Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.
Biosciences Division, Oak Ridge National Laboratorygrid.135519.a, Oak Ridge, Tennessee, USA.
Microbiol Spectr. 2022 Jun 29;10(3):e0106722. doi: 10.1128/spectrum.01067-22. Epub 2022 May 10.
Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing techniques to analyze growth under a range of conditions representing the nutrient environment of the host. We verify that B. thetaiotaomicron fermentation products are sufficient for M. smithii growth and that accumulation of fermentation products alters secretion of metabolites by B. thetaiotaomicron to benefit M. smithii. Studies suggest that B. thetaiotaomicron metabolic efficiency is greater in the absence of fermentation products or in the presence of M. smithii. Under certain conditions, B. thetaiotaomicron and M. smithii form interspecies granules consistent with behavior observed for syntrophic partnerships between microbes in soil or sediment enrichments and anaerobic digesters. Furthermore, when vitamin B, hematin, and hydrogen gas are abundant, coculture growth is greater than the sum of growth observed for monocultures, suggesting that both organisms benefit from a synergistic mutual metabolic relationship. The human gut functions through a complex system of interactions between the host human tissue and the microbes which inhabit it. These diverse interactions are difficult to model or examine under controlled laboratory conditions. We studied the interactions between two dominant human gut microbes, B. thetaiotaomicron and M. smithii, using a seven-component culturing approach that allows the systematic examination of the metabolic complexity of this binary microbial system. By combining high-throughput methods with machine learning techniques, we were able to investigate the interactions between two dominant genera of the gut microbiome in a wide variety of environmental conditions. Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase.
微生物之间的营养相互作用被认为决定了宿主微生物组是健康的还是容易患病的。两种丰富的分类群，革兰氏阴性异养细菌拟杆菌属和产甲烷古菌史密斯甲烷短杆菌，被认为具有协同的代谢关系。这两种生物在人类肠道健康中都起着至关重要的作用；拟杆菌属通过发酵膳食多糖来帮助宿主，而史密斯甲烷短杆菌则消耗发酵的终产物，并被假设可以缓解上游微生物（如拟杆菌属）的反馈抑制。为了研究它们的代谢相互作用，我们定义并优化了一种共培养系统，并使用软件测试技术分析了一系列代表宿主营养环境的条件下的生长情况。我们验证了拟杆菌属发酵产物足以促进史密斯甲烷短杆菌的生长，并且发酵产物的积累改变了拟杆菌属的代谢产物分泌，从而有利于史密斯甲烷短杆菌的生长。研究表明，在没有发酵产物或存在史密斯甲烷短杆菌的情况下，拟杆菌属的代谢效率更高。在某些条件下，拟杆菌属和史密斯甲烷短杆菌形成种间颗粒，这与在土壤或沉积物富集物和厌氧消化器中观察到的微生物之间的共生关系的行为一致。此外，当维生素 B、血红素和氢气丰富时，共培养的生长大于单培养观察到的生长之和，这表明两种生物都受益于协同的相互代谢关系。人类肠道通过宿主组织与栖息其中的微生物之间的复杂系统相互作用来发挥功能。这些多样化的相互作用在受控的实验室条件下很难建模或研究。我们使用一种由七个成分组成的培养方法来研究两种主要的人类肠道微生物，即拟杆菌属和史密斯甲烷短杆菌之间的相互作用，这种方法允许系统地研究这个二元微生物系统的代谢复杂性。通过将高通量方法与机器学习技术相结合，我们能够在各种环境条件下研究肠道微生物组的两个主要属之间的相互作用。我们的方法可以广泛应用于研究微生物相互作用，并可以扩展到评估和管理计算代谢模型。本研究开发的软件工具可作为能源部 KBase 中的用户友好教程使用。
