Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection

摘要: Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis even death. To better understand dynamics mucosal immunity during C. infection from initiation through expansion resolution, we built a computational model immune response bacterium. The was calibrated using data mouse infection. demonstrates crucial role T helper 17 (Th17) effector responses colonic lamina propria luminal commensal bacteria populations clearance pathology, whereas regulatory (Treg) cells recovery phase. In addition, production anti-microbial peptides by inflamed epithelial activated neutrophils inhibit re-growth beneficial bacterial species. Computational simulations suggest that removal neutrophil cell derived inhibitions, separately together, on regrowth promote minimize pathology. Simulation results predict decrease markers, such as neutrophilic influx Th17 propria, length accelerated altered inhibition. modeling provides novel insights therapeutic value repopulating microbiome inducing Thus, immunity-gut microbiota interactions has potential guide development targeted fecal transplantation therapies context precision medicine interventions.