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Environmental Health Perspectives Sep 2023Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive...
Urinary Paraben Concentrations and Associations with the Periconceptional Urinary Metabolome: Untargeted and Targeted Metabolomics Analyses of Participants from the Early Pregnancy Study.
BACKGROUND
Parabens, found in everyday items from personal care products to foods, are chemicals with endocrine-disrupting activity, which has been shown to influence reproductive function.
OBJECTIVES
This study investigated whether urinary concentrations of methylparaben, propylparaben, or butylparaben were associated with the urinary metabolome during the periconceptional period, a critical window for female reproductive function. Changes to the periconceptional urinary metabolome could provide insights into the mechanisms by which parabens could impact fertility.
METHODS
Urinary paraben concentrations were measured in paired pre- and postconception urine samples from 42 participants in the Early Pregnancy Study, a prospective cohort of 221 women attempting to conceive. We performed untargeted and targeted metabolomics analyses using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We used principal component analysis, orthogonal partial least-squares discriminant analysis, and permutation testing, coupled with univariate statistical analyses, to find metabolites associated with paraben concentration at the two time points. Potential confounders were identified with a directed acyclic graph and used to adjust results with multivariable linear regression. Metabolites were identified using fragmentation data.
RESULTS
Seven metabolites were associated with paraben concentration (variable importance to projection score , false discovery rate-corrected ). We identified four diet-related metabolites to the Metabolomics Standards Initiative (MSI) certainty of identification level 2, including metabolites from smoke flavoring, grapes, and olive oil. One metabolite was identified to the class level only (MSI level 3). Two metabolites were unidentified (MSI level 4). After adjustment, three metabolites remained associated with methylparaben and propylparaben, two of which were diet-related. No metabolomic markers of endocrine disruption were associated with paraben concentrations.
DISCUSSION
This study identified novel relationships between urinary paraben concentrations and diet-related metabolites but not with metabolites on endocrine-disrupting pathways, as hypothesized. It demonstrates the feasibility of integrating untargeted metabolomics data with environmental exposure information and epidemiological adjustment for confounders. The findings underscore a potentially important connection between diet and paraben exposure, with applications to nutritional epidemiology and dietary exposure assessment. https://doi.org/10.1289/EHP12125.
Topics: Pregnancy; Humans; Female; Parabens; Prospective Studies; Metabolomics; Metabolome
PubMed: 37702489
DOI: 10.1289/EHP12125 -
International Journal of Molecular... Sep 2022Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma... (Review)
Review
Soft tissue sarcomas (STS) prognosis is disappointing, with current treatment strategies being based on a "fit for all" principle and not taking distinct sarcoma subtypes specificities and genetic/metabolic differences into consideration. The paucity of precision therapies in STS reflects the shortage of studies that seek to decipher the sarcomagenesis mechanisms. There is an urge to improve STS diagnosis precision, refine STS classification criteria, and increase the capability of identifying STS prognostic biomarkers. Single-omics and multi-omics studies may play a key role on decodifying sarcomagenesis. Metabolomics provides a singular insight, either as a single-omics approach or as part of a multi-omics strategy, into the metabolic adaptations that support sarcomagenesis. Although STS metabolome is scarcely characterized, untargeted and targeted metabolomics approaches employing different data acquisition methods such as mass spectrometry (MS), MS imaging, and nuclear magnetic resonance (NMR) spectroscopy provided important information, warranting further studies. New chromatographic, MS, NMR-based, and flow cytometry-based methods will offer opportunities to therapeutically target metabolic pathways and to monitorize the response to such metabolic targeting therapies. Here we provide a comprehensive review of STS omics applications, comprising a detailed analysis of studies focused on the metabolic landscape of these tumors.
Topics: Biomarkers; Humans; Metabolome; Metabolomics; Sarcoma; Soft Tissue Neoplasms
PubMed: 36232732
DOI: 10.3390/ijms231911430 -
Nature Communications Jan 2023Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what...
Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.
