Institute of Molecular Systems Biology, D-BIOL, ETH Zurich, Zurich, Switzerland.
Systems Biology Graduate School, Zurich, Switzerland.
mSystems. 2022 Apr 26;7(2):e0148421. doi: 10.1128/msystems.01484-21. Epub 2022 Mar 31.
The complex interactions between the gut microbiome and host or pathogen colonization resistance cannot be understood solely from community composition. Missing are causal relationships, such as metabolic interactions among species, to better understand what shapes the microbiome. Here, we focused on metabolic niches generated and occupied by the Oligo-Mouse-Microbiota (OMM) consortium, a synthetic community composed of 12 members that is increasingly used as a model for the mouse gut microbiome. Combining monocultures and spent medium experiments with untargeted metabolomics revealed broad metabolic diversity in the consortium, constituting a dense cross-feeding network with more than 100 pairwise interactions. Quantitative analysis of the cross-feeding network revealed distinct C and N food webs, highlighting the two members Bacteroides caecimuris and Muribaculum intestinale as primary suppliers of carbon and a more diverse group as nitrogen providers. Cross-fed metabolites were mainly carboxylic acids, amino acids, and the so far not reported nucleobases. In particular, the dicarboxylic acids malate and fumarate provided a strong physiological benefit to consumers, presumably used in anaerobic respiration. Isotopic tracer experiments validated the fate of a subset of cross-fed metabolites, such as the conversion of the most abundant cross-fed compound succinate to butyrate. Thus, we show that this consortium is tailored to produce the anti-inflammatory metabolite butyrate. Overall, we provide evidence for metabolic niches generated and occupied by OMM members that lays a metabolic foundation to facilitate an understanding of the more complex behavior of this consortium in the mouse gut. This article maps out the cross-feeding network among 10 members of a synthetic consortium that is increasingly used as the model mouse gut microbiota. Combining metabolomics with cultivations, two dense networks of carbon and nitrogen exchange are described. The vast majority of the ∼100 interactions are synergistic in nature, in several cases providing distinct physiological benefits to the recipient species. These networks lay the groundwork toward understanding gut community dynamics and host-gut microbe interactions.
肠道微生物组与宿主或病原体定植抗性之间的复杂相互作用不能仅从群落组成来理解。缺少的是物种之间的代谢相互作用等因果关系，无法更好地了解是什么塑造了微生物组。在这里，我们专注于由寡聚鼠微生物群（OMM）联合体产生和占据的代谢生态位，该联合体由 12 个成员组成，越来越多地被用作小鼠肠道微生物组的模型。结合单培养物和消耗培养基实验与非靶向代谢组学揭示了联合体中的广泛代谢多样性，构成了一个具有 100 多个对相互作用的密集交叉喂养网络。对交叉喂养网络的定量分析揭示了明显的 C 和 N 食物网，突出了两个成员 Bacteroides caecimuris 和 Muribaculum intestinale 作为碳的主要供应者，以及更多样化的群体作为氮供应者。交叉喂养的代谢物主要是羧酸、氨基酸和迄今为止未报道的核碱基。特别是，二羧酸苹果酸和富马酸为消费者提供了很强的生理益处，推测它们用于厌氧呼吸。同位素示踪实验验证了一部分交叉喂养代谢物的命运，例如最丰富的交叉喂养化合物琥珀酸转化为丁酸。因此，我们表明该联合体专门生产抗炎代谢物丁酸。总的来说，我们为 OMM 成员产生和占据的代谢生态位提供了证据，为理解该联合体在小鼠肠道中的更复杂行为奠定了代谢基础。 本文绘制了一个合成联合体的 10 个成员之间的交叉喂养网络，该联合体越来越多地被用作模型小鼠肠道微生物群。结合代谢组学和培养物，描述了两个密集的碳和氮交换网络。在大多数情况下，大约 100 个相互作用中的绝大多数是协同的，在几种情况下为受体物种提供了明显的生理益处。这些网络为理解肠道群落动态和宿主-肠道微生物相互作用奠定了基础。
