Three distinct pneumotypes characterize the microbiome of the lung in BALB/cJ mice.

Abstract

Abstract Bacteria can rarely be isolated from normal healthy lungs using conventional culture techniques, supporting the traditional belief that the lungs are sterile. Yet recent studies using next generation sequencing report that bacterial DNA commonly found in the upper respiratory tract (URT) is present at lower levels in the lungs. Interpretation of that finding is complicated by the technical limitations and potential for contamination introduced when dealing with low biomass samples. The current work sought to overcome those limitations to clarify the number, type and source of bacteria present in the lungs of normal mice. Results showed that the oral microbiome is large, less diverse and highly conserved whereas murine lung samples fall into three distinct patterns. Most pulmonary samples were sterile, as they lacked culturable bacteria and their bacterial DNA content did not differ from background. 11% of samples contained comparatively higher amounts of bacterial DNA whose composition mimicked that detected in the URT, consistent with (micro)aspiration. A final group (26%) contained smaller amounts of microbial DNA whose composition was similar to that of rodent chow, perhaps acquired by inspiration of food fragments. This work eliminated the bias introduced by aspiration-contaminated samples to establish that three distinct microbiome pneumotypes are present in normal murine lungs of BALB/cJ mice. The presented findings contribute to the knowledge in the growing field of microbiome research in the respiratory tract and are of relevance to researchers evaluating respiratory diseases in murine models.