Topics: Animals; Male; Caenorhabditis elegans; Metabolome; Caenorhabditis elegans Proteins; Metabolomics; Longevity
PubMed: 36658169
DOI: 10.1038/s41467-023-36040-y -
Current Opinion in Plant Biology Jun 2023Whilst the study of metabolites can arguably be traced back several hundred years it began in earnest in the 20 century with studies based on single metabolites or... (Review)
Review
Whilst the study of metabolites can arguably be traced back several hundred years it began in earnest in the 20 century with studies based on single metabolites or simple metabolic pathways. The advent of metabolomics and in particular the adoption of high-resolution mass spectrometry now means we can faithfully annotate and quantify in excess of 1000 plant metabolites. Whilst this is an impressive leap it falls well short of the estimated number of metabolites in the plant kingdom. This, whilst considerable and important insights have been achieved using commonly utilized approaches, there is a need to improve the coverage of the metabolome. Here, we review three largely complementary strategies (i) methods based on using chemical libraries (ii) methods based on molecular networking and (iii) approaches that link metabolomics and genetic variance. It is our contention that using all three approaches in tandem represents the best approach to tackle this challenge.
Topics: Metabolome; Metabolomics; Plants
PubMed: 36689903
DOI: 10.1016/j.pbi.2022.102335 -
Investigative Ophthalmology & Visual... May 2021Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and...
PURPOSE
Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and blindness. The aim of this review is to provide current metabolic profiles for glaucoma through a summary and analysis of reported metabolites associated with glaucoma.
METHODS
We searched PubMed and Web of Science for metabolomics studies of humans on glaucoma published before November 11, 2020. Studies were included if they assessed the biomarkers of any types of glaucoma and performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach. Pathway enrichment analysis and topology analysis were performed to generate a global view of metabolic signatures related to glaucoma using the MetaboAnalyst 3.0.
RESULTS
In total, 18 articles were included in this review, among which 13 studies were focused on open-angle glaucoma (OAG). Seventeen metabolites related to OAG were repeatedly identified, including seven amino acids (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholine (PC aa C34:2, PC aa C36:4), three complements (acetylcarnitine, propionylcarnitine, butyrylcarnitine), carnitine, glutamine, hypoxanthine, spermine, and spermidine. The pathway analysis implied a major role of amino metabolism in OAG pathophysiology and revealed the metabolic characteristics between different biological samples.
CONCLUSIONS
In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma. Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.
Topics: Biomarkers; Glaucoma, Open-Angle; Humans; Metabolome; Metabolomics
PubMed: 33956051
DOI: 10.1167/iovs.62.6.9 -
Current Opinion in Chemical Biology Oct 2013Metabolomics provides a direct functional read-out of the physiological status of an organism and is in principle ideally suited to describe someone's health status.... (Review)
Review
Metabolomics provides a direct functional read-out of the physiological status of an organism and is in principle ideally suited to describe someone's health status. Whereas only a limited number of small metabolites are used in the clinics, in inborn errors of metabolism an extensive repertoire of metabolites are used as biomarkers. We discuss that the proper clinical phenotyping is crucial to find biomarkers and obtain biological insights for multifactorial diseases. This requires to study the phenotype dynamics including the concepts of homeostasis and allostasis, that is, the ability to adapt and cope with a challenge. We also elaborate that biology-driven metabolomics platforms (i.e. development of metabolomics technology driven by the need of studying and answering important biomedical questions) addressing clinically relevant pathways and at the same time providing absolute concentrations are key to allow discovery and validation of biomarkers across studies and labs. Following individuals over years will require high throughput metabolomics approaches, which are emerging for nuclear magnetic resonance spectroscopy and direct-infusion mass spectrometry, but should also include the biochemical networks needed for personalized health monitoring.
Topics: Animals; Biomarkers; Humans; Metabolome; Metabolomics; Phenotype
PubMed: 23849548
DOI: 10.1016/j.cbpa.2013.06.015 -
Molecules (Basel, Switzerland) May 2023Ion mobility-mass spectrometry (IM-MS) is a powerful separation technique providing an additional dimension of separation to support the enhanced separation and... (Review)
Review
Ion mobility-mass spectrometry (IM-MS) is a powerful separation technique providing an additional dimension of separation to support the enhanced separation and characterization of complex components from the tissue metabolome and medicinal herbs. The integration of machine learning (ML) with IM-MS can overcome the barrier to the lack of reference standards, promoting the creation of a large number of proprietary collision cross section (CCS) databases, which help to achieve the rapid, comprehensive, and accurate characterization of the contained chemical components. In this review, advances in CCS prediction using ML in the past 2 decades are summarized. The advantages of ion mobility-mass spectrometers and the commercially available ion mobility technologies with different principles (e.g., time dispersive, confinement and selective release, and space dispersive) are introduced and compared. The general procedures involved in CCS prediction based on ML (acquisition and optimization of the independent and dependent variables, model construction and evaluation, etc.) are highlighted. In addition, quantum chemistry, molecular dynamics, and CCS theoretical calculations are also described. Finally, the applications of CCS prediction in metabolomics, natural products, foods, and the other research fields are reflected.
