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

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PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 19 min 22 sec ago

UPLC/MS-Based Metabolomics Investigation of the Protective Effect of Hydrogen Gas Inhalation on Mice with Calcium Oxalate-Induced Renal Injury.

Fri, 02/11/2018 - 12:00
Related Articles UPLC/MS-Based Metabolomics Investigation of the Protective Effect of Hydrogen Gas Inhalation on Mice with Calcium Oxalate-Induced Renal Injury. Biol Pharm Bull. 2018;41(11):1652-1658 Authors: Lu H, Ding J, Liu W, Peng Z, Chen W, Sun X, Guo Z Abstract Hydrogen has a significant protective effect on calcium oxalate-induced renal injury, but its effect on metabolic profiles is unknown. This study showed the effects of hydrogen on serum and urine metabolites in a renal injury model. Ultra-HPLC quadrupole time-of-flight-MS-based metabolomics was used to characterise metabolic variations. Twenty-five serum metabolites and 14 urine metabolites showed differences in the the nitrogen and oxygen inhalation (NO), nitrogen and oxygen inhalation combined with calcium oxalate induction (CaOx), and hydrogen inhalation combined with calcium oxalate induction (HO+CaOx) groups. Nineteen serum metabolites and 7 urine metabolites showed significant restoration to normal levels after hydrogen gas (H2) treatment. These metabolites are primarily related to amino acid metabolism, fatty acid metabolism, and phospholipid metabolism. This study showed that a comprehensive metabolomics approach is an effective strategy to elucidate the mechanisms underlying the effects of hydrogen treatment on calcium oxalate-induced renal injury. PMID: 30381664 [PubMed - in process]

Erratum for Hardison et al., "Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development".

Fri, 02/11/2018 - 12:00
Related Articles Erratum for Hardison et al., "Transient Nutrient Deprivation Promotes Macropinocytosis-Dependent Intracellular Bacterial Community Development". mSphere. 2018 Oct 31;3(5): Authors: Hardison RL, Heimlich DR, Harrison A, Beatty WL, Rains S, Moseley MA, Thompson JW, Justice SS, Mason KM PMID: 30381357 [PubMed - in process]

Hydrophilic interaction liquid chromatography coupled with quadrupole-orbitrap ultra high resolution mass spectrometry to quantitate nucleobases, nucleosides, and nucleotides during white tea withering process.

Fri, 02/11/2018 - 12:00
Related Articles Hydrophilic interaction liquid chromatography coupled with quadrupole-orbitrap ultra high resolution mass spectrometry to quantitate nucleobases, nucleosides, and nucleotides during white tea withering process. Food Chem. 2018 Nov 15;266:343-349 Authors: Zhao F, Qiu X, Ye N, Qian J, Wang D, Zhou P, Chen M Abstract Nucleotides, nucleosides, and nucleobases are important bioactive compounds. Recent studies suggested that they possess taste activity. However, it remains unknown about their presence in white tea and how they change during white tea manufacture. Here, we first established method based on hydrophilic interaction liquid chromatography coupled with quadrupole-orbitrap ultra high resolution mass spectrometry (HILIC-Quadrupole-Orbitrap-UHRMS) platform, then applied it to study the dynamic changes of nucleotides, nucleosides, and nucleobases during white tea withering process. Five compounds, including adenosine 5'-monophosphate monohydrate (AMP), guanosine 5'-monophosphate disodium salt hydrate (GMP), adenosine, cytidine, thymine and uracil, were detected from withering samples. They showed a general decline trend during white tea withering process, however, considerable amount of them was retained after withering for 48 h except adenosine which was below detection limit after withering for 21 h. This study provided a complete picture about nucleotides, nucleosides and nucleobases changes during white tea withering process. PMID: 30381196 [PubMed - in process]

Untargeted metabolite profiling for koji-fermentative bioprocess unravels the effects of varying substrate types and microbial inocula.

