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Integrative metabolomics as emerging tool to study autophagy regulation.

ABSTRACT: Recent technological developments in metabolomics research have enabled in-depth characterization of complex metabolite mixtures in a wide range of biological, biomedical, environmental, agricultural, and nutritional research fields. Nuclear magnetic resonance spectroscopy and mass spectrometry are the two main platforms for performing metabolomics studies. Given their broad applicability and the systemic insight into metabolism that can be obtained it is not surprising that metabolomics becomes increasingly popular in basic biological research. In this review, we provide an overview on key metabolites, recent studies, and future opportunities for metabolomics in studying autophagy regulation. Metabolites play a pivotal role in autophagy regulation and are therefore key targets for autophagy research. Given the recent success of metabolomics, it can be expected that metabolomics approaches will contribute significantly to deciphering the complex regulatory mechanisms involved in autophagy in the near future and promote understanding of autophagy and autophagy-related diseases in living cells and organisms.

SUBMITTER: Stryeck S

PROVIDER: S-EPMC5568430 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Integrative metabolomics as emerging tool to study autophagy regulation.

Stryeck Sarah S Birner-Gruenberger Ruth R Madl Tobias T

Microbial cell (Graz, Austria) 20170713 8

Recent technological developments in metabolomics research have enabled in-depth characterization of complex metabolite mixtures in a wide range of biological, biomedical, environmental, agricultural, and nutritional research fields. Nuclear magnetic resonance spectroscopy and mass spectrometry are the two main platforms for performing metabolomics studies. Given their broad applicability and the systemic insight into metabolism that can be obtained it is not surprising that metabolomics becomes ...[more]

PMID: 28845422

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Project description:BackgroundInfants with bronchiolitis are at high risk for developing childhood asthma. While genome-wide association studies suggest common genetic susceptibilities between these conditions, the mechanisms underlying the link remain unclear.ObjectiveThrough integrated genetics-metabolomics analysis in this high-risk population, we sought to identify genetically driven metabolites associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility.MethodsIn a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we profiled the nasopharyngeal metabolome and genotyped the whole genome at hospitalization. We identified asthma-related metabolites from 283 measured compounds and conducted metabolite quantitative trait loci (mtQTL) analyses. We further examined the mtQTL associations by testing shared genetic loci for metabolites and asthma using colocalization analysis and the concordance between the loci and known asthma-susceptibility genes.ResultsIn 744 infants hospitalized with bronchiolitis, 28 metabolites (e.g., docosapentaenoate [DPA], 1,2-dioleoyl-sn-glycero-3-phosphoglycerol, sphingomyelin) were associated with asthma risk. A total of 349 loci were associated with these metabolites-161 for non-Hispanic white, 120 for non-Hispanic black, and 68 for Hispanics. Of these, there was evidence for 30 shared loci between 16 metabolites and asthma risk (colocalization posterior probability ≥0.5). The significant SNPs within loci were aligned with known asthma-susceptibility genes (e.g., ADORA1, MUC16).ConclusionThe integrated genetics-metabolomics analysis identified genetically driven metabolites during infancy that are associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility. Identifying these metabolites and genetic loci should advance research into the functional mechanisms of the infant bronchiolitis-childhood asthma link.

Project description:ObjectiveGut microbiota and their metabolites play an important role in the development of type 2 diabetes mellitus (T2DM). This research was designed to study the relationship between gut microbiota and faecal metabolites of Uyghur newly onset T2DM and impaired glucose regulation (IGR) patients.Materials and methodsA total of 60 different glycemic Uyghur subjects were enrolled and divided into T2DM, IGR, and normal glucose tolerance (NGT) groups. Metagenomics and LC-MS-based untargeted faecal metabolomics were employed. Correlations between bacterial composition and faecal metabolomics were evaluated.ResultsWe discovered that the composition and diversity of gut microbiota in newly onset T2DM and IGR were different from those in NGT. The α-diversity was higher in NGT than in T2DM and IGR; β-diversity analysis revealed apparent differences in the bacterial community structures between patients with T2DM, IGR, and NGT. LC-MS faecal metabolomics analysis discovered different metabolomics features in the three groups. Alchornoic acid, PE (14 : 0/20 : 3), PI, L-tyrosine, LysoPC (15 : 0), protorifamycin I, pimelic acid, epothilone A, 7-dehydro-desmosterol, L-lysine, LysoPC (14 : 1), and teasterone are the most significant differential enriched metabolites. Most of the differential enriched metabolites were involved in metabolic processes, including carbohydrate metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, and biosynthesis of amino acids. Procrustes analysis and correlation analysis identified correlations between gut microbiota and faecal metabolites. Matricin was positively correlated with Bacteroides and negatively correlated with Actinobacteria; protorifamycin I was negatively correlated with Actinobacteria; epothilone A was negatively correlated with Actinobacteria and positively correlated with Firmicutes; PA was positively correlated with Bacteroides and negatively correlated with Firmicutes; and cristacarpin was positively correlated with Actinobacteria; however, this correlation relationship does not imply causality.ConclusionsThis study used joint metagenomics and metabolomics analyses to elucidate the relationship between gut microbiota and faecal metabolites in different glycemic groups, and the result suggested that metabolic disorders and gut microbiota dysbiosis occurred in Uyghur T2DM and IGR. The results provide a theoretical basis for studying the pathological mechanism for further research.

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Integrative metabolomics as emerging tool to study autophagy regulation.

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Integrative metabolomics as emerging tool to study autophagy regulation.

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