Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota.
Host Gut Motility Promotes Competitive Exclusion within a Model Intestinal Microbiota.
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DOI：
10.1371/journal.pbio.1002517
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发表时间：
2016-07
期刊：
影响因子：
9.8
通讯作者：
Parthasarathy R
中科院分区：
文献类型：
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作者：
Wiles TJ;Jemielita M;Baker RP;Schlomann BH;Logan SL;Ganz J;Melancon E;Eisen JS;Guillemin K;Parthasarathy R
肠道微生物群是一个复杂的微生物群落，能够影响宿主健康和发育的重要方面。利用这种“微生物器官”用于生物医学应用需要澄清宿主和细菌因素单独或联合作用于特定谱系稳定性的程度。为了解决这个问题，我们结合细菌学操作和光片荧光显微镜来监测脊椎动物肠道内定义的两种微生物群的动态。我们观察到，每个种群和肠道环境之间的相互作用产生不同的时空模式。结果，一个物种占主导地位，而另一个物种的丰度突然下降，这与随机数学模型非常吻合。建模显示，直接的细菌竞争只能部分解释观察到的现象，这表明宿主因素在塑造社区中也很重要。我们假设宿主决定因素是肠道动力，并通过测量由于ret基因突变导致肠神经系统功能障碍的宿主中的定植来测试这种机制，ret基因突变在人类中与称为先天性巨结肠症的肠道动力障碍相关。在突变宿主中，我们发现肠道运动减少，证实了我们的假设，两种细菌物种的共存。这项研究提供的证据表明，宿主介导的空间结构和群落的随机扰动可以驱动肠道内的细菌种群动态，并且通过展示肠神经系统影响微生物群的能力，揭示了肠道宿主-微生物界面的新方面。最终，这些发现表明，针对肠道生态系统的治疗策略应考虑肠道环境的动态物理性质。模型肠道微生物群的实时成像显示，肠道神经功能和代谢，结合微生物群落的空间结构，可以驱动细菌物种之间的竞争。数百种微生物在人类和其他动物的肠道内茁壮成长，它们可以深刻地影响宿主的健康。影响肠道微生物群组成的因素尚不清楚，但确定它们是开发与微生物失衡相关疾病治疗方法的重要一步。目前的实验方法很难捕捉肠道内微生物相互作用的空间和时间方面，但这些特征可能会为决定微生物群组成的因素提供线索。为了解决这个问题，我们使用了最先进的实时成像技术来跟踪脊椎动物宿主模型斑马鱼肠道内的两种细菌。我们观察到每个种群的空间组织和肠道蠕动活动之间存在显著不同的相互作用。结果，一个物种占主导地位，而另一个物种的丰度突然下降，其动态由随机数学模型预测。从这项工作中，我们得出结论，土著微生物群落的组成可能，在一定程度上，是由物理肠道环境和细菌种群的空间结构的组合。
The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this “microbial organ” for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this issue, we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within a vertebrate gut. We observed that the interplay between each population and the gut environment produces distinct spatiotemporal patterns. As a consequence, one species dominates while the other experiences sudden drops in abundance that are well fit by a stochastic mathematical model. Modeling revealed that direct bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to a mutation in the ret locus, which in humans is associated with the intestinal motility disorder known as Hirschsprung disease. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities can drive bacterial population dynamics within the gut, and it reveals a new facet of the intestinal host–microbe interface by demonstrating the capacity of the enteric nervous system to influence the microbiota. Ultimately, these findings suggest that therapeutic strategies targeting the intestinal ecosystem should consider the dynamic physical nature of the gut environment. Live imaging of a model intestinal microbiota reveals that enteric neural function and peristalsis, combined with the spatial structure of microbial communities, can drive competition between bacterial species. Hundreds of microbial species thrive within the gut of humans and other animals, where they can influence the health of their host in profound ways. The factors that shape the composition of the resident gut microbiota are not well understood, but identifying them represents an important step toward developing treatments for diseases associated with microbial imbalances. Current experimental approaches poorly capture spatial and temporal aspects of microbial interactions within the gut, and yet these features may hold clues to what determines the composition of the microbiota. To address this issue, we used state-of-the-art live imaging to track two bacterial species within the intestine of a model vertebrate host, the zebrafish. We observed strikingly different interplay between the spatial organization of each population and the intestine’s peristaltic activity. As a result, one species dominates while the other experiences sudden drops in abundance, the dynamics of which are predicted by a stochastic mathematical model. From this work, we conclude that the composition of indigenous microbial communities may, in part, be shaped by a combination of the physical intestinal environment and the spatial structure of bacterial populations.