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Environments that Induce Synthetic Microbial
Ecosystems
1 ` 1,2
Niels Klitgord , Daniel Segre *
1 Bioinformatics Program, Boston University, Boston, Massachusetts, United States of America, 2 Department of Biology and Department of Biomedical Engineering,
Boston University, Boston, Massachusetts, United States of America
Abstract
Interactions between microbial species are sometimes mediated by the exchange of small molecules, secreted by one
species and metabolized by another. Both one-way (commensal) and two-way (mutualistic) interactions may contribute to
complex networks of interdependencies. Understanding these interactions constitutes an open challenge in microbial
ecology, with applications ranging from the human microbiome to environmental sustainability. In parallel to natural
communities, it is possible to explore interactions in artificial microbial ecosystems, e.g. pairs of genetically engineered
mutualistic strains. Here we computationally generate artificial microbial ecosystems without re-engineering the microbes
themselves, but rather by predicting their growth on appropriately designed media. We use genome-scale stoichiometric
models of metabolism to identify media that can sustain growth for a pair of species, but fail to do so for one or both
individual species, thereby inducing putative symbiotic interactions. We first tested our approach on two previously studied
mutualistic pairs, and on a pair of highly curated model organisms, showing that our algorithms successfully recapitulate
known interactions, robustly predict new ones, and provide novel insight on exchanged molecules. We then applied our
method to all possible pairs of seven microbial species, and found that it is always possible to identify putative media that
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