Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 51 min 21 sec ago

metabolomics; +21 new citations

Wed, 15/08/2018 - 12:07
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +19 new citations

Tue, 14/08/2018 - 14:47
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/14PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Non-targeted metabolomics reveals alterations in liver and plasma of gilt-head bream exposed to oxybenzone.

Mon, 13/08/2018 - 19:57
Related Articles Non-targeted metabolomics reveals alterations in liver and plasma of gilt-head bream exposed to oxybenzone. Chemosphere. 2018 Aug 04;211:624-631 Authors: Ziarrusta H, Mijangos L, Picart-Armada S, Irazola M, Perera-Lluna A, Usobiaga A, Prieto A, Etxebarria N, Olivares M, Zuloaga O Abstract The extensive use of the organic UV filter oxybenzone has led to its ubiquitous occurrence in the aquatic environment, causing an ecotoxicological risk to biota. Although some studies reported adverse effects, such as reproductive toxicity, further research needs to be done in order to assess its molecular effects and mechanism of action. Therefore, in the present work, we investigated metabolic perturbations in juvenile gilt-head bream (Sparus aurata) exposed over 14 days via the water to oxybenzone (50 mg/L). The non-targeted analysis of brain, liver and plasma extracts was performed by means of UHPLC-qOrbitrap MS in positive and negative modes with both C18 and HILIC separation. Although there was no mortality or alterations in general physiological parameters during the experiment, and the metabolic profile of brain was not affected, the results of this study showed that oxybenzone could perturb both liver and plasma metabolome. The pathway enrichment suggested that different pathways in lipid metabolism (fatty acid elongation, α-linolenic acid metabolism, biosynthesis of unsaturated fatty acids and fatty acid metabolism) were significantly altered, as well as metabolites involved in phenylalanine and tyrosine metabolism. Overall, these changes are signs of possible oxidative stress and energy metabolism modification. Therefore, this research indicates that oxybenzone has adverse effects beyond the commonly studied hormonal activity, and demonstrates the sensitivity of metabolomics to assess molecular-level effects of emerging contaminants. PMID: 30098557 [PubMed - as supplied by publisher]

8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity.

Mon, 13/08/2018 - 19:57
Related Articles 8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with stronger metabolic modulator activity. Toxicol In Vitro. 2018 Aug 08;: Authors: Carrageta DF, Dias TR, Jarak I, Alves MG, Oliveira PF, Van der Walt MM, Terre'Blanche G, Monteiro MP, Silva BM Abstract Caffeine is one of the most worldwide consumed methylxanthines. It is well-known for its thermogenic and cell metabolism modulating effects. Based on methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine (PTX) is a novel adenosine antagonist with higher receptor affinity than caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger than those of caffeine. For that purpose, murine 3 T3-L1 cells were cultured in the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 μM) for 24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and lactate dehydrogenase (LDH) release. Cell metabolites released to the culture medium were identified and quantified by proton nuclear magnetic resonance (1H NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX displayed no signs of cytotoxicity at all studied concentrations. When compared with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as well as lactate, alanine, and acetate production. Additionally, PTX decreased protein oxidation, thus protecting against oxidative stress-induced damage. These results illustrate that PTX is a stronger and less cytotoxic caffeine substitute with potential applications as metabolic modulator and a good candidate for novel drug design. PMID: 30098389 [PubMed - as supplied by publisher]

Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.

Mon, 13/08/2018 - 19:57
Related Articles Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain. Neurochem Int. 2018 Aug 09;120:75-86 Authors: Chitturi J, Li Y, Santhakumar V, Kannurpatti SS Abstract Pathophysiology of developmental traumatic brain injury (TBI) is unique due to intrinsic differences in the developing brain. Energy metabolic studies of the brain during early development (P13 to P30) have indicated acute oxidative energy metabolic decreases below 24 h after TBI, which generally recovered by 48 h. However, marked neurodegeneration and altered neural functional connectivity have been observed at later stages into adolescence. As secondary neurodegeneration is most prominent during the first week after TBI in the rat model, we hypothesized that the subacute TBI-metabolome may contain predictive markers of neurodegeneration. Sham and TBI metabolomes were examined at 72 h after a mild to moderate intensity TBI in male Sprague-Dawley rats aged P31. Sensorimotor behavior was assessed at 24, 48 and 72 h after injury, followed by 72-hour postmortem brain removal for metabolomics using Liquid Chromatography/Mass Spectrometry (LC-MS) measurement. Broad TBI-induced metabolomic shifts occurred with relatively higher intensity in the injury-lateralized (ipsilateral) hemisphere. Intensity of metabolomic perturbation correlated with the extent of sensorimotor behavioral deficit. N-acetyl-aspartate (NAA) levels at 72 h after TBI, predicted the extent of neurodegeneration assessed histochemically 7-days post TBI. Results from the multivariate untargeted approach clearly distinguished metabolomic shifts induced by TBI. Several pathways including amino acid, fatty acid and energy metabolism continued to be affected at 72 h after TBI, whose collective effects may determine the overall pathological response after TBI in early development including neurodegeneration. PMID: 30098378 [PubMed - as supplied by publisher]

Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People.

Mon, 13/08/2018 - 19:57
Related Articles Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People. Mol Nutr Food Res. 2018 Aug 11;:e1800583 Authors: Wei R, Ross AB, Su M, Wang J, Guiraud SP, Draper CF, Beaumont M, Jia W, Martin FP Abstract SCOPE: The objective of this study was to develop a new methodology to identify the relationship between dietary patterns and metabolites indicative of food intake and metabolism. METHODS AND RESULTS: Plasma and urine samples from healthy Swiss subjects (n = 89) collected over two time points were analyzed for a panel of host-microbial metabolites using gas chromatography- and liquid chromatography-mass spectrometry. Dietary intake was evaluated using a validated food frequency questionnaire. Dietary pattern clusters and relationships with metabolites were determined using Non-Negative Matrix Factorization (NNMF) and Sparse Generalized Canonical Correlation Analysis (SGCCA). Use of NNMF allowed detection of latent diet clusters in this population, which described a high intake of meat or vegetables. SGCCA associated these clusters to (i) diet-host microbial and lipid associated bile acid metabolism, and (ii) essential amino acid metabolism. CONCLUSION: This novel application of NNMF and SGCCA allowed detection of distinct metabotypes for meat and vegetable dietary patterns in a heterogeneous population. As many of the metabolites associated with meat or vegetable intake are the result of host-microbiota interactions, the results support a role for microbiota mediating the metabolic imprinting of different dietary choices. This article is protected by copyright. All rights reserved. PMID: 30098305 [PubMed - as supplied by publisher]

NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells.

Mon, 13/08/2018 - 19:57
Related Articles NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and human cells. FEBS J. 2018 Aug 11;: Authors: Becker-Kettern J, Paczia N, Conrotte JF, Zhu C, Fiehn O, Jung PP, Steinmetz LM, Linster CL Abstract NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH cofactors, known to inhibit several dehydrogenases in vitro. A metabolite repair system that is conserved in all domains of life and that comprises the two enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both the S- and R-epimers of NADHX and NADPHX to the normal cofactors. An inherited deficiency in this system has recently been shown to cause severe neurometabolic disease in children. Although evidence for the presence of NAD(P)HX has been obtained in plant and human cells, little is known about the mechanism of formation of these derivatives in vivo and their potential effects on cell metabolism. Here, we show that NAD(P)HX dehydratase deficiency in yeast leads to an important, temperature-dependent NADHX accumulation in quiescent cells with a concomitant depletion of intracellular NAD+ and serine pools. We demonstrate that NADHX potently inhibits the first step of the serine synthesis pathway in yeast. Human cells deficient in the NAD(P)HX dehydratase also accumulated NADHX and showed decreased viability. In addition, those cells consumed more glucose and produced more lactate, potentially indicating impaired mitochondrial function. Our results provide first insights into how NADHX accumulation affects cellular functions and pave the way for a better understanding of the mechanism(s) underlying the rapid and severe neurodegeneration leading to early death in NADHX repair deficient children. This article is protected by copyright. All rights reserved. PMID: 30098110 [PubMed - as supplied by publisher]

Assays for NAD+-Dependent Reactions and NAD+ Metabolites.

