Abstract

Dynamic changes in microbial communities play an important role in human health and disease. Specifically, deciphering how microbial species in a community interact with each other and their environment can elucidate mechanisms of disease, a problem typically investigated using tools from community ecology. Yet, such methods require measurements of absolute densities, whereas typical datasets only provide estimates of relative abundances. Here, we systematically investigate models of microbial dynamics in the simplex of relative abundances. We derive a new nonlinear dynamical system for microbial dynamics, termed "compositional" Lotka-Volterra (cLV), unifying approaches using generalized Lotka-Volterra (gLV) equations from community ecology and compositional data analysis. On three real datasets, we demonstrate that cLV recapitulates interactions between relative abundances implied by gLV. Moreover, we show that cLV is as accurate as gLV in forecasting microbial trajectories in terms of relative abundances. We further compare cLV to two other models of relative abundance dynamics motivated by common assumptions in the literature-a linear model in a log-ratio transformed space, and a linear model in the space of relative abundances-and provide evidence that cLV more accurately describes community trajectories over time. Finally, we investigate when information about direct effects can be recovered from relative data that naively provide information about only indirect effects. Our results suggest that strong effects may be recoverable from relative data, but more subtle effects are challenging to identify.

Highlights

  • The completion of the second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease [1]

  • Dynamic changes in microbial communities play an important role in human health and disease

  • We show that the parameters of compositional” Lotka-Volterra (cLV) recapitulate interactions in the simplex implied by generalized LotkaVolterra (gLV)

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Summary

Introduction

The completion of the second phase of the Human Microbiome Project has highlighted the relationship between dynamic changes in the microbiome and disease [1]. Temporal changes in the vaginal microbiome during pregnancy, for example, are associated with increased risk for preterm birth [2], and the intestinal microbiome of individuals with inflammatory bowel disease undergoes large-scale changes during active and inactive periods of the disease [3]. Changes to the intestinal microbiome are predictive of treatment outcomes. In hospitalized patients the intestinal microbiome provides resistance to pathogenic bacteria, and depletion of the community in response to antibiotics increases risk of infection [4, 5]. Some treatments for disease are mediated through the intestinal microbiome itself [6]. Recent research has focused on temporal modeling of the microbiome with the aim of understanding the etiology of disease, predicting patient outcomes for personalized medicine, and elucidation of microbe-microbe or host-microbiome interactions [5, 7, 8]. The gut microbiome is a complex ecosystem, making realization of these goals a challenging task

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