18 research outputs found
Non-targeted metabolomics and lipidomics LC-MS data from maternal plasma of 180 healthy pregnant women
BACKGROUND: Metabolomics has the potential to be a powerful and sensitive approach for investigating the low molecular weight metabolite profiles present in maternal fluids and their role in pregnancy. FINDINGS: In this Data Note, LC–MS metabolome, lipidome and carnitine profiling data were collected from 180 healthy pregnant women, representing six time points spanning all three trimesters, and providing sufficient coverage to model the progression of normal pregnancy. CONCLUSIONS: As a relatively large scale, real-world dataset with robust numbers of quality control samples, the data are expected to prove useful for algorithm optimization and development, with the potential to augment studies into abnormal pregnancy. All data and ISA-TAB format enriched metadata are available for download in the MetaboLights and GigaScience databases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13742-015-0054-9) contains supplementary material, which is available to authorized users
Microbiome-derived bile acids contribute to elevated antigenic response and bone erosion in rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic, disabling and incurable autoimmune
disease. It has been widely recognized that gut microbial dysbiosis is an
important contributor to the pathogenesis of RA, although distinct alterations
in microbiota have been associated with this disease. Yet, the metabolites that
mediate the impacts of the gut microbiome on RA are less well understood. Here,
with microbial profiling and non-targeted metabolomics, we revealed profound
yet diverse perturbation of the gut microbiome and metabolome in RA patients in
a discovery set. In the Bacteroides-dominated RA patients, differentiation of
gut microbiome resulted in distinct bile acid profiles compared to healthy
subjects. Predominated Bacteroides species expressing BSH and 7a-HSDH
increased, leading to elevated secondary bile acid production in this subgroup
of RA patients. Reduced serum fibroblast growth factor-19 and dysregulated bile
acids were evidence of impaired farnesoid X receptor-mediated signaling in the
patients. This gut microbiota-bile acid axis was correlated to ACPA. The
patients from the validation sets demonstrated that ACPA-positive patients have
more abundant bacteria expressing BSH and 7a-HSDH but less Clostridium scindens
expressing 7a-dehydroxylation enzymes, together with dysregulated microbial
bile acid metabolism and more severe bone erosion than ACPA-negative ones.
Mediation analyses revealed putative causal relationships between the gut
microbiome, bile acids, and ACPA-positive RA, supporting a potential causal
effect of Bacteroides species in increasing levels of ACPA and bone erosion
mediated via disturbing bile acid metabolism. These results provide insights
into the role of gut dysbiosis in RA in a manifestation-specific manner, as
well as the functions of bile acids in this gut-joint axis, which may be a
potential intervention target for precisely controlling RA conditions.Comment: 38 pages, 6 figure
Genome-Wide Transcriptome and Antioxidant Analyses on Gamma-Irradiated Phases of Deinococcus radiodurans R1
Adaptation of D. radiodurans cells to extreme irradiation environments requires dynamic interactions between gene expression and metabolic regulatory networks, but studies typically address only a single layer of regulation during the recovery period after irradiation. Dynamic transcriptome analysis of D. radiodurans cells using strand-specific RNA sequencing (ssRNA-seq), combined with LC-MS based metabolite analysis, allowed an estimate of the immediate expression pattern of genes and antioxidants in response to irradiation. Transcriptome dynamics were examined in cells by ssRNA-seq covering its predicted genes. Of the 144 non-coding RNAs that were annotated, 49 of these were transfer RNAs and 95 were putative novel antisense RNAs. Genes differentially expressed during irradiation and recovery included those involved in DNA repair, degradation of damaged proteins and tricarboxylic acid (TCA) cycle metabolism. The knockout mutant crtB (phytoene synthase gene) was unable to produce carotenoids, and exhibited a decreased survival rate after irradiation, suggesting a role for these pigments in radiation resistance. Network components identified in this study, including repair and metabolic genes and antioxidants, provided new insights into the complex mechanism of radiation resistance in D. radiodurans
LC–MS-Based Urinary Metabolite Signatures in Idiopathic Parkinson’s Disease
Increasing
evidence has shown that abnormal metabolic phenotypes
in body fluids reflect the pathogenesis and pathophysiology of Parkinson’s
disease (PD). These body fluids include urine; however, the relationship
between, specifically, urinary metabolic phenotypes and PD is not
fully understood. In this study, urinary metabolites from a total
of 401 clinical urine samples collected from 106 idiopathic PD patients
and 104 normal control subjects were profiled by using high-performance
liquid chromatography coupled to high-resolution mass spectrometry.
