Evidence for a multi-level trophic organization of the human gut microbiome

The human gut microbiome is a complex ecosystem, in which hundreds of microbial species and metabolites coexist, in part due to an extensive network of cross-feeding interactions. However, both the large-scale trophic organization of this ecosystem, and its effects on the underlying metabolic flow, remain unexplored. Here, using a simplified model, we provide quantitative support for a multi-level trophic organization of the human gut microbiome, where microbes consume and secrete metabolites in multiple iterative steps. Using a manually-curated set of metabolic interactions between microbes, our model suggests about four trophic levels, each characterized by a high level-to-level metabolic transfer of byproducts. It also quantitatively predicts the typical metabolic environment of the gut (fecal metabolome) in approximate agreement with the real data. To understand the consequences of this trophic organization, we quantify the metabolic flow and biomass distribution, and explore patterns of microbial and metabolic diversity in different levels. The hierarchical trophic organization suggested by our model can help mechanistically establish causal links between the abundances of microbes and metabolites in the human gut.

人类肠道微生物组（human gut microbiome）是一类复杂的生态系统，数百种微生物物种与代谢物在此共存，这在一定程度上源于庞大的交叉摄食相互作用（cross-feeding interactions）网络。然而，该生态系统的大规模营养层级组织（trophic organization）及其对底层代谢流的影响，至今仍未得到充分探索。本研究通过构建简化模型，为人类肠道微生物组的多层营养层级组织提供了定量支撑：在该结构中，微生物通过多轮迭代步骤完成代谢物的摄取与分泌。基于一套经人工整理筛选的微生物代谢相互作用数据集，我们的模型显示该系统约存在四个营养级，每个营养级均以显著的跨营养级代谢副产物转移为核心特征。该模型还可定量预测肠道典型代谢环境——粪便代谢组（fecal metabolome），其预测结果与真实实验数据大体吻合。为明晰该营养层级组织的生物学效应，本研究对代谢流与生物量分布开展了定量分析，并探究了不同营养级的微生物与代谢多样性模式。本模型提出的层级式营养组织，有助于从机制层面建立人类肠道内微生物丰度与代谢物丰度之间的因果关联。