Metabolomic similarities between bronchoalveolar lavage fluid and plasma in humans and mice

Abstract

This observational study catalogues the overlap in metabolites between matched bronchoalveolar lavage fluid (BALF) and plasma, identifies the degree of congruence between these metabolomes in human and mouse, and determines how molecules may change in response to cigarette smoke (CS) exposure. Matched BALF and plasma was collected from mice (ambient air or CS-exposed) and humans (current or former smokers), and analyzed using mass spectrometry. There were 1155 compounds in common in all 4 sample types; fatty acyls and glycerophospholipids strongly overlapped between groups. In humans and mice, more than half of the metabolites present in BALF were also present in plasma. Mouse BALF and human BALF had a strong positive correlation with 2040 metabolites in common, suggesting that mouse models can be used to interrogate human lung metabolome changes. While power was affected by small sample size in the mouse study, the BALF metabolome appeared to be more affected by CS than plasma. CS-exposed mice showed increased plasma and BALF glycerolipids and glycerophospholipids. This is the first report cataloguing the metabolites present across mouse and human, BALF and plasma. Findings are relevant to translational studies where mouse models are used to examine human disease, and where plasma may be interrogated in lieu of BALF or lung tissue.

A prototypic small molecule database for bronchoalveolar lavage-based metabolomics

“…This appears to be related to the smoking status of the subjects, with subjects who were current smokers having a higher number of compounds present in their BALF compared to non-smokers or former smokers. This is consistent with our previous findings 21 .…”

“…A table of sample identifiers are described in ‘s_Study id.txt’ (Data Citation 1). BALF used in the external validation test study was collected from subjects ( n =5) from the COPDGene cohort as previously described and n =10 mice as previously described 21 . All samples were frozen at -80 °C prior to sample preparation and analysis.…”

“…For the BALF-DB external test study using mouse and COPDgene BALF samples, preparation has been previously described 21 . Blank samples were prepared using water as previously described 21 .…”

Amino Acid Biosynthetic Pathways Are Required for Klebsiella pneumoniae Growth in Immunocompromised Lungs and Are Druggable Targets during Infection

“…In addition, some of these pathways share molecular precursors with iron-acquiring siderophores critical for K. pneumoniae virulence (1,25). Importantly, BAL fluid in humans is similar in amino acid content to mice (39), suggesting that amino acids are too scarce in human lungs for K. pneumoniae to scavenge, and therefore targeting amino acid biosynthesis pathways could translate to the clinic. In addition, none of the clinical isolates were auxotrophic, indicating that amino acid biosynthetic pathways are intact and therefore potentially targetable in infectious strains.…”

Metabolomics in chronic lung diseases

“…Towards the discovery of biomarkers and in the pursuit of improved disease characterization, metabolomics has been employed in lung diseases to study a large number of sample types including urine, plasma and serum, cerebrospinal fluid, exhaled breath condensate (EBC), bronchoalveolar lavage fluid (BALF), saliva, intact tissue as well as cells and their extracts. Urine and blood are the most commonly used biofluids for metabolomic studies as both samples contain thousands of detectable metabolic features and can be collected using minimally invasive methods.…”