Rationale Biological processes continuously fluctuate due to non-linear interactions with other biological processes and external perturbations. A previous analysis showed that in patients with asthma physiological and inflammatory processes are regulated differently compared to healthy individuals, which leads to a loss of adaptive capacity in response to e.g. a viral challenge (PMID: 31687927). In this study we aimed to determine fluctuation patterns of metabolic pathways in patient with asthma and healthy individuals by analysis of the urine metabolome, both in stable phase and after a viral challenge. Methods Urine samples of 11 patients with asthma and 12 healthy individuals were collected 3 times a week for a duration of 7 weeks. Samples were analysed by ultra-high-performance liquid chromatography combined with tandem mass spectrometry, both in the positive and negative ion mode. The average fluctuation per metabolite was calculated as the mean squared difference in abundance between two consecutive measurements adjusted for the time interval. The difference between asthma and healthy were normalized based on the average abundance and the metabolites with the greatest difference were further analysed using metaboanalyst.ca to determine the most dominant metabolic pathways. Results As a first approach we selected the metabolites from the positive ion analysis that showed the largest fluctuations in urine from both asthma patients and healthy individuals. After that we determined which pathways were implicated most, thus being discriminatory between asthma and health. Table 1 shows the most discriminative metabolites and its pathways (mean A-H difference in all metabolites is -0.36). The fluctuations of the lysine degradation were the highest in patients with asthma. In healthy subject the fluctuations of the glyoxylate and dicarboxylate metabolism and tryptophan metabolism, glycine, serine and threonine metabolism and purine metabolism (all KEGG pathways) were highest. We have previously studied the tryptophan metabolism in asthma and healthy subjects in conjunction with a rhinovirus challenge (PMID: 23882022), showing that in asthma there was an enhanced systemic tryptophan metabolism, but a reduced metabolism in the airways. In the current analysis we found a larger fluctuation pattern for tryptophan in healthy individuals compared to patients with asthma. Conclusion Our fluctuation analysis of urine metabolites from asthma patients and healthy individuals showed marked differences in the fluctuation of metabolic pathways involving a number of amino acids and purines. The smaller fluctuation in tryptophan metabolism in asthma is consistent with the reduced capacity in controlling inflammation in response to a viral challenge.
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