ABSTRACTTo alter microbial community composition for therapeutic purposes, an accurate and reliable modeling framework capable of predicting microbial community outcomes is required. Lotka-Volterra (LV) equations have been utilized to describe a breadth of microbial communities, yet, the conditions in which this modeling framework is successful remain unclear. Here, we propose that a set of simplein vitroexperiments—growing each member in cell-free spent medium obtained from other members—can be used as a test to decide whether an LV model is appropriate for describing microbial interactions of interest. We show that for LV to be a good candidate, the ratio of growth rate to carrying capacity of each isolate when grown in the cell-free spent media of other isolates should remain constant. Using anin vitrocommunity of human nasal bacteria as a tractable system, we find that LV can be a good approximation when the environment is low-nutrient (i.e., when growth is limited by the availability of nutrients) and complex (i.e., when multiple resources, rather than a few, determine growth). These findings can help clarify the range of applicability of LV models and reveal when a more complex model may be necessary for predictive modeling of microbial communities.IMPORTANCEAlthough mathematical modeling can be a powerful tool to draw useful insights in microbial ecology, it is crucial to know when a simplified model adequately represents the interactions of interest. Here, we take advantage of bacterial isolates from the human nasal passages as a tractable model system and conclude that the commonly used Lotka-Volterra model can represent interactions among microbes well when the environment is complex (with many interaction mediators) and low-nutrient. Our work highlights the importance of considering both realism and simplicity when choosing a model to represent microbial interactions.