Mon, 13/08/2018 - 19:57
Related Articles Assays for NAD+-Dependent Reactions and NAD+ Metabolites. Methods Mol Biol. 2018;1813:77-90 Authors: Schultz MB, Lu Y, Braidy N, Sinclair DA Abstract Nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor and signaling molecule that controls the activity of enzymes involved in metabolism, DNA repair, and cellular survival, such as the PARPs, CD38, and the sirtuins. Here, we describe three methods for measuring the activity of these enzymes: the etheno-NAD+ assay measures NAD+ hydrolase activity using an NAD+ analog to produce a fluorescent product that is measured in real time; the PNC1 assay converts a native product of NAD+ hydrolysis, nicotinamide, into a quantitative fluorescent readout; and liquid chromatography tandem mass spectrometry (LC-MS/MS) is used to characterize the entire NAD+ metabolome in a sample. These methods will enable new insights into the roles that NAD+ and the enzymes that utilize it play in health and disease. PMID: 30097862 [PubMed - in process]

Characterization of oil-producing yeast Lipomyces starkeyi on glycerol carbon source based on metabolomics and 13C-labeling.

Mon, 13/08/2018 - 19:57
Related Articles Characterization of oil-producing yeast Lipomyces starkeyi on glycerol carbon source based on metabolomics and 13C-labeling. Appl Microbiol Biotechnol. 2018 Aug 10;: Authors: Maruyama Y, Toya Y, Kurokawa H, Fukano Y, Sato A, Umemura H, Yamada K, Iwasaki H, Tobori N, Shimizu H Abstract Lipomyces starkeyi is an oil-producing yeast that can produce triacylglycerol (TAG) from glycerol as a carbon source. The TAG was mainly produced after nitrogen depletion alongside reduced cell proliferation. To obtain clues for enhancing the TAG production, cell metabolism during the TAG-producing phase was characterized by metabolomics with 13C labeling. The turnover analysis showed that the time constants of intermediates from glycerol to pyruvate (Pyr) were large, whereas those of tricarboxylic acid (TCA) cycle intermediates were much smaller than that of Pyr. Surprisingly, the time constants of intermediates in gluconeogenesis and the pentose phosphate (PP) pathway were large, suggesting that a large amount of the uptaken glycerol was metabolized via the PP pathway. To synthesize fatty acids that make up TAG from acetyl-CoA (AcCoA), 14 molecules of nicotinamide adenine dinucleotide phosphate (NADPH) per C16 fatty acid molecule are required. Because the oxidative PP pathway generates NADPH, this pathway would contribute to supply NADPH for fatty acid synthesis. To confirm that the oxidative PP pathway can supply the NADPH required for TAG production, flux analysis was conducted based on the measured specific rates and mass balances. Flux analysis revealed that the NADPH necessary for TAG production was supplied by metabolizing 48.2% of the uptaken glycerol through gluconeogenesis and the PP pathway. This result was consistent with the result of the 13C-labeling experiment. Furthermore, comparison of the actual flux distribution with the ideal flux distribution for TAG production suggested that it is necessary to flow more dihydroxyacetonephosphate (DHAP) through gluconeogenesis to improve TAG yield. PMID: 30097695 [PubMed - as supplied by publisher]

Integrative analysis of fitness and metabolic effects of plasmids in Pseudomonas aeruginosa PAO1.

Mon, 13/08/2018 - 19:57
Related Articles Integrative analysis of fitness and metabolic effects of plasmids in Pseudomonas aeruginosa PAO1. ISME J. 2018 Aug 10;: Authors: San Millan A, Toll-Riera M, Qi Q, Betts A, Hopkinson RJ, McCullagh J, MacLean RC Abstract Horizontal gene transfer (HGT) mediated by the spread of plasmids fuels evolution in prokaryotes. Although plasmids provide bacteria with new adaptive genes, they also produce physiological alterations that often translate into a reduction in bacterial fitness. The fitness costs associated with plasmids represent an important limit to plasmid maintenance in bacterial communities, but their molecular origins remain largely unknown. In this work, we combine phenomics, transcriptomics and metabolomics to study the fitness effects produced by a collection of diverse plasmids in the opportunistic pathogen Pseudomonas aeruginosa PAO1. Using this approach, we scan the physiological changes imposed by plasmids and test the generality of some main mechanisms that have been proposed to explain the cost of HGT, including increased biosynthetic burden, reduced translational efficiency, and impaired chromosomal replication. Our results suggest that the fitness effects of plasmids have a complex origin, since none of these mechanisms could individually provide a general explanation for the cost of plasmid carriage. Interestingly, our results also showed that plasmids alter the expression of a common set of metabolic genes in PAO1, and produce convergent changes in host cell metabolism. These surprising results suggest that there is a common metabolic response to plasmids in P. aeruginosa PAO1. PMID: 30097663 [PubMed - as supplied by publisher]

Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours.

