PubMed

Related Articles Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model. Chin Med J (Engl). 2016 20th Mar;129(6):702-708 Authors: Zou LH, Liu JP, Zhang H, Wu SB, Ji BY Abstract BACKGROUND: Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. METHODS: To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without ( DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups. RESULTS: Metabolic profiling of brain was distinctive significantly between the two groups (Q 2 Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D. CONCLUSIONS: The present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone. PMID: 26960374 [PubMed - as supplied by publisher]

Related Articles [Anti-dementia effect of Tongluo Xingnao effervescent tablet based on urinary metabonomics]. Zhongguo Zhong Yao Za Zhi. 2015 Aug;40(16):3287-92 Authors: Wei JP, Zhang YJ, Ma YT, Xu SJ, Wang YY Abstract Tongluo Xingnao effervescent tablet (TLXNET) is a patented prescription, which comes from modified Xionggui decoction and can improve cognitive function. However, its effect on the urine metabolites and anti-dementia mechanism in the dementia model rats induced by hippocampal injection with Aβ25-35 remains unclear. The experiment focused on the changes in trajectory and inter-relationship among the urinary metabolite of rats in the blank group, Aβ25-35 hippocampal injection dementia model group and the TLXNET intervention group, in order to determine theirs characteristic metabolic markers and explain the anti-dementia effect of TLX-NET base on the change of metabolic trajectory of these bio-markers. According to the experimental results, 5, 6-indolequinone, 4-hydroxyphenyl pyruvic acid (4-HPPA), cortisol and 3-thiosulfate lactic were preliminarily identified as the characteristic metabolic markers. They mainly participate in dopamine system, glucocorticoids and energy metabolic pathways. TLXNET can apparently downregulate the disturbances of metabolic trajectory of the four bio-markers. The experiment indicates that the dementia model induced by injecting Aβ25-3 into hippocampus has its characteristic endogenous metabolic markers in urine, and ELXNET can ameliorate dementia by down-regulating the disturbances of metabolic trajectory. PMID: 26790309 [PubMed - indexed for MEDLINE]

Related Articles Study of levan productivity from Bacillus subtilis Natto by surface response methodology and its antitumor activity against HepG2 cells using metabolomic approach. Pak J Pharm Sci. 2015 Nov;28(6):1917-26 Authors: Cabral de Melo FC