Our study revealed significant correlation between clinical phenotype
and urinary metabolite profile. Metabolic profiles of idiopathic PD
patients differed significantly and consistently from normal controls,
with related metabolic pathway variations observed in steroidogenesis,
fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism,
tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism.
In the fruit fly <i>Drosophila melanogaster</i>, the alteration
of the kynurenine pathway in tryptophan metabolism corresponded with
pathogenic changes in the alpha-synuclein overexpressed <i>Drosophila</i> model of PD. The results suggest that LC–MS-based urinary
metabolomic profiling can reveal the metabolite signatures and related
variations in metabolic pathways that characterize PD. Consistent
PD-related changes across species may provide the basis for understanding
metabolic regulation of PD at the molecular level
Pregnancy-Induced Metabolic Phenotype Variations in Maternal Plasma
Metabolic
variations occur during normal pregnancy to provide the growing fetus
with a supply of nutrients required for its development and to ensure
the health of the woman during gestation. Mass spectrometry-based
metabolomics was employed to study the metabolic phenotype variations
in the maternal plasma that are induced by pregnancy in each of its
three trimesters. Nontargeted metabolomics analysis showed that pregnancy
significantly altered the profile of metabolites in maternal plasma.
The levels of six metabolites were found to change significantly throughout
pregnancy, with related metabolic pathway variations observed in biopterin
metabolism, phospholipid metabolism, amino acid derivatives, and fatty
acid oxidation. In particular, there was a pronounced elevation of
dihydrobiopterin (BH<sub>2</sub>), a compound produced in the synthesis
of dopa, dopamine, norepinephrine, and epinephrine, in the second
trimester, whereas it was markedly decreased in the third trimester.
The turnover of BH<sub>2</sub> and tryptophan catabolites indicated
that the fluctuations of neurotransmitters throughout pregnancy might
reveal the metabolic adaption in the maternal body for the growth
of the fetus. Furthermore, 11 lipid classes and 41 carnitine species
were also determined and this showed variations in the presence of
long-chain acylcarnitines and lysophospholipids in later pregnancy,
suggesting changes of acylcarnitines and lysophospholipids to meet
the energy demands in pregnant women. To our knowledge, this work
is the first report of dynamic metabolic signatures and proposed related
metabolic pathways in the maternal plasma for normal pregnancies and
provided the basis for time-dependent metabolic trajectory against
which disease-related disorders may be contrasted
Principal component analysis of transcriptome profiling in <i>D. radiodurans</i> R1.
<p>A, the plot of the principal component 1 (PC1) versus principal component 2 (PC2) was presented. B, Loadings plot of PC1. C, Hierarchical clustering analyses of the selected genes that have a high correlation with PC1. D, Loadings plot of PC2. E, Hierarchical clustering analyses of the selected genes that have a high correlation with PC2.</p
Expression patterns of selected genes for DNA repair pathway system (* <i>padj</i><0.1).
<p>A, base excision repair. B, nucleotide excision repair. C, homologous recombination. D. mismatch repair.</p
Strand-Specific RNA-seq analysis of the genes from <i>D. radiodurans</i> R1.
<p>Strand-specific coverage plot is shown. (Orange indicates the chromosome 1; violet, chromosome 2; green, plasmid 1; red, plasmid 2).</p