Abstract
The intestinal microbiota is a microbial ecosystem of crucial importance to human health. Understanding how the microbiota confers resistance against enteric pathogens and how antibiotics disrupt that resistance is key to the prevention and cure of intestinal infections. We present a novel method to infer microbial community ecology directly from time-resolved metagenomics. This method extends generalized Lotka–Volterra dynamics to account for external perturbations. Data from recent experiments on antibiotic-mediated Clostridium difficile infection is analyzed to quantify microbial interactions, commensal-pathogen interactions, and the effect of the antibiotic on the community. Stability analysis reveals that the microbiota is intrinsically stable, explaining how antibiotic perturbations and C. difficile inoculation can produce catastrophic shifts that persist even after removal of the perturbations. Importantly, the analysis suggests a subnetwork of bacterial groups implicated in protection against C. difficile. Due to its generality, our method can be applied to any high-resolution ecological time-series data to infer community structure and response to external stimuli.
Highlights
The intestinal microbiota has been receiving much attention lately
Recent advances in DNA sequencing and metagenomics are opening a window into the human microbiome revealing novel associations between certain microbial consortia and disease
We develop a method to analyze temporal community data accounting for timedependent external perturbations
Summary
The intestinal microbiota has been receiving much attention lately. Recent studies, propelled by metagenomics and nextgeneration DNA sequencing technologies, establish novel connections between the intestinal microbial species composition and diseases [1,2,3]. The recent developments in metagenomic high-throughput sequencing allow this by enabling the investigation of species composition directly without the need for culturing [13]. This has opened a new window into the microbial ecosystem residing in the intestinal tract. Our present view is that the intestinal microbiota is a relatively resilient ecosystem [14], with a composition that is quite stable over time [15,16] External perturbations, such as dramatic changes in diet [17] or antibiotic administration [18], can shift the composition. The reintroduction of anaerobic flora with high levels of Barnesiella sp. can clear intestines from highly abundant vancomycin-resistant Enteroccocus in mice [25]
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