Microbes release lower-value metabolites at higher rates

Microbial interactions are shaped by the exchange of metabolites, ranging from intermediates in central carbon metabolism to amino acids, vitamins and fermentation by-products1. Yet, the underlying reasons for metabolite release, and the mechanisms and factors influencing release rates are not well understood. Here, using a combination of computational and experimental approaches on seven different microbes we show that release rates are negatively correlated with the value of metabolites, and that this relationship explains more variability in release rates than other frequently associated factors. By measuring metabolite release from 66 E. coli mutants lacking individual metabolite-transport genes, we find that transporters both cause and counteract net metabolite release. These findings show that metabolite release constitutes a fitness cost that microbes have evolved to reduce and reveal the underlying mechanism. This new conceptual explanation for metabolite release reshapes our understanding of how microbial interactions emerge and persist.