title: Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases.
abstract: Improved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem.
authors.affiliation: Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Lichtman
authors.affiliation: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Ferreyra
authors.affiliation: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Ng
authors.affiliation: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Smits
authors.affiliation: Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Sonnenburg
authors.affiliation: Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94025, USA. Electronic address: josh.elias@stanford.edu.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Elias
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004194:Disease; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D005260:Female; D054884:Host-Pathogen Interactions; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D064307:Microbiota; D020543:Proteome
chemical_list: D000900:Anti-Bacterial Agents; D020543:Proteome
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