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一个用于研究结肠微生物区系生物地理学关键驱动因素的数学模型。

A mathematical model to investigate the key drivers of the biogeography of the colon microbiota.

机构信息

MaIAGE, INRA, Paris-Saclay University, Jouy-en-Josas, France.

Univ Lyon, CNRS, Université Claude Bernard Lyon 1, UMR5208, Institut Camille Jordan, F-69622 Villeurbanne, France.

出版信息

J Theor Biol. 2019 Feb 7;462:552-581. doi: 10.1016/j.jtbi.2018.12.009. Epub 2018 Dec 7.

DOI:10.1016/j.jtbi.2018.12.009
PMID:30529486
Abstract

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest: spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities.

摘要

肠道微生物群主要位于结肠,通过与大肠上皮细胞进行复杂的对话,参与宿主健康和幸福的重要调节过程。微生物种群的失衡,称为菌群失调,与几种病理状态有关,这强调了了解肠道细菌生态的重要性。在微生物群的生态驱动因素中,结肠的空间结构特别有趣:时空机制可以导致细菌种群之间的空间相互作用以及影响结肠整体定植的环境小生境的构成。在本研究中,我们基于涉及纤维降解的微生物种群的群体动力学模型与腔内容物的流体动力学模型的明确耦合,引入了一个肠道微生物群的数学模型,在其流体环境中。该建模框架用于研究微生物群空间结构的主要驱动因素,特别是重点关注膳食纤维流入、上皮运动、微生物主动游动和消化道中的粘度梯度。我们发现 1)粘度梯度允许在粘液层附近创建有利的小生境;2)微生物在径向方向的非常低的主动游动足以促进细菌生长,这为结肠中的微生物运动提供了新的视角;3)膳食纤维是远端肠道中微生物群空间结构的主要驱动因素,而上皮运动对于近端结肠的定植占主导地位;在横结肠中,纤维水平和趋化性对微生物群落的分布有最强的影响。

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