Abstract
BackgroundThe microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill. We hypothesized that differences in microbiota composition across vendors can influence murine models of pulmonary lipopolysaccharide (LPS) inflammation and Gram-negative pneumonia.MethodsA multi-vendor approach was used with genetically similar mice derived from three different vendors (Janvier, Envigo, Charles River). This model was employed to study the effect on the host response to a pulmonary LPS challenge (1 μg Klebsiella pneumoniae LPS, intranasal), as well as experimental K. pneumoniae infection (ATCC43816, 1 × 104 CFU, intranasal).ResultsGut microbiota analysis revealed profound intervendor differences in bacterial composition as shown by beta diversity and at various taxonomic levels. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 release in lung and bronchoalveolar lavage fluid (BALF) were determined 6 and 24 h after intranasal treatment with LPS. No differences were found between the groups, with the exception for Envigo, showing a higher level of TNFα in lung and BALF at 6 h compared to Janvier and Charles River. In another set of experiments, mice from different vendors were subjected to a clinically relevant model of Gram-negative pneumonia (K. pneumoniae). At 12 and 36 h post-infection, no intervendor differences were found in bacterial dissemination, or TNFα and IL-6 levels in the lungs. In line, markers for organ failure did not differ between groups.ConclusionsAlthough there was a marked variation in the gut microbiota composition of mice from different vendors, the hypothesized impact on our models of pulmonary inflammation and severe pneumonia was limited. This is of significance for experimental settings, showing that differences in gut microbiota do not have to lead to differences in outcome.
Highlights
The microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill with an impact on metabolism, the development of organ failure, and the host defense against pathogens [1,2,3,4,5]
Vendor affects bacterial gut microbiota composition Genetically similar inbred strains of wild-type mice maintained by three major vendors (Janvier, Envigo, and Charles River) showed profound differences in their gut bacterial communities
This study demonstrates that genetically similar C57BL/6J mice from different vendors can have significant differences in their gut microbiota
Summary
The microbiome has emerged as an important player in the pathophysiology of a whole spectrum of diseases that affect the critically ill with an impact on metabolism, the development of organ failure, and the host defense against pathogens [1,2,3,4,5]. The severity of illness was shown to be dependent on the vendor of the mice used for the fecal injections [7] This can be especially alarming considering the fact that replications of studies across the world are often done with mice from different vendors or facilities, which can show significant differences in the composition of their gut microbiota [11]. We hypothesized that differences in microbiota composition across vendors can influence murine models of pulmonary lipopolysaccharide (LPS) inflammation and Gram-negative pneumonia
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