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Dynamics of the microbiota in response to host infection

Author: Belzer, C. · Gerber, G.K. · Roeselers, G. · Delaney, M. · DuBois, A. · Liu, Q. · Belavusava, V. · Yeliseyev, V. · Houseman, A. · Onderdonk, A. · Cavanaugh, C. · Bry, L.
Type:article
Date:2014
Source:PLoS ONE, 7, 9
Identifier: 513446
doi: doi:10.1371/journal.pone.0095534
Article number: e95534
Keywords: Biology · DNA 16S · Animal experiment · Animal model · Bacterial clearance · Bacterium detection · Cecum · Citrobacter rodentium · Colitis · Commensal · Descending colon · Gene sequence · Genus · Ileum · Intestine flora · Lactobacillus johnsonii · Lactobacillus reuteri · Microbial community · Microbial diversity · Nonhuman · Phylogeny · Phylum · Taxonomy · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · ELSS - Earth, Life and Social Sciences

Abstract

Longitudinal studies of the microbiota are important for discovering changes in microbial communities that affect the host. The complexity of these ecosystems requires rigorous integrated experimental and computational methods to identify temporal signatures that promote physiologic or pathophysiologic responses in vivo. Employing a murine model of infectious colitis with the pathogen Citrobacter rodentium, we generated a 2-month time-series of 16S rDNA gene profiles, and quantitatively cultured commensals, from multiple intestinal sites in infected and uninfected mice. We developed a computational framework to discover time-varying signatures for individual taxa, and to automatically group signatures to identify microbial sub-communities within the larger gut ecosystem that demonstrate common behaviors. Application of this model to the 16S rDNA dataset revealed dynamic alterations in the microbiota at multiple levels of resolution, from effects on systems-level metrics to changes across anatomic sites for individual taxa and species. These analyses revealed unique, time-dependent microbial signatures associated with host responses at different stages of colitis. Signatures included a Mucispirillum OTU associated with early disruption of the colonic surface mucus layer, prior to the onset of symptomatic colitis, and members of the Clostridiales and Lactobacillales that increased with successful resolution of inflammation, after clearance of the pathogen. Quantitative culture data validated findings for predominant species, further refining and strengthening model predictions. These findings provide new insights into the complex behaviors found within host ecosystems, and define several time-dependent microbial signatures that may be leveraged in studies of other infectious or inflammatory conditions. © 2014 Belzer et al.