Beyond steady state: temporal variation in microbial communities

Abstract

Microbial communities exist in ever-changing environments. For example, the human microbiome is exposed to nutrients on a periodic basis and is occasionally exposed to novel chemical compounds, such as pharmaceutical drugs. The impact of this temporal variability on microbial communities is not well understood, with existing conceptual and mathematical models often assuming the existence of a stable steady state. In my thesis work, I probed the impact of temporal variability on microbial communities in a variety of contexts. In my first chapter, I used theory to explore how noise in cell metabolism can influence microbial communities. Chemical variability is not only found in microbes’ environments, but also within the microbes themselves. I found that noisy metabolism can promote the sharing of metabolites between microbes, providing a potential explanation for why such sharing is so widely observed in nature. In my second and third chapters, I employed mathematical modeling to characterize the response of microbial communities to variable nutrient supply. My collaborator and I found that fluctuating nutrient supply could drastically alter community diversity, in extreme cases causing community collapse. These changes could be explained by a single ‘early-bird’ effect in which bacteria use early growth advantages to out-grow otherwise superior competitors. In my fourth chapter, I characterized the human microbiome’s response to novel chemical perturbations. Drug treatments often fail for unknown reasons, and one possible cause is off-target metabolism by the human microbiome. My collaborators and I developed an experimental method for assaying the capacity of human gut microbiomes to metabolize drugs, finding that a substantial fraction of drugs are metabolized and that this metabolism is highly variable between people.