Fri, 02/11/2018 - 12:00
Related Articles Untargeted metabolite profiling for koji-fermentative bioprocess unravels the effects of varying substrate types and microbial inocula. Food Chem. 2018 Nov 15;266:161-169 Authors: Seo HS, Lee S, Singh D, Shin HW, Cho SA, Lee CH Abstract Untargeted metabolomics unraveled the effects of varying substrates (soybean, wheat, and rice) and inocula (Aspergillus oryzae and Bacillus amyloliquefaciens) on metabolite compositions of koji, a starter ingredient in various Asian fermented foods. Multivariate analyses of the hyphenated mass spectrometry datasets for different koji extracts highlighted 61 significantly discriminant primary metabolites (sugars and sugar alcohols, organic acids, amino acids, fatty acids, nucleosides, phenolic acids, and vitamins) according to varying substrates and inocula combinations. However, 59 significantly discriminant secondary metabolites were evident for koji-types with varying substrates only, viz., soybean (flavonoids, soyasaponins, and lysophospholipids), wheat (flavones and lysophospholipids), and rice (flavonoids, fatty acids derivatives, and lysophospholipids). Independently, the substrates influenced primary metabolite compositions in koji (soybean > wheat, rice). The inocula choice of A. oryzae engendered higher carbohydrates, organic acids, and lipid derivative levels commensurate with high α-amylase and β-glucosidase activities, while B. amyloliquefaciens affected higher amino acids levels, in respective koji types. PMID: 30381171 [PubMed - in process]

Metabolic and proteomic responses to long-term protein restriction in a pig model.

Fri, 02/11/2018 - 12:00
Related Articles Metabolic and proteomic responses to long-term protein restriction in a pig model. J Agric Food Chem. 2018 Nov 01;: Authors: Li Y, Yin J, Han H, Liu G, Deng D, Kim SW, Wu G, Li T, Yin Y Abstract Protein restriction is associated with extended lifespan and reduced incidence and progression of multiple age-related diseases. The underlying mechanism of metabolic and proteomic responses to the long-term dietary protein restriction, however, has not been fully uncovered. The present study aimed to identify the metabolic and proteomic profiles in a low-protein diet-fed pig model. Intestinal and liver metabolomics showed that amino acid metabolism was highly associated with dietary protein restriction. Interestingly, blood was characterized by markedly higher abundances of Ser, Gly, Glu, Thr, Ala, Lys, and Met levels, and lower abundances of His, Val, and Ile levels regardless of the age of pigs from piglets to adult pigs. Amino acid transporters might contribute to the changed amino acid pools and serve as a feedback regulatory mechanism in response to protein restriction. iTRAQ-based quantitative proteomics approach identified more than 10 differently expressed proteins in protein restricted pigs and KEGG pathway analysis showed that significant enrichment of proteins involved in metabolic pathways, PI3K-Akt signaling pathway, lysosome, spliceosome, oxidative phosphorylation, phagosome, and DNA replication. Western blot analysis further confirmed that protein restriction markedly inactivated Akt and mTOR signals in pigs. This study indicates that dietary protein restriction leads to a shift in the host metabolism in a pig model, especially for amino acid metabolism. Along with proteomics, our findings unveil potential mechanisms for integrating how protein restriction modulates host metabolism. PMID: 30380847 [PubMed - as supplied by publisher]

Investigation into Cellular Glycolysis for the Mechanism Study of Energy Metabolism Disorder Triggered by Lipopolysaccharide.

