论文标题

基于代谢模型的益生菌设计的生态模型

Metabolic Model-based Ecological Modeling for Probiotic Design

论文作者

Brunner, James D., Chia, Nicholas

论文摘要

人类肠道中的微生物群落组成对人类健康具有深远的影响。这一观察结果导致了微生物组疗法的广泛使用,包括旨在改变微生物组组成的``益生菌''治疗方法。尽管有很大的希望和商业兴趣,这些因素,导致微生物组成功治疗的成功或失败的因素仍不清楚。我们调查了对插入物质的生物互动的研究。使用具有广义资源分配约束的成对代谢模型,在Agora数据库中使用818个物种之间的相互作用网络广义的Lotka-volterra模型具有强大的能力,可以预测特定的入侵者或益生菌是否会成功地植入个人的微生物组中,我们表明该模型的机械性质有助于揭示哪些微生物相互作用可能潜在的驱动驱动。

The microbial community composition in the human gut has a profound effect on human health. This observation has lead to extensive use of microbiome therapies, including over-the-counter ``probiotic" treatments intended to alter the composition of the microbiome. Despite so much promise and commercial interest, the factors that contribute to the success or failure of microbiome-targeted treatments remain unclear. We investigate the biotic interactions that lead to successful engraftment of a novel bacterial strain introduced to the microbiome as in probiotic treatments. We use pairwise genome-scale metabolic modeling with a generalized resource allocation constraint to build a network of interactions between 818 species with well developed models available in the AGORA database. We create induced sub-graphs using the taxa present in samples from three experimental engraftment studies and assess the likelihood of invader engraftment based on network structure. To do so, we use a set of dynamical models designed to reflect connect network topology to growth dynamics. We show that a generalized Lotka-Volterra model has strong ability to predict if a particular invader or probiotic will successfully engraft into an individual's microbiome. Furthermore, we show that the mechanistic nature of the model is useful for revealing which microbe-microbe interactions potentially drive engraftment.

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