Vendor effects on murine gut microbiota and its influence on lipopolysaccharide-induced lung inflammation and Gram-negative pneumonia

Background The 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...

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Published in:Intensive care medicine experimental Vol. 8; no. 1; pp. 47 - 13
Main Authors: Wolff, Nora S., Jacobs, Max C., Haak, Bastiaan W., Roelofs, Joris J. T. H., de Vos, Alex F., Hugenholtz, Floor, Wiersinga, W. Joost
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 25.08.2020
Springer Nature B.V
SpringerOpen
Subjects:
Critical Care Medicine
Gram-negative bacteria
Gut microbiota
Infection
Inflammation
Intensive
Intensive care
Intestinal microbiota
Klebsiella pneumoniae
Lipopolysaccharide
Medicine
Medicine & Public Health
Microbiota
Pneumonia
Pulmonary Inflammation
Rodents
Sepsis
Tumor necrosis factor-TNF
Vendor
Infection
Pneumonia
Pulmonary Inflammation
Intestinal microbiota
Lipopolysaccharide
Sepsis
Vendor
ISSN:2197-425X, 2197-425X
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Summary:Background The 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. Methods A 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 × 10 4 CFU, intranasal). Results Gut 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. Conclusions Although 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.
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ISSN:2197-425X
2197-425X
DOI:10.1186/s40635-020-00336-w