title: Inference of Network Dynamics and Metabolic Interactions in the Gut Microbiome.
abstract: We present a novel methodology to construct a Boolean dynamic model from time series metagenomic information and integrate this modeling with genome-scale metabolic network reconstructions to identify metabolic underpinnings for microbial interactions. We apply this in the context of a critical health issue: clindamycin antibiotic treatment and opportunistic Clostridium difficile infection. Our model recapitulates known dynamics of clindamycin antibiotic treatment and C. difficile infection and predicts therapeutic probiotic interventions to suppress C. difficile infection. Genome-scale metabolic network reconstructions reveal metabolic differences between community members and are used to explore the role of metabolism in the observed microbial interactions. In vitro experimental data validate a key result of our computational model, that B. intestinihominis can in fact slow C. difficile growth.
authors.affiliation: College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, United States of America; University of Virginia Cancer Center, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Steinway
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Biggs
authors.affiliation: University of Virginia Cancer Center, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Papin
authors.affiliation: Department of Physics, Pennsylvania State University, University Park, Pennsylvania, United States of America.
authors.forename: Reka
authors.initials: R
authors.lastname: Albert
mesh_terms: D000465:Algorithms; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use; D002981:Clindamycin / Q000737:chemistry; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000382:microbiology*; D018920:Coculture Techniques; D003198:Computer Simulation; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D053858:Metabolic Networks and Pathways; D051379:Mice; D064307:Microbiota
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin