Synthetic assembly of a functional rumen microbiome by exometabolome supplementation

Microbes transform their local environment by releasing exometabolites that promote or inhibit growth, thereby opening and closing niches for other microorganisms. Yet, the extent to which exometabolites can act as levers to control community assembly in complex environments like mammalian guts, remains unclear. Here we show that exometabolites could be used to reproduce, in vitro, the natural successional dynamics of community assembly that takes place in the cows rumen. Exometabolites transiently consumed, such as pregnane steroids, ceramides and triterpenoids, are needed to direct the assembly process for specific microbes that are abundant and prevalent during the animals life to become metabolically active. These metabolites make the assembly process robust to compositional variation, as seen in the deterministic convergence in composition of independent microcosms. Overall, we show in this work that metabolite supplementation can be an effective strategy for microbiome control.