Dataset Information

Use of gas chromatography mass spectrometry to elucidate metabolites predicting the phenotypes of IgA nephropathy in hyper IgA mice.

ABSTRACT: IgA nephropathy, a common chronic kidney disease, has various possible outcomes. Therefore, the identification of novel prognostic biomarkers is needed. To this purpose, we used gas chromatography mass spectrometry to search for metabolites capable of predicting the phenotypes of IgA nephropathy in hyper IgA (HIGA) mice, an established model mice for IgA nephropathy. We measured the plasma metabolite levels in 12- and 22-week-old mice, prior to the manifestation of IgA nephropathy phenotypes, and statistically investigated the associations between these metabolites and the phenotypes of IgA nephropathy, such as the urine protein levels and histological phenotypes of the kidney at 32 weeks. We observed that in plasma samples collected from 12- and 22-week-old HIGA mice, the urinary protein levels were significantly associated with 8 and 10 metabolites, the glomerular cellular component levels were significantly associated with 8 and 7 metabolites, and the mesangial substrate levels were significantly associated with 8 and 8 metabolites, respectively. Among the candidate metabolites associated with the phenotypes of IgA nephropathy, coniferyl alcohol levels were significantly higher in HIGA mice at all of the 12, 22, and 32 weeks of age. Since this study was an observational study, we could not elucidate the underlying mechanisms; however, we were able to identify new candidate metabolites, such as coniferyl alcohol, as being potentially involved in the pathogenesis of IgA nephropathy. These results might help to develop novel laboratory tests and therapeutic reagents for IgA nephropathy in the future.

SUBMITTER: Kurano M

PROVIDER: S-EPMC6619804 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Use of gas chromatography mass spectrometry to elucidate metabolites predicting the phenotypes of IgA nephropathy in hyper IgA mice.

Kurano Makoto M Yatomi Yutaka Y

PloS one 20190710 7

IgA nephropathy, a common chronic kidney disease, has various possible outcomes. Therefore, the identification of novel prognostic biomarkers is needed. To this purpose, we used gas chromatography mass spectrometry to search for metabolites capable of predicting the phenotypes of IgA nephropathy in hyper IgA (HIGA) mice, an established model mice for IgA nephropathy. We measured the plasma metabolite levels in 12- and 22-week-old mice, prior to the manifestation of IgA nephropathy phenotypes, an ...[more]

PMID: 31291349

Similar Datasets

Project description:It has become increasingly important to qualitatively and quantitatively assess the volatile metabolites in a range of bodily fluids for use in monitoring health. There has been relatively little work on the quantitative analysis of compounds, particularly with respect to the effects of ethnicity or geographic location. A novel method for the quantification of compounds in stool using 13C labelled compounds as internal standards is presented. Using thermal desorption gas chromatography mass spectrometry, stool samples from 38 healthy volunteers were analysed. The 13C labelled compounds, acetone, ethyl butanoate, ethanoic acid, butanoic acid, 3-methylbutanoic acid, and indole, were added as internal standards. This process mimics the solubility characteristics of the compounds and thus the method was able to quantify the compounds within the solid stool. In total, 15 compounds were quantified: Dimethyl sulphide (26⁻25,626 ng/g), acetone (442⁻3006 ng/g), ethyl butanoate (39⁻2468 ng/g), ethyl 2-methylbutanoate (0.3⁻180 ng/g), dimethyl disulphide (35⁻1303 ng/g), 1-octen-3-one (12 ng/g), dimethyl trisulphide (10⁻410 ng/g), 1-octen-3-ol (0.4⁻58 ng/g), ethanoic acid (672⁻12,963 ng/g), butanoic acid (2493⁻11,553 ng/g), 3-methylbutanoic acid (64⁻8262 ng/g), pentanoic acid (88⁻21,886 ng/g), indole (290⁻5477 ng/g), and 3-methyl indole (37⁻3483 ng/g). Moreover, by altering the pH of the stool to pH 13 in conjunction with the addition of 13C trimethylamine, the method was successful in detecting and quantifying trimethylamine for the first time in stool samples (range 40⁻5312 ng/g). Statistical analysis revealed that samples from U.K. origin had five significantly different compounds (ethyl butanoate, 1-octen-3-ol, ethanoic acid, butanoic acid, pentanoic acid, and indole) from those of South American origin. However, there were no significant differences between vegetarian and omnivore samples. These findings are supported by pre-existing literature evidence. Moreover, we have tentatively identified 12 compounds previously not reported as having been found in stool.

Project description:Microbial communities exchange molecules with their environment, which plays a major role in regulating global biogeochemical cycles and climate. While extracellular metabolites are commonly measured in terrestrial and limnic ecosystems, the presence of salt in marine habitats limits the nontargeted analyses of the ocean exometabolome using mass spectrometry (MS). Current methods require salt removal prior to sample measurements, which can alter the molecular composition of the metabolome and limit the types of compounds detected by MS. To overcome these limitations, we developed a gas chromatography MS (GC-MS) method that avoids sample altering during salt removal and that detects metabolites down to nanomolar concentrations from less than 1 ml of seawater. We applied our method (SeaMet) to explore marine metabolomes in vitro and in vivo First, we measured the production and consumption of metabolites during the culture of a heterotrophic bacterium, Marinobacter adhaerens Our approach revealed successional uptake of amino acids, while sugars were not consumed. These results show that exocellular metabolomics provides insights into nutrient uptake and energy conservation in marine microorganisms. We also applied SeaMet to explore the in situ metabolome of coral reef and mangrove sediment porewaters. Despite the fact that these ecosystems occur in nutrient-poor waters, we uncovered high concentrations of sugars and fatty acids, compounds predicted to play a key role for the abundant and diverse microbial communities in coral reef and mangrove sediments. Our data demonstrate that SeaMet advances marine metabolomics by enabling a nontargeted and quantitative analysis of marine metabolites, thus providing new insights into nutrient cycles in the oceans.IMPORTANCE Nontargeted approaches using metabolomics to analyze metabolites that occur in the oceans is less developed than those for terrestrial and limnic ecosystems. One of the challenges in marine metabolomics is that salt limits metabolite analysis in seawater to methods requiring salt removal. Building on previous sample preparation methods for metabolomics, we developed SeaMet, which overcomes the limitations of salt on metabolite detection. Considering that the oceans contain the largest dissolved organic matter pool on Earth, describing the marine metabolome using nontargeted approaches is critical for understanding the drivers behind element cycles, biotic interactions, ecosystem function, and atmospheric CO2 storage. Our method complements both targeted marine metabolomic investigations as well as other "omics" (e.g., genomics, transcriptomics, and proteomics) approaches by providing an avenue for studying the chemical interaction between marine microbes and their habitats.

Dataset Information

Use of gas chromatography mass spectrometry to elucidate metabolites predicting the phenotypes of IgA nephropathy in hyper IgA mice.

Publications

Use of gas chromatography mass spectrometry to elucidate metabolites predicting the phenotypes of IgA nephropathy in hyper IgA mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure