quantitatively map onto experimental data, and developing new tools that manipulate cohesion to engineer microbiome function.
肠道微生物组的空间组织是否存在普遍的生物物理关系？尽管人们越来越认识到空间结构对于种群稳定性、细菌间竞争和宿主功能很重要，但在任何动物的肠道中，尚不清楚这种结构是否受到可预测的、统一的规则支配，还是由特定于上下文的、物种特异性的行为所导致。为了探索这个问题，我们使用光片荧光显微镜对活体斑马鱼幼虫整个肠道体积中的细菌分布模式进行了高分辨率的比较研究。七种细菌共生体的荧光标记菌株，代表了六种原产于斑马鱼的不同物种，分别与最初无菌饲养的动物单关联。这些菌株在凝聚性——它们自动聚集的程度和空间分布上都表现出很大的差异。我们发现每个菌株的平均位置与其凝聚性之间存在惊人的相关性，无论是用浮游个体的细胞分数、平均聚集大小还是总聚集数来量化。此外，这些相关性在物种内也成立；不同大小的聚集体在种间观察到的位置。总之，我们的研究结果表明，斑马鱼肠道内的细菌受到将种群按其凝聚特性进行组织的通用过程的影响。这种关系的可能驱动力——蠕动流体流动、管状解剖结构以及细菌生长和聚集动力学——在动物中普遍存在。因此，我们建议将细菌凝聚性和空间组织之间的生物物理联系框架引入到其他宿主-微生物系统的探索中，构建可以定量映射到实验数据的详细模型，并开发新的工具来操纵凝聚性以设计微生物组功能。