Fri, 02/11/2018 - 12:00
Related Articles Investigation into Cellular Glycolysis for the Mechanism Study of Energy Metabolism Disorder Triggered by Lipopolysaccharide. Toxins (Basel). 2018 Oct 29;10(11): Authors: Zhang R, Ji J, Blaženović I, Pi F, Wang T, Zhang Y, Sun X Abstract Lipopolysaccharide (LPS) is the main virulence factor of Gram-negative bacteria, which can incite inflammation in tissues by inducing cells to secrete a variety of proinflammatory mediators, including cytokines, chemokines, interleukins, and prostaglandins. Herein, we chose LPS as an inducer to establish an inflammatory model of HeLa cells, and explored the effects of LPS on energy metabolism. We treated HeLa cells with different concentrations (0, 0.4, 1.0, 2.0, 4.0, and 6.0 μg/mL) of LPS for 24 h, and explored its effects on intercellular adenosine triphosphate (ATP) levels, intercellular nitrous oxide (NO) content, mitochondrial functions, and enzyme activities related to energy metabolism. Furthermore, we used metabonomics to study the metabolites that participated in energy metabolism. We found a positive correlation between LPS concentrations and intracellular ATP levels. In addition, LPS increased intracellular NO production, altered mitochondrial functions, strengthened glycolytic enzyme activities, and changed metabolites related to energy metabolism. Hence, in this study, we showed that LPS can strengthen energy metabolism by enhancing glycolysis, which could be used as an early diagnostic biomarker or a novel therapeutic target for inflammation-associated cancers. PMID: 30380670 [PubMed - in process]

Metabonomic profiling of chronic intermittent hypoxia in a mouse model.

Fri, 02/11/2018 - 12:00
Related Articles Metabonomic profiling of chronic intermittent hypoxia in a mouse model. Respir Physiol Neurobiol. 2018 10;256:157-173 Authors: Conotte S, Tassin A, Conotte R, Colet JM, Zouaoui Boudjeltia K, Legrand A Abstract Chronic intermittent hypoxia (ChIH) is a dominant feature of obstructive sleep apnoea (OSA) and is associated to metabolic alterations and oxidative stress (OS). Although management of OSA is well established, the research of new biomarkers that are independent of confounding factors remains necessary to improve the early detection of comorbidity and therapeutic follow-up. In this study, the urinary metabonomic profile associated to intermittent hypoxia was evaluated in a mouse model. When exposed to intermittent hypoxia, animals showed a significant alteration in energy metabolism towards anaerobic pathways and signs of OS imbalance. A compensatory response was observed over time. Our data also indicates an excess production of vitamin B3, liver function modulations and a stimulation of creatine synthesis which could be used to evaluate the ChIH repercussions. As well, TMAO and allantoin could constitute interesting biomarker candidates, respectively in the context of cardiovascular risk and OS associated to OSA. PMID: 29522877 [PubMed - indexed for MEDLINE]

Plasma metabolomics of children with aberrant serum lipids and inadequate micronutrient intake.

Thu, 01/11/2018 - 11:44
Plasma metabolomics of children with aberrant serum lipids and inadequate micronutrient intake. PLoS One. 2018;13(10):e0205899 Authors: Li KJ, Jenkins N, Luckasen G, Rao S, Ryan EP Abstract Blood lipids have served as key biomarkers for cardiovascular disease (CVD) risk, yet emerging evidence indicates metabolite profiling might reveal a larger repertoire of small molecules that reflect altered metabolism, and which may be associated with early disease risk. Inadequate micronutrient status may also drive or exacerbate CVD risk factors that emerge during childhood. This study aimed to understand relationships between serum lipid levels, the plasma metabolome, and micronutrient status in 38 children (10 ± 0.8 years) at risk for CVD. Serum lipid levels were measured via autoanalyzer and average daily micronutrient intakes were calculated from 3-day food logs. Plasma metabolites were extracted using 80% methanol and analyzed via ultra-high-performance liquid chromatography-tandem mass spectrometry. Spearman's rank-order coefficients (rs) were computed for correlations between the following serum lipids [total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG)], 805 plasma metabolites, and 17 essential micronutrients. Serum lipid levels in the children ranged from 128-255 mg/dL for total cholesterol, 67-198 mg/dL for LDL, 31-58 mg/dL for HDL, and 46-197 mg/dL for TG. The majority of children (71 to 100%) had levels lower than the Recommended Daily Allowance for vitamin E, calcium, magnesium, folate, vitamin D, and potassium. For sodium, 76% of children had levels above the Upper Limit of intake. Approximately 30% of the plasma metabolome (235 metabolites) were significantly correlated with serum lipids. As expected, plasma cholesterol was positively correlated with serum total cholesterol (rs = 0.6654; p<0.0001). Additionally, 27 plasma metabolites were strongly correlated with serum TG (rs ≥0.60; p≤0.0001), including alanine and diacylglycerols, which have previously been associated with cardiometabolic and atherosclerotic risk in adults and experimental animals. Plasma metabolite profiling alongside known modifiable risk factors for children merit continued investigation in epidemiological studies to assist with early CVD detection, mitigation, and prevention via lifestyle-based interventions. PMID: 30379930 [PubMed - in process]

Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model.

