Significance Quantitatively understanding and predicting spatiotemporal dynamics of microbiota is imperative for development of tailored microbiome-directed therapeutics treatments. However, the complexity of microbial variations, due to interactions with the host, other microbes, and environmental factors, makes it challenging to identify how microbiota colonize in the human gut. Here, we describe a novel multiscale framework for COmputing the DYnamics of the gut microbiota (CODY), which enables the quantification of spatiotemporal-specific variations of gut microbiome abundance profiles, without a prior knowledge of microbiome interactions. Importantly, the predictive power of CODY is demonstrated using cross-sectional data from two longitudinal metagenomics studies—the microbiota development during early infancy and during short-term diet intervention of obese adults.