Modeling the temporal dynamics of the gut microbial community in adults and infants

Given the highly dynamic and complex nature of the human gut microbial community, the ability to identify and predict time-dependent compositional patterns of microbes is crucial to our understanding of the structure and functions of this ecosystem. One factor that could affect such time-dependent patterns is microbial interactions, wherein community composition at a given time point affects the microbial composition at a later time point. However, the field has not yet settled on the degree of this effect. Specifically, it has been recently suggested that only a minority of taxa depend on the microbial composition in earlier times. To address the issue of identifying and predicting temporal microbial patterns we developed a new model, MTV-LMM (Microbial Temporal Variability Linear Mixed Model), a linear mixed model for the prediction of microbial community temporal dynamics. MTV-LMM can identify time-dependent microbes (i.e., microbes whose abundance can be predicted based on the previous microbial composition) in longitudinal studies, which can then be used to analyze the trajectory of the microbiome over time. We evaluated the performance of MTV-LMM on real and synthetic time series datasets, and found that MTV-LMM outperforms commonly used methods for microbiome time series modeling. Particularly, we demonstrate that the effect of the microbial composition in previous time points on the abundance of taxa at later time points is underestimated by a factor of at least 10 when applying previous approaches. Using MTV-LMM, we demonstrate that a considerable portion of the human gut microbiome, both in infants and adults, has a significant time-dependent component that can be predicted based on microbiome composition in earlier time points. This suggests that microbiome composition at a given time point is a major factor in defining future microbiome composition and that this phenomenon is considerably more common than previously reported for the human gut microbiome.Author summary: The ability to characterize and predict temporal trajectories of the microbial community in the human gut is crucial to our understanding of the structure and functions of this ecosystem. In this study we develop MTV-LMM, a method for modeling time-series microbial community data. Using MTV-LMM we find that in contrast to previous reports, a considerable portion of microbial taxa in both infants and adults display temporal structure that is predictable using the previous composition of the microbial community. In reaching this conclusion we have adopted a number of concepts common in statistical genetics for use with longitudinal microbiome studies. We introduce concepts such as time-explainability and the temporal kinship matrix, which we believe will be of use to other researchers studying microbial dynamics, through the framework of linear mixed models. In particular we find that the association matrix estimated by MTV-LMM reveals known phylogenetic relationships and that the temporal kinship matrix uncovers known temporal structure in infant microbiome and inter-individual differences in adult microbiome. Finally, we demonstrate that MTV-LMM significantly outperforms commonly used methods for temporal modeling of the microbiome, both in terms of its prediction accuracy as well as in its ability to identify time-dependent taxa.