Thu, 01/11/2018 - 11:44
Scaled traumatic brain injury results in unique metabolomic signatures between gray matter, white matter, and serum in a piglet model. PLoS One. 2018;13(10):e0206481 Authors: Baker EW, Henderson WM, Kinder HA, Hutcheson JM, Platt SR, West FD Abstract Traumatic brain injury (TBI) is a leading cause of death and long-term disability in the United States. The heterogeneity of the disease coupled with the lack of comprehensive, standardized scales to adequately characterize multiple types of TBI remain to be major challenges facing effective therapeutic development. A systems level approach to TBI diagnosis through the use of metabolomics could lead to a better understanding of cellular changes post-TBI and potential therapeutic targets. In the current study, we utilize a GC-MS untargeted metabolomics approach to demonstrate altered metabolism in response to TBI in a translational pig model, which possesses many neuroanatomical and pathophysiologic similarities to humans. TBI was produced by controlled cortical impact (CCI) in Landrace piglets with impact velocity and depth of depression set to 2m/s;6mm, 4m/s;6mm, 4m/s;12mm, or 4m/s;15mm resulting in graded neural injury. Serum samples were collected pre-TBI, 24 hours post-TBI, and 7 days post-TBI. Partial least squares discriminant analysis (PLS-DA) revealed that each impact parameter uniquely influenced the metabolomic profile after TBI, and gray and white matter responds differently to TBI on the biochemical level with evidence of white matter displaying greater metabolic change. Furthermore, pathway analysis revealed unique metabolic signatures that were dependent on injury severity and brain tissue type. Metabolomic signatures were also detected in serum samples which potentially captures both time after injury and injury severity. These findings provide a platform for the development of a more accurate TBI classification scale based unique metabolomic signatures. PMID: 30379914 [PubMed - in process]

Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study.

Thu, 01/11/2018 - 11:44
Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study. Crit Care Med. 2018 Oct 30;: Authors: Chung KP, Chen GY, Chuang TY, Huang YT, Chang HT, Chen YF, Liu WL, Chen YJ, Hsu CL, Huang MT, Kuo CH, Yu CJ Abstract OBJECTIVES: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. DESIGN: Prospective multicenter cohort studies with derivation and validation cohort design. SETTING: ICUs at two medical centers and three regional hospitals in Taiwan. PATIENTS: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. INTERVENTIONS: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. MEASUREMENTS AND MAIN RESULTS: In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (≥ 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340-11.975; p < 0.001 by Cox proportional hazard model). CONCLUSIONS: We confirm that plasma acetylcarnitine can reflect the severity of organ dysfunction, inflammation, and infection in sepsis and can serve as a prognostic biomarker for mortality prediction. PMID: 30379669 [PubMed - as supplied by publisher]

Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury.

