Microbial communities often undergo intricate compositional changes yet also maintain stable coexistence of diverse species. The mechanisms underlying long-term coexistence remain unclear as system-wide studies have been largely limited to engineered communities, ex situ adapted cultures or synthetic assemblies. Here, we show how kefir, a natural milk-fermenting community of prokaryotes (predominantly lactic and acetic acid bacteria) and yeasts (family Saccharomycetaceae), realizes stable coexistence through spatiotemporal orchestration of species and metabolite dynamics. During milk fermentation, kefir grains (a polysaccharide matrix synthesized by kefir microorganisms) grow in mass but remain unchanged in composition. In contrast, the milk is colonized in a sequential manner in which early members open the niche for the followers by making available metabolites such as amino acids and lactate. Through metabolomics, transcriptomics and large-scale mapping of inter-species interactions, we show how microorganisms poorly suited for milk survive in—and even dominate—the community, through metabolic cooperation and uneven partitioning between grain and milk. Overall, our findings reveal how inter-species interactions partitioned in space and time lead to stable coexistence.

微生物群落经常经历复杂的组成变化，但也保持不同物种的稳定共存。长期共存的机制仍不清楚，因为全系统研究主要限于工程群落、异地适应培养物或合成组装体。在这里，我们展示了开菲尔，一种由原核生物（主要是乳酸菌和醋酸菌）和酵母（酵母科）组成的天然牛奶发酵群落，如何通过物种和代谢物动态的时空协调实现稳定共存。在牛奶发酵过程中，开菲尔粒（由开菲尔微生物合成的多糖基质）大量生长，但成分保持不变。相比之下，牛奶以连续的方式定植，其中早期成员通过提供氨基酸和乳酸等可用代谢物为追随者打开利基。通过代谢组学、转录组学和大规模物种间相互作用图谱，我们展示了不适合牛奶的微生物如何通过代谢合作和谷物与牛奶之间的不均匀分配在群落中生存甚至占据主导地位。总的来说，我们的研究结果揭示了在空间和时间上划分的物种间相互作用如何导致稳定共存。