Mon, 13/08/2018 - 19:57
Related Articles Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours. Sci Rep. 2018 Aug 10;8(1):11992 Authors: Bennett CD, Kohe SE, Gill SK, Davies NP, Wilson M, Storer LCD, Ritzmann T, Paine SML, Scott IS, Nicklaus-Wollenteit I, Tennant DA, Grundy RG, Peet AC Abstract Paediatric brain tumors are becoming well characterized due to large genomic and epigenomic studies. Metabolomics is a powerful analytical approach aiding in the characterization of tumors. This study shows that common cerebellar tumors have metabolite profiles sufficiently different to build accurate, robust diagnostic classifiers, and that the metabolite profiles can be used to assess differences in metabolism between the tumors. Tissue metabolite profiles were obtained from cerebellar ependymoma (n = 18), medulloblastoma (n = 36), pilocytic astrocytoma (n = 24) and atypical teratoid/rhabdoid tumors (n = 5) samples using HR-MAS. Quantified metabolites accurately discriminated the tumors; classification accuracies were 94% for ependymoma and medulloblastoma and 92% for pilocytic astrocytoma. Using current intraoperative examination the diagnostic accuracy was 72% for ependymoma, 90% for medulloblastoma and 89% for pilocytic astrocytoma. Elevated myo-inositol was characteristic of ependymoma whilst high taurine, phosphocholine and glycine distinguished medulloblastoma. Glutamine, hypotaurine and N-acetylaspartate (NAA) were increased in pilocytic astrocytoma. High lipids, phosphocholine and glutathione were important for separating ATRTs from medulloblastomas. This study demonstrates the ability of metabolic profiling by HR-MAS on small biopsy tissue samples to characterize these tumors. Analysis of tissue metabolite profiles has advantages in terms of minimal tissue pre-processing, short data acquisition time giving the potential to be used as part of a rapid diagnostic work-up. PMID: 30097636 [PubMed - in process]

Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease.

Mon, 13/08/2018 - 19:57
Related Articles Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic target for sickle cell disease. Blood Adv. 2018 Aug 14;2(15):1957-1968 Authors: Liu H, Adebiyi M, Liu RR, Song A, Manalo J, Wen YE, Wen AQ, Weng T, Ko J, Idowu M, Kellems RE, Eltzschig HK, Blackburn MR, Juneja HS, Xia Y Abstract Although excessive plasma adenosine is detrimental in sickle cell disease (SCD), the molecular mechanism underlying elevated circulating adenosine remains unclear. Here we report that the activity of soluble CD73, an ectonucleotidase producing extracellular adenosine, was significantly elevated in a murine model of SCD and correlated with increased plasma adenosine. Mouse genetic studies demonstrated that CD73 activity contributes to excessive induction of plasma adenosine and thereby promotes sickling, hemolysis, multiorgan damage, and disease progression. Mechanistically, we showed that erythrocyte adenosine 5'-monophosphate-activated protein kinase (AMPK) was activated both in SCD patients and in the murine model of SCD. AMPK functions downstream of adenosine receptor ADORA2B signaling and contributes to sickling by regulating the production of erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric regulator of hemoglobin-O2 binding affinity. Preclinically, we reported that treatment of α,β-methylene adenosine 5'-diphosphate, a potent CD73 specific inhibitor, significantly decreased sickling, hemolysis, multiorgan damage, and disease progression in the murine model of SCD. Taken together, both human and mouse studies reveal a novel molecular mechanism contributing to the pathophysiology of SCD and identify potential therapeutic strategies to treat SCD. PMID: 30097462 [PubMed - in process]

Application of Electronic-Nose Technologies and VOC-Biomarkers for the Noninvasive Early Diagnosis of Gastrointestinal Diseases †.

