Differential metabolic host response to pathogens associated with community-acquired pneumonia

Abstract

Background: Metabolic changes induced by the host immune response to pathogens found in patients with community-acquired pneumonia (CAP) may provide insight into its pathogenesis. In this study, we characterized differences in the host metabolic response to common CAP-associated pathogens.

Method: Targeted metabolomic profiling was performed on serum samples obtained from hospitalized CAP patients (n = 119) at admission. We quantified 347 unique metabolites across multiple biochemical classes, including amines, acylcarnitines, and signaling lipids. We evaluated if unique associations between metabolite levels and specific CAP-associated pathogens could be identified.

Results: Several acylcarnitines were found to be elevated in C. burnetii and herpes simplex virus and lowered in M. pneumoniae as compared to other pathogens. Phenylalanine and kynurenine were found elevated in L. pneumophila as compared to other pathogens. S-methylcysteine was elevated in patients with M. pneumoniae, and these patients also showed lowered cortisol levels in comparison to almost all other pathogens. For the herpes simplex virus, we observed a unique elevation of eicosanoids and several amines. Many lysophosphatidylcholines showed an altered profile in C. burnetii versus S. pneumoniae, L. pneumophila, and respiratory syncytial virus. Finally, phosphatidylcholines were negatively affected by the influenza virus in comparison to S. pneumoniae.

Conclusions: In this exploratory analysis, metabolites from different biochemical classes were found to be altered in serum samples from patients with different CAP-associated pathogens, which may be used for hypothesis generation in studies on differences in pathogen host response and pathogenesis of CAP.

Keywords: Amines; Biomarkers; Carnitines; Community-acquired pneumonia; Immune response; Lipids; Metabolomics.

Fig. 1

Fold changes of carnitine and acylcarnitines as median values per pathogen group compared to CAP patients with other pathogens. Significant differences (q < 0.1 and FC > 20%) are marked with a green star. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Fold changes of organic acids, amino acids, and derivatives as median values per pathogen group compared to CAP patients with other pathogens. Significant differences (q < 0.1 and FC > 20%) are marked with a green star. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Fold changes of oxylipin, endocannabinoid, and cortisol as median values per pathogen group compared to CAP patients with other pathogens. Significant differences (q < 0.1 and FC > 20%) are marked with a green star. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Fold changes of phospholipids including (lyso)phosphatidylcholines median values per pathogen group as median values per pathogen group compared to CAP patients with other pathogens. Significant differences (q < 0.1 and FC > 20%) are marked with a green star. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 5

Overview of differential metabolic host response associations for community-acquired pneumonia-associated pathogens inferred from the current analysis. A pathogen symbol indicates that this patient group had the highest levels of metabolite(s) in the red box. Metabolites that were either not detected or detected without significant results are in white boxes. Enzymes are in ellipses, full lines are part of a metabolic pathway or transformation, and broken lines indicate an inducing or inhibiting effect. Abbreviations: see the abbreviation list. This figure was created with BioRender.com. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)