First-passage-time statistics of growing microbial populations carry an imprint of initial conditions.

In exponential population growth, variability in the timing of individual division events and environmental factors (including stochastic inoculation) compound to produce variable growth trajectories. In several stochastic models of exponential growth we show power-law relationships that relate variability in the time required to reach a threshold population size to growth rate and inoculum size. Population-growth experiments in E.

A symbiotic physical niche in Drosophila melanogaster regulates stable association of a multi-species gut microbiota.

The gut is continuously invaded by diverse bacteria from the diet and the environment, yet microbiome composition is relatively stable over time for host species ranging from mammals to insects, suggesting host-specific factors may selectively maintain key species of bacteria. To investigate host specificity, we used gnotobiotic Drosophila, microbial pulse-chase protocols, and microscopy to investigate the stability of different strains of bacteria in the fly gut. We show that a host-constructed physical niche in the foregut selectively binds bacteria with strain-level specificity, stabilizing their colonization.

Stochastic microbiome assembly depends on context.

Observational studies reveal substantial variability in microbiome composition across individuals. Targeted studies in gnotobiotic animals underscore this variability by showing that some bacterial strains colonize deterministically, while others colonize stochastically. While some of this variability can be explained by external factors like environmental, dietary, and genetic differences between individuals, in this paper we show that for the model organism , interactions between bacteria can affect the microbiome assembly process, contributing to a baseline level of microbiome variability even among isogenic organisms that are identically reared, housed, and fed.

Control of ecological outcomes through deliberate parameter changes in a model of the gut microbiome.

The generalized Lotka-Volterra (gLV) equations are a mathematical proxy for ecological dynamics. We focus on a gLV model of the gut microbiome, in which the evolution of the gut microbial state is determined in part by pairwise interspecies interaction parameters that encode environmentally mediated resource competition between microbes. We develop an in silico method that controls the steady-state outcome of the system by adjusting these interaction parameters.

Steady-state reduction of generalized Lotka-Volterra systems in the microbiome.

The generalized Lotka-Volterra (gLV) equations, a classic model from theoretical ecology, describe the population dynamics of a set of interacting species. As the number of species in these systems grow in number, their dynamics become increasingly complex and intractable. We introduce steady-state reduction (SSR), a method that reduces a gLV system of many ecological species into two-dimensional subsystems that each obey gLV dynamics and whose basis vectors are steady states of the high-dimensional model.

Microbiome interactions shape host fitness.

Gut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host, in turn, shapes the gut microbiome. However, it is unclear to what extent individual species versus community interactions within the microbiome are linked to host fitness. Here, we combinatorially dissect the natural microbiome of and reveal that interactions between bacteria shape host fitness through life history tradeoffs.

In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations.

In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques.

Pre-Guideline Trends Associated with Chest Radiograph Usage for Pediatric Community-Acquired Pneumonia in Emergency Department Settings.

Background: Health care spending in the U.S. totaled $3 trillion in 2014 and continues to increase rapidly.