Metabolic Modeling Elucidates the Transactions in the Rumen Microbiome and the Shifts Upon Virome Interactions
Metabolic Modeling Elucidates the Transactions in the Rumen Microbiome and the Shifts Upon Virome Interactions
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DOI：
10.3389/fmicb.2019.02412
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发表时间：
2019-10-22
影响因子：
5.2
通讯作者：
Saha, Rajib
中科院分区：
文献类型：
--
作者：
Islam, Mohammad Mazharul;Fernando, Samodha C.;Saha, Rajib
牛瘤胃内复杂的微生物生态系统对宿主的营养、健康和环境影响起着至关重要的作用。然而，对系统内功能实体之间的相互作用知之甚少，这些相互作用决定了群落结构和功能动态以及宿主生理。随着高通量测序和数学建模的进步，计算机基因组级代谢分析有望扩大我们对社区代谢相互作用的理解。为了了解瘤胃内微生物物种与噬菌体之间的相互作用，利用瘤胃微生物组的关键成员（拟杆菌门、厚壁菌门和古细菌）及其相关的病毒噬菌体，采用了基因组尺度的代谢建模方法。利用多层次的数学框架将个体微生物宿主模型整合到群落模型中。采用了一种精细的启发式计算程序来预测先前未知的相互作用，包括脂肪酸、维生素、辅酶、氨基酸和糖在群落成员之间的转移。虽然其中一些相互作用可以通过可用的多组学数据集推断出来，但我们提出的方法提供了对相互作用发生的原因以及这些相互作用如何影响复杂微生物生态系统动力学的系统理解。为了阐明病毒组在微生物组中的功能作用，使用局部比对搜索来鉴定与宿主相关的病毒的代谢功能。这些功能的结合证明了病毒辅助代谢基因在缓解微生物宿主代谢瓶颈和补充种间相互作用方面的作用。最后，通过对不同生物显著的群落适应度标准的比较统计分析，确定了群落成员代谢能力的通量空间和稳健性的变化。我们对瘤胃微生物组三个成员之间代谢物交换的阐明，显示了它们的基因组差异和与病毒株的相互作用如何形成高度复杂的代谢相互作用，并解释了这种跨王国的相互作用如何导致群落的代谢和组成变化，并影响反刍动物的健康、营养和病理生理。
The complex microbial ecosystem within the bovine rumen plays a crucial role in host nutrition, health, and environmental impact. However, little is known about the interactions between the functional entities within the system, which dictates the community structure and functional dynamics and host physiology. With the advancements in high-throughput sequencing and mathematical modeling, in silico genome-scale metabolic analysis promises to expand our understanding of the metabolic interplay in the community. In an attempt to understand the interactions between microbial species and the phages inside rumen, a genome-scale metabolic modeling approach was utilized by using key members in the rumen microbiome (a bacteroidete, a firmicute, and an archaeon) and the viral phages associated with them. Individualmicrobial hostmodels were integrated into a communitymodel usingmulti-level mathematical frameworks. An elaborate and heuristics-based computational procedure was employed to predict previously unknown interactions involving the transfer of fatty acids, vitamins, coenzymes, amino acids, and sugars among the community members. While some of these interactions could be inferred by the available multi-omic datasets, our proposed method provides a systemic understanding of why the interactions occur and how these affect the dynamics in a complex microbial ecosystem. To elucidate the functional role of the virome on the microbiome, local alignment search was used to identify the metabolic functions of the viruses associated with the hosts. The incorporation of these functions demonstrated the role of viral auxiliary metabolic genes in relaxing the metabolic bottlenecks in the microbial hosts and complementing the inter-species interactions. Finally, a comparative statistical analysis of different biologically significant community fitness criteria identified the variation in flux space and robustness of metabolic capacities of the community members. Our elucidation of metabolite exchange among the threemembers of the rumenmicrobiome shows how their genomic differences and interactions with the viral strains shape up a highly sophisticated metabolic interplay and explains how such interactions across kingdoms can cause metabolic and compositional shifts in the community and affect the health, nutrition, and pathophysiology of the ruminant animal.