In this study we investigated how the concentrations, pairwise correlations, and ratios of 202 free circulating blood metabolites and lipids vary with age in a panel of n=1882 subjects ranging from 48 to 94 years. We report a statistically significant sex-dependent association with age of a panel of metabolites and lipids involving, in women cohort, linoleic acid, α-linoleic acid, and carnitine, and, in men sub-group, monoacylglycerols and lysophosphatidylcholines. Evaluating the association of correlations among metabolites and/or lipids with age, we found that phosphatidylcholines correlations tend to have a positive trend associated with age in women, and monoacylglycerols and lysophosphatidylcholines correlations tend to have a negative trend associated with age in men. The association of ratio between molecular features with age reveals that the ratio between decanoyl L-carnitine and lysophosphatidylcholine in women have a negative association with age, while the ratios between L-carnitine, L-acetylcarnitine, and phosphatidylcholines in men have a positive association with age. These results suggest an age-dependent remodeling of lipid metabolism that induces changes in cell membrane bilayer composition and cell cycle mechanisms. Furthermore, we conclude that lipidome is directly involved in this age-dependent differentiation. Our results demonstrate that, using a comprehensive approach to aging focused on the changes of concentrations and relationships thereof, as expressed by their correlations and ratios, it is possible to obtain relevant information about metabolic dynamics associated with age.
This study investigated the associations between the levels of 27 plasma metabolites, 114 lipoprotein parameters, determined using nuclear magnetic resonance spectroscopy, and the ABO blood groups and the Rhesus (Rh) blood system in a cohort of n = 840 Italian healthy blood donors of both sexes. We observed good multivariate discrimination between the metabolomic and lipoproteomic profiles of subjects with positive and negative Rh. In contrast, we did not observe significant discrimination for the ABO blood group pairwise comparisons, suggesting only slight metabolic differences between these group-specific metabolic profiles. We report univariate associations (P-value < 0.05) between the subfraction HDL1 related to Apo A1, the subfraction HDL2 related to cholesterol and phospholipids, and the particle number of LDL2 related to free cholesterol, cholesterol, phospholipids, and Apo B and the ABO blood groups; we observed association of the lipid main fraction LDL4 related to free cholesterol, triglycerides, and Apo B; creatine; the particle number of LDL5; the subfraction LDL5 related to Apo B; the particle number of LDL4; and the subfraction LDL4 related to Apo B with Rh blood factors. These results suggest blood group-dependent (re)shaping of lipoprotein metabolism in healthy subjects, which may provide relevant information to explain the differential susceptibility to certain diseases observed in different blood groups.
Although the cystic fibrosis (CF) lung microbiome has been characterized in several studies, little is still known about the functions harboured by those bacteria, and how they change with disease status and antibiotic treatment. The aim of this study was to investigate the taxonomic and functional temporal dynamics of airways microbiome in a cohort of CF patients. Multiple sputum samples were collected over 15 months from 22 patients with chronic P. aeruginosa infection, for a total of 79 samples. DNA extracted from samples was subjected to shotgun metagenomic sequencing allowing either strain-level taxonomic profiling and assessment of the functional metagenomic repertoire. High inter-patient taxonomic heterogeneity was found with short-term compositional changes during exacerbations and following antibiotic treatment. Each patient exhibited distinct sputum microbial communities at the taxonomic level, and strain-specific colonization of traditional CF pathogens, including P. aeruginosa, and emerging pathogens. Sputum microbiome was found to be extraordinarily resilient following antibiotic treatment, with rapid recovery of taxa and metagenome-associated gene functions. In particular, a large core set of genes, including antibiotic resistance genes, were shared across patients despite observed differences in clinical status or antibiotic treatment, and constantly detected in the lung microbiome of all subjects independently from known antibiotic exposure, suggesting an overall microbiome-associated functions stability despite taxonomic fluctuations of the communities.IMPORTANCEWhile the dynamics of CF sputum microbial composition were highly patient-specific, the overall sputum metagenome composition was stable, showing a high resilience along time and antibiotic exposure. The high degree of redundancy in the CF lung microbiome could testifies ecological aspects connected to the disease that were never considered so far, as the large core-set of genes shared between patients despite observed differences in clinical status or antibiotic treatment. Investigations on the actual functionality (e.g. by metatranscriptomics) of the identified core-set of genes could provide clues on genetic function of the microbiome to be targeted in future therapeutic treatments.
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