Thu, 01/11/2018 - 11:44
Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury. Am J Physiol Renal Physiol. 2018 Oct 31;: Authors: Izquierdo-Garcia JL, Nin N, Cardinal-Fernandez P, Rojas Y, de Paula M, Granados R, Martínez-Caro L, Ruiz-Cabello J, Lorente JÁ Abstract The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure (MPAP), renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t=0 min by the administration of live Escherichia coli (n=6) or saline (n=8). At t=300 min, animals were sacrificed. Renal tissue, urine and serum samples were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. Principal component analyses were performed on the processed NMR spectra to highlight kidney injury biomarkers. Sepsis was associated with decreased QT and MAP, and decreased QRA, QRC and urine output. Creatinine serum concentration and neutrophil gelatinase-associated lipocalin serum and urine concentrations increased. NMR-based metabolomics analysis found metabolic differences between control and septic animals: (i) in kidney tissue, increased lactate and nicotinuric acid, and decreased valine, aspartate, glucose and threonine; (ii) in urine, increased isovaleroglycine, aminoadipic acid, N-acetylglutamine, N-acetylaspartate and ascorbic acid, and decreased myoinositol and phenylacetylglycine; (iii) in serum, increased lactate, alanine, pyruvate and glutamine, and decreased valine, glucose and betaine concentrations. The concentration of several metabolites altered in renal tissue and urine samples from septic animals showed a significant correlation with markers of AKI (i.e., creatinine and NGAL serum concentrations). NMR-based metabolomics is a potentially useful tool for biomarker identification of sepsis-induced AKI. PMID: 30379100 [PubMed - as supplied by publisher]

Flow Injection-Traveling Wave Ion Mobility-Mass Spectrometry for Rapid Prostate Cancer Metabolomics.

Thu, 01/11/2018 - 11:44
Flow Injection-Traveling Wave Ion Mobility-Mass Spectrometry for Rapid Prostate Cancer Metabolomics. Anal Chem. 2018 Oct 31;: Authors: Zang X, Monge ME, Gaul DA, Fernandez FM Abstract Flow injection-traveling wave ion mobility-mass spectrometry (FI-TWIM-MS) was applied to the non-targeted metabolic profiling of serum extracts from 61 prostate cancer (PCa) patients and 42 controls with an analysis speed of 6 minutes per sample, including a wash run. Comprehensive data mining of the mobility-mass domain was used to discriminate species with various charge states and filter matrix salt cluster ions. Specific criteria were developed to ensure correct grouping of adducts, in-source fragments, and impurities in the dataset. Endogenous metabolites were identified with high confidence using FI-TWIM-MS/MS and collision cross-section (CCS) matching with chemical standards or CCS databases. PCa patient samples were distinguished from control samples with good accuracies (88.3-89.3%), sensitivities (88.5-90.2%), and specificities (88.1%) using supervised multivariate classification methods. Although largely underutilized in metabolomics studies, FI-TWIM-MS proved advantageous in terms of analysis speed, separation of ions in complex mixtures, improved signal-to-noise ratio, and reduction of spectral congestion. Results from this study showcase the potential of FI-TWIM-MS as a high throughput metabolic profiling tool for large scale metabolomics studies. PMID: 30379062 [PubMed - as supplied by publisher]

The protective effects of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism.

Thu, 01/11/2018 - 11:44
The protective effects of Poria cocos-derived polysaccharide CMP33 against IBD in mice and its molecular mechanism. Food Funct. 2018 Oct 31;: Authors: Liu X, Yu X, Xu X, Zhang X, Zhang X Abstract In this study, the protective effects of a carboxymethyl polysaccharide CMP33 from Poria cocos against inflammatory bowel disease (IBD) were investigated using TNBS-induced colitis in mice. The results showed that CMP33 markedly ameliorated the severity of colitis, including a 2-fold decrease in the mortality rate, a 50% decrease in disease activity index, and a 36%-44% decrease in macro- or microscopic histopathological score, compared with TNBS administration. Moreover, CMP33 decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokines in the colon tissue and serum of colitic mice. Using iTRAQ-coupled- nano-HPLC-MS/MS-based proteomics, the protein profiles after TNBS, high- or low-dose CMP33 and salazosulfapyridine (SASP) treatments were compared and many differentially expressed proteins were identified. Among them, 7 proteins (Hmgcs2, Fabp2, Hp, B4galnt2, B3gnt6, Sap and Ca1) were proposed to be the common targeting protein group (TPG) of CMP33 and drug SASP. Particularly, some targeting proteins were CMP33-dose-specific: high-dose-specific TPG (Mtco3, Gal-6, Mptx, S100 g and Hpx) and low-dose-specific TPG (Zg16, Hexb, Insl5, Cept1, Hspb6 and Ifi27l2b), suggesting the complex acting mechanism of CMP33. GC-TOF-MS-based metabolomics revealed that oleic acid and dihydrotestosterone could be the common targets of CMP33 and SASP. By integrative analysis of proteomics and metabolomics, key protein-metabolite pathways (PMP) were identified, PMP for high-dose: 2-hydroxybutyric acid - (GPT, GGH) - glutathione - ALB - testosterone - TTR - dihydrotestosterone; PMP for low-dose: (PYY, FABP2, HMGCS2) - oleic acid - TTR - dihydrotestosterone. In total, these results demonstrated the protective effects of CMP33 against IBD in mice through the potential TPG and PMP. PMID: 30378628 [PubMed - as supplied by publisher]

