title: Mathematical modeling of primary succession of murine intestinal microbiota.
abstract: Understanding the nature of interpopulation interactions in host-associated microbial communities is critical to understanding gut colonization, responses to perturbations, and transitions between health and disease. Characterizing these interactions is complicated by the complexity of these communities and the observation that even if populations can be cultured, their in vitro and in vivo phenotypes differ significantly. Dynamic models are the cornerstone of computational systems biology and a key objective of computational systems biologists is the reconstruction of biological networks (i.e., network inference) from high-throughput data. When such computational models reflect biology, they provide an opportunity to generate testable hypotheses as well as to perform experiments that are impractical or not feasible in vivo or in vitro. We modeled time-series data for murine microbial communities using statistical approaches and systems of ordinary differential equations. To obtain the dense time-series data, we sequenced the 16S ribosomal RNA (rRNA) gene from DNA isolated from the fecal material of germfree mice colonized with cecal contents of conventionally raised animals. The modeling results suggested a lack of mutualistic interactions within the community. Among the members of the Bacteroidetes, there was evidence for closely related pairs of populations to exhibit parasitic interactions. Among the Firmicutes, the interactions were all competitive. These results suggest future animal and in silico experiments. Our modeling approach can be applied to other systems to provide a greater understanding of the dynamics of communities associated with health and disease.
authors.affiliation: Department of Microbiology and Immunology and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109.
authors.forename: Simeone
authors.initials: S
authors.lastname: Marino
authors.forename: Nielson T
authors.initials: NT
authors.lastname: Baxter
authors.forename: Gary B
authors.initials: GB
authors.lastname: Huffnagle
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Schloss
mesh_terms: D000465:Algorithms; D000818:Animals; D041963:Bacteroidetes; D019295:Computational Biology / Q000379:methods; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D020459:Genes, rRNA; D007422:Intestines / Q000382:microbiology*; D007778:Lactobacillus; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D008962:Models, Theoretical; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S
keywords: 454 sequencing; culture independent; dynamical systems; microbial ecology; microbiome