Ecological landscapes guide the assembly of optimal microbial communities

Author summaryResearch shows that microbial communities comprised of specific species combinations can cure disease, improve agricultural output, or synthesize valuable chemicals. But finding the species combinations that generate high-performing communities is challenging because there are too many species combinations to test exhaustively. So, scientists use heuristic strategies that test only a few species combinations to search for high-performing communities. However, these heuristic strategies often fail to find the best species combinations, and we still do not understand when they fail. Here, we develop a framework to analyze these heuristic strategies, building on the concept of fitness landscapes studied in evolution and computer science. We apply this framework to data from simulated microbial community models to identify biological properties that affect the success of heuristic search strategies, such as the extent to which microbes compete for the same metabolites. Further, we establish statistical measures of the landscape structure that can help estimate search success from preliminary data. We validate our findings using experimental data from communities of soil microbes. Together, our results develop a conceptual framework to analyze and develop heuristic search strategies and identify guiding principles to help scientists choose species and environmental conditions that make finding high-performing microbial communities easier. Assembling optimal microbial communities is key for various applications in biofuel production, agriculture, and human health. Finding the optimal community is challenging because the number of possible communities grows exponentially with the number of species, and so an exhaustive search cannot be performed even for a dozen species. A heuristic search that improves community function by adding or removing one species at a time is more practical, but it is unknown whether this strategy can discover an optimal or nearly optimal community. Using consumer-resource models with and without cross-feeding, we investigate how the efficacy of search depends on the distribution of resources, niche overlap, cross-feeding, and other aspects of community ecology. We show that search efficacy is determined by the ruggedness of the appropriately-defined ecological landscape. We identify specific ruggedness measures that are both predictive of search performance and robust to noise and low sampling density. The feasibility of our approach is demonstrated using experimental data from a soil microbial community. Overall, our results establish the conditions necessary for the success of the heuristic search and provide concrete design principles for building high-performing microbial consortia.