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 an unprecedented 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 define a novel platform for combining orthogonal, untargeted approaches to shed new light on the gastrointestinal ecosystem.