Nanoparticle microarray for high-throughput microbiome metabolomics using matrix-assisted laser desorption ionization mass spectrometry.

Thu, 01/11/2018 - 11:44
Nanoparticle microarray for high-throughput microbiome metabolomics using matrix-assisted laser desorption ionization mass spectrometry. Anal Bioanal Chem. 2018 Oct 30;: Authors: Hansen RL, Dueñas ME, Looft T, Lee YJ Abstract A high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI)-MS-based metabolomics platform was developed using a pre-fabricated microarray of nanoparticles and organic matrices. Selected organic matrices, inorganic nanoparticle (NP) suspensions, and sputter coated metal NPs, as well as various additives, were tested for metabolomics analysis of the turkey gut microbiome. Four NPs and one organic matrix were selected as the optimal matrix set: α-cyano-4-hydroycinnamic acid, Fe3O4 and Au NPs in positive ion mode with 10 mM sodium acetate, and Cu and Ag NPs in negative ion mode with no additive. Using this set of five matrices, over two thousand unique metabolite features were reproducibly detected across intestinal samples from turkeys fed a diet amended with therapeutic or sub-therapeutic antibiotics (200 g/ton or 50 g/ton bacitracin methylene disalicylate (BMD), respectively), or non-amended feed. Among the thousands of unique features, 56 of them were chemically identified using MALDI-MS/MS, with the help of in-parallel liquid chromatography (LC)-MS/MS analysis. Lastly, as a proof of concept application, this protocol was applied to 52 turkey cecal samples at three different time points from the antibiotic feed trial. Statistical analysis indicated variations in the metabolome of turkeys with different ages or treatments. Graphical abstract ᅟ. PMID: 30377739 [PubMed - as supplied by publisher]

Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice.

Thu, 01/11/2018 - 11:44
Identification of TMAO-producer phenotype and host-diet-gut dysbiosis by carnitine challenge test in human and germ-free mice. Gut. 2018 Oct 30;: Authors: Wu WK, Chen CC, Liu PY, Panyod S, Liao BY, Chen PC, Kao HL, Kuo HC, Kuo CH, Chiu THT, Chen RA, Chuang HL, Huang YT, Zou HB, Hsu CC, Chang TY, Lin CL, Ho CT, Yu HT, Sheen LY, Wu MS Abstract OBJECTIVE: The gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance. DESIGN: A pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation. RESULTS: The OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecal CntA gene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT. CONCLUSION: The OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment. TRIAL REGISTRATION NUMBER: NCT02838732; Results. PMID: 30377191 [PubMed - as supplied by publisher]

Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers.