Mon, 13/08/2018 - 19:57
Related Articles Application of Electronic-Nose Technologies and VOC-Biomarkers for the Noninvasive Early Diagnosis of Gastrointestinal Diseases †. Sensors (Basel). 2018 Aug 09;18(8): Authors: Wilson AD Abstract Conventional methods utilized for clinical diagnosis of gastrointestinal (GI) diseases have employed invasive medical procedures that cause stress, anxiety and pain to patients. These methods are often expensive, time-consuming, and require sophisticated chemical-analysis instruments and advanced modeling procedures to achieve diagnostic interpretations. This paper reviews recent applications of simpler, electronic-nose (e-nose) devices for the noninvasive early diagnosis of a wide range of GI diseases by collective analysis of headspace volatile organic compound (VOC)-metabolites from clinical samples to produce disease-specific aroma signatures (VOC profiles). A different "metabolomics" approach to GI disease diagnostics, involving identifications and quantifications of disease VOC-metabolites, are compared to the electronic-nose approach based on diagnostic costs, accuracy, advantages and disadvantages. The importance of changes in gut microbiome composition that result from disease are discussed relative to effects on disease detection. A new diagnostic approach, which combines the use of e-nose instruments for early rapid prophylactic disease-screenings with targeted identification of known disease biomarkers, is proposed to yield cheaper, quicker and more dependable diagnostic results. Some priority future research needs and coordination for bringing e-nose instruments into routine clinical practice are summarized. PMID: 30096939 [PubMed - in process]

Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper (Piper nigrum L.) Products Based on LC-MS/MS Analysis.

Mon, 13/08/2018 - 19:57
Related Articles Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper (Piper nigrum L.) Products Based on LC-MS/MS Analysis. Molecules. 2018 Aug 09;23(8): Authors: Gu F, Wu G, Fang Y, Zhu H Abstract In the present study, nontargeted metabolomics was used to screen the phenolic and polyhydroxy compounds in pepper products. A total of 186 phenolic and polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl quinic acid O-hexoside, quinic acid (polyhydroxy compounds), etc. For the selected 50 types of phenolic compound, except malvidin 3,5-diglucoside (malvin), l-epicatechin and 4'-hydroxy-5,7-dimethoxyflavanone, other compound contents were present in high contents in freeze-dried pepper berries, and pinocembrin was relatively abundant in two kinds of pepper products. The score plots of principal component analysis indicated that the pepper samples can be classified into four groups on the basis of the type pepper processing. This study provided a comprehensive profile of the phenolic and polyhydroxy compounds of different pepper products and partly clarified the factors responsible for different metabolite profiles in ongoing studies and the changes of phenolic compounds for the browning mechanism of black pepper. PMID: 30096911 [PubMed - in process]

metabolomics; +21 new citations

Sat, 11/08/2018 - 15:40
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +21 new citations

Sat, 11/08/2018 - 12:36
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Fri, 10/08/2018 - 15:14
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +16 new citations

Fri, 10/08/2018 - 12:13
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/08/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Characteristics of Colon-Derived Uremic Solutes.

Thu, 09/08/2018 - 14:51
Related Articles Characteristics of Colon-Derived Uremic Solutes. Clin J Am Soc Nephrol. 2018 Aug 07;: Authors: Mair RD, Sirich TL, Plummer NS, Meyer TW Abstract BACKGROUND AND OBJECTIVES: Colon microbial metabolism produces solutes that are normally excreted in the urine and accumulate in the plasma when the kidneys fail. This study sought to further identify and characterize human colon-derived uremic solutes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Colon-derived solutes normally excreted in the urine were identified by comparing urine from controls (n=17) and patients with total colectomies (n=12), using an established metabolomic platform. Colon-derived solutes that accumulate in kidney failure were then identified by comparing the plasma of the control patients with that of patients on dialysis (n=14). RESULTS: Ninety-one urinary solutes were classified as colon-derived on the basis of the finding of a urine excretion rate at least four-fold higher in control patients than in patients with total colectomies. Forty-six were solutes with known chemical structure, 35 of which had not previously been identified as colon-derived. Sixty of the colon-derived solutes accumulated in the plasma of patients with ESKD to a degree greater than urea and were therefore classified as uremic. The estimated urinary clearance for 27 out of the 32 colon-derived solutes for which clearance could be calculated exceeded that of creatinine, consistent with tubular secretion. Sulfatase treatment revealed that 42 out of the 91 colon-derived solutes detected were likely conjugates. CONCLUSIONS: Metabolomic analysis identified numerous colon-derived solutes that are normally excreted in human urine. Clearance by tubular secretion limits plasma levels of many colon-derived solutes. PMID: 30087103 [PubMed - as supplied by publisher]

Gut-Derived Metabolites and Chronic Kidney Disease: The Forest (F)or the Trees?

Thu, 09/08/2018 - 14:51
Related Articles Gut-Derived Metabolites and Chronic Kidney Disease: The Forest (F)or the Trees? Clin J Am Soc Nephrol. 2018 Aug 07;: Authors: Vanholder R, Glorieux G PMID: 30087101 [PubMed - as supplied by publisher]

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