Topics: Metabolomics; Metabolome; Mass Spectrometry; Databases, Factual; Machine Learning
PubMed: 37241791
DOI: 10.3390/molecules28104050 -
Plant & Cell Physiology Mar 2022The advancement of metabolomics in terms of techniques for measuring small molecules has enabled the rapid detection and quantification of numerous cellular metabolites....
The advancement of metabolomics in terms of techniques for measuring small molecules has enabled the rapid detection and quantification of numerous cellular metabolites. Metabolomic data provide new opportunities to gain a deeper understanding of plant metabolism that can improve the health of both plants and humans that consume them. Although major public repositories for general metabolomic data have been established, the community still has shortcomings related to data sharing, especially in terms of data reanalysis, reusability and reproducibility. To address these issues, we developed the RIKEN Plant Metabolome MetaDatabase (RIKEN PMM, http://metabobank.riken.jp/pmm/db/plantMetabolomics), which stores mass spectrometry-based (e.g. gas chromatography-MS-based) metabolite profiling data of plants together with their detailed, structured experimental metadata, including sampling and experimental procedures. Our metadata are described as Linked Open Data based on the Resource Description Framework using standardized and controlled vocabularies, such as the Metabolomics Standards Initiative Ontology, which are to be integrated with various life and biomedical science data using the World Wide Web. RIKEN PMM implements intuitive and interactive operations for plant metabolome data, including raw data (netCDF format), mass spectra (NIST MSP format) and metabolite annotations. The feature is suitable not only for biologists who are interested in metabolomic phenotypes, but also for researchers who would like to investigate life science in general through plant metabolomic approaches.
Topics: Databases, Factual; Gas Chromatography-Mass Spectrometry; Metabolome; Metabolomics; Plants; Reproducibility of Results
PubMed: 34918130
DOI: 10.1093/pcp/pcab173 -
Analytica Chimica Acta Oct 2009Metabolomics is an emerging area of research focused on measuring small molecules in biological samples. There are a number of different types of metabolomics, ranging... (Review)
Review
Metabolomics is an emerging area of research focused on measuring small molecules in biological samples. There are a number of different types of metabolomics, ranging from global profiling of all metabolites in a single sample to measurement of a selected group of analytes. Microfluidics and related technologies have been used in this research area with good success. The aim of this review article is to summarize the use of microfluidics in metabolomics. Direct application of microfluidics to the determination of small molecules is covered first. Next, important sample preparation methods developed for microfluidics and applicable to metabolomics are covered. Finally, a summary of metabolomic work as it relates to analysis of cellular events using microfluidics is covered.
Topics: Electrophoresis, Capillary; Immunoassay; Luminescent Measurements; Metabolome; Metabolomics; Microchip Analytical Procedures; Microfluidics; Spectrophotometry, Ultraviolet; Toxicity Tests
PubMed: 19800473
DOI: 10.1016/j.aca.2009.08.037 -
Life Science Alliance Aug 2023Microbial symbionts frequently localize within specific body structures or cell types of their multicellular hosts. This spatiotemporal niche is critical to host health,...
Microbial symbionts frequently localize within specific body structures or cell types of their multicellular hosts. This spatiotemporal niche is critical to host health, nutrient exchange, and fitness. Measuring host-microbe metabolite exchange has conventionally relied on tissue homogenates, eliminating dimensionality and dampening analytical sensitivity. We have developed a mass spectrometry imaging workflow for a soft- and hard-bodied cnidarian animal capable of revealing the host and symbiont metabolome in situ, without the need for a priori isotopic labelling or skeleton decalcification. The mass spectrometry imaging method provides critical functional insights that cannot be gleaned from bulk tissue analyses or other presently available spatial methods. We show that cnidarian hosts may regulate microalgal symbiont acquisition and rejection through specific ceramides distributed throughout the tissue lining the gastrovascular cavity. The distribution pattern of betaine lipids showed that once resident, symbionts primarily reside in light-exposed tentacles to generate photosynthate. Spatial patterns of these metabolites also revealed that symbiont identity can drive host metabolism.
Topics: Animals; Metabolomics; Metabolome; Symbiosis; Mass Spectrometry; Invertebrates
PubMed: 37202120
DOI: 10.26508/lsa.202301900