The intestinal microbiota impacts nutritional immunity and resistance to Acinetobacter baumannii pneumonia

This treatment has been associated with subsequent infections by the emerging nosocomial pathogen Acinetobacter baumannii; however, the mechanisms underlying this association remain unclear. Here, we demonstrate in a murine model that prophylactic broad-spectrum antibiotic administration drives susceptibility to intranasal infections with A. baumannii, and that reconstitution of the intestinal microbiota by fecal microbiota transplant restores control of infection, implicating microbiota dysbiosis as a key driver of pulmonary disease.

Using single-cell RNA sequencing, we determine that prophylaxis suppresses phagocyte effector functions in the lung, including nutritional immunity pathways that restrict pathogen access to essential nutrient metals. Depletion studies identify neutrophils and inflammatory monocytes as central mediators of microbiota-dependent protection, and infection of mice lacking nutritional immunity components lipocalin-2 or calprotectin abrogates the effects of prophylaxis, establishing a causal linkage between microbiota dysbiosis and impaired phagocyte-mediated nutritional immunity.