The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model‐guided framework to predict higher‐dimensional consortia from time‐resolved measurements of lower‐order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi‐species community dynamics, as opposed to higher‐order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history‐dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human‐associated intestinal species and illuminated design principles of microbial communities.

中文翻译：

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合成人肠道微生物组群落中微生物相互作用的解密

支配人类肠道菌群的组装和稳定性的生态力仍未得到解决。我们开发了一个可推广的模型指导框架，以通过对低阶组合的时间分辨测量来预测高维财团。该方法用于破译不同人类肠道微生物组合成社区中的微生物相互作用。我们表明，成对互动是多物种社区动态的主要驱动力，而不是更高层次的互动。推断的生态网络表现出很大比例的负面和频繁的正面互动。在网络中发现了生态驱动力和反应灵敏的接受物种。我们的模型表明，普遍存在的正负互动拓扑结构通过实施负反馈回路来平衡单物种适应性水平之间的差异，从而实现了稳健的共存。我们表明，负面的相互作用可能会产生初始物种比例的历史依赖响应，而这种响应通常并非源自双稳态。细胞外代谢物的测量阐明了单物种的代谢能力和微生物相互作用的潜在分子基础。总之，这些方法定义了人类主要肠道物种的生态作用，并阐明了微生物群落的设计原理。我们表明，负面的相互作用可能会产生初始物种比例的历史依赖响应，而这种响应通常并非源自双稳态。细胞外代谢物的测量阐明了单物种的代谢能力和微生物相互作用的潜在分子基础。总之，这些方法定义了人类主要肠道物种的生态作用，并阐明了微生物群落的设计原理。我们表明，负面的相互作用可能会产生初始物种比例的历史依赖响应，而这种响应通常并非源自双稳态。细胞外代谢物的测量阐明了单物种的代谢能力和微生物相互作用的潜在分子基础。总之，这些方法定义了人类主要肠道物种的生态作用，并阐明了微生物群落的设计原理。