肠道微生物群落演替的数学建模。
Mathematical modeling of primary succession of murine intestinal microbiota.
机构信息
Department of Microbiology and Immunology and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
出版信息
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):439-44. doi: 10.1073/pnas.1311322111. Epub 2013 Dec 23.
Understanding the nature of interpopulation interactions in host-associated microbial communities is critical to understanding gut colonization, responses to perturbations, and transitions between health and disease. Characterizing these interactions is complicated by the complexity of these communities and the observation that even if populations can be cultured, their in vitro and in vivo phenotypes differ significantly. Dynamic models are the cornerstone of computational systems biology and a key objective of computational systems biologists is the reconstruction of biological networks (i.e., network inference) from high-throughput data. When such computational models reflect biology, they provide an opportunity to generate testable hypotheses as well as to perform experiments that are impractical or not feasible in vivo or in vitro. We modeled time-series data for murine microbial communities using statistical approaches and systems of ordinary differential equations. To obtain the dense time-series data, we sequenced the 16S ribosomal RNA (rRNA) gene from DNA isolated from the fecal material of germfree mice colonized with cecal contents of conventionally raised animals. The modeling results suggested a lack of mutualistic interactions within the community. Among the members of the Bacteroidetes, there was evidence for closely related pairs of populations to exhibit parasitic interactions. Among the Firmicutes, the interactions were all competitive. These results suggest future animal and in silico experiments. Our modeling approach can be applied to other systems to provide a greater understanding of the dynamics of communities associated with health and disease.
理解宿主相关微生物群落中种群间相互作用的性质对于理解肠道定植、对扰动的反应以及健康与疾病之间的转变至关重要。这些相互作用的特征很复杂,因为这些群落很复杂,而且即使可以培养种群,它们的体外和体内表型也有很大差异。动态模型是计算系统生物学的基石,计算系统生物学家的一个主要目标是从高通量数据中重建生物网络(即网络推断)。当这些计算模型反映生物学时,它们提供了一个机会,可以生成可测试的假设,并进行在体内或体外不切实际或不可行的实验。我们使用统计方法和常微分方程组对鼠类微生物群落的时间序列数据进行了建模。为了获得密集的时间序列数据,我们从无菌小鼠的粪便中提取 DNA,对其 16S 核糖体 RNA(rRNA)基因进行测序,这些无菌小鼠定植了常规饲养动物的盲肠内容物。建模结果表明群落内缺乏互利相互作用。在拟杆菌门的成员中,有证据表明密切相关的种群对表现出寄生相互作用。在厚壁菌门中,相互作用都是竞争性的。这些结果表明未来需要进行动物实验和计算机实验。我们的建模方法可以应用于其他系统,以更深入地了解与健康和疾病相关的群落动态。