Thu, 01/11/2018 - 11:44
Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers. Genome Med. 2018 Oct 31;10(1):78 Authors: Hale VL, Jeraldo P, Chen J, Mundy M, Yao J, Priya S, Keeney G, Lyke K, Ridlon J, White BA, French AJ, Thibodeau SN, Diener C, Resendis-Antonio O, Gransee J, Dutta T, Petterson XM, Sung J, Blekhman R, Boardman L, Larson D, Nelson H, Chia N Abstract BACKGROUND: Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their role in carcinogenesis remain an active area of inquiry. Our understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology. METHODS: We collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Mismatch repair (MMR) status was determined in each tumor sample and classified as either deficient MMR (dMMR) or proficient MMR (pMMR) tumor subtypes. Samples underwent 16S rRNA gene sequencing and a subset of samples from 50 individuals were submitted for targeted metabolomic analysis to quantify amino acids and short-chain fatty acids. A PERMANOVA was used to identify the biological variables that explained variance within the microbial communities. dMMR and pMMR microbial communities were then analyzed separately using a generalized linear mixed effects model that accounted for MMR status, sample location, intra-subject variability, and read depth. Genome-scale metabolic models were then used to generate microbial interaction networks for dMMR and pMMR microbial communities. We assessed global network properties as well as the metabolic influence of each microbe within the dMMR and pMMR networks. RESULTS: We demonstrate distinct roles for microbes in dMMR and pMMR CRC. Bacteroides fragilis and sulfidogenic Fusobacterium nucleatum were significantly enriched in dMMR CRC, but not pMMR CRC. These findings were further supported by metabolic modeling and metabolomics indicating suppression of B. fragilis in pMMR CRC and increased production of amino acid proxies for hydrogen sulfide in dMMR CRC. CONCLUSIONS: Integrating tumor biology and microbial ecology highlighted distinct microbial, metabolic, and ecological properties unique to dMMR and pMMR CRC. This approach could critically improve our ability to define, predict, prevent, and treat colorectal cancers. PMID: 30376889 [PubMed - in process]

Progress in Metabonomics of Type 2 Diabetes Mellitus.

Thu, 01/11/2018 - 11:44
Related Articles Progress in Metabonomics of Type 2 Diabetes Mellitus. Molecules. 2018 Jul 23;23(7): Authors: Ma Q, Li Y, Wang M, Tang Z, Wang T, Liu C, Wang C, Zhao B Abstract With the improvement of living standards and a change in lifestyle, the incidence of type 2 diabetes mellitus (T2DM) is increasing. Its etiology is too complex to be completely understand yet. Metabonomics techniques are used to study the changes of metabolites and metabolic pathways before and after the onset of diabetes and make it more possible to further understand the pathogenesis of T2DM and improve its prediction, early diagnosis, and treatment. In this review, we summarized the metabonomics study of T2DM in recent years and provided a theoretical basis for the study of pathogenesis and the effective prevention and treatment of T2DM. PMID: 30041493 [PubMed - indexed for MEDLINE]

The interaction between the proliferating macroalga Asparagopsis taxiformis and the coral Astroides calycularis induces changes in microbiome and metabolomic fingerprints.

Thu, 01/11/2018 - 11:44
Related Articles The interaction between the proliferating macroalga Asparagopsis taxiformis and the coral Astroides calycularis induces changes in microbiome and metabolomic fingerprints. Sci Rep. 2017 02 20;7:42625 Authors: Greff S, Aires T, Serrão EA, Engelen AH, Thomas OP, Pérez T Abstract Mediterranean Sea ecosystems are considered as hotspots of biological introductions, exposed to possible negative effects of non-indigenous species. In such temperate marine ecosystems, macroalgae may be dominant, with a great percentage of their diversity represented by introduced species. Their interaction with temperate indigenous benthic organisms have been poorly investigated. To provide new insights, we performed an experimental study on the interaction between the introduced proliferative red alga Asparagopsis taxiformis and the indigenous Mediterranean coral Astroides calycularis. The biological response measurements included meta-barcoding of the associated microbial communities and metabolomic fingerprinting of both species. Significant changes were detected among both associated microbial communities, the interspecific differences decreasing with stronger host interaction. No short term effects of the macroalga on the coral health, neither on its polyp activity or its metabolism, were detected. In contrast, the contact interaction with the coral induced a change in the macroalgal metabolomic fingerprint with a significant increase of its bioactivity against the marine bacteria Aliivibrio fischeri. This induction was related to the expression of bioactive metabolites located on the macroalgal surface, a phenomenon which might represent an immediate defensive response of the macroalga or an allelopathic offense against coral. PMID: 28218290 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Wed, 31/10/2018 - 14:34
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 2018/10/31PubMed 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

Wed, 31/10/2018 - 11:31
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 2018/10/31PubMed 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.

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