ABSTRACT
Metabolic exchange can mediate beneficial interactions among microbes, helping explain diversity in microbial communities. These interactions are often assumed to involve a fitness cost, prompting questions on how cooperative phenotypes can be stable and withstand the emergence of cheaters. Here we use genome-scale models of metabolism to investigate whether a radically different scenario, the pervasive release of “costless” metabolites (i.e. those that cause no fitness cost to the producing organism), can serve as a prominent mechanism for inter-microbial interactions. By carrying out over 1 million pairwise growth simulations for 14 microbial species in a combinatorial assortment of environmental conditions, we find that there is indeed a large space of metabolites that can be secreted at no cost, which can generate ample cross-feeding opportunities. In addition to providing an atlas of putative costless interdependencies, our modeling also demonstrates that oxygen availability significantly enhances mutualistic interactions by providing more opportunities for metabolic exchange through costless metabolites, resulting in an over-representation of specific ecological network motifs. In addition to helping explain natural diversity, we show how the exchange of costless metabolites can facilitate the engineering of stable synthetic microbial consortia.