misosoup: A metabolic modeling tool for identifying minimal microbial communities reveals pervasive cross–feeding–driven niche expansion

Microbial survival and function often depend on metabolic interactions within communities. Therefore, a central question to disentangle microbial organization is what minimal groups of species are able to thrive in a given medium –referred to as "minimal communities". Answering this question is essential for understanding microbial distribution, enhancing laboratory cultivation, or designing synthetic consortia. Here, we introduce misosoup, a Python package for identifying minimal communities (MInimal Supplying cOmmunity Search). Through genome–scale constraint–based metabolic modeling, misosoup enables the systematic identification of communities that support microbial growth in environments where individual species fail to survive alone. We validate misosoup against experimentally verified minimal communities, demonstrating its ability to predict known cooperative interactions. Applying misosoup to a set of 60 marine microbes, we observe widespread metabolic niche expansion, with approximately 66% of species capable of colonizing more environments in communities than in isolation. Our results highlight the frequent role of metabolic cross-feeding in niche expansion, whereby certain species depend on bidirectional exchange to utilize available resources. The detailed outputs provided by misosoup facilitate research on key questions such as the identification of functional groups. By efficiently identifying minimal communities and elucidating mechanisms underlying species interactions, misosoup provides a powerful tool for microbial ecology and community design, with potential applications in both research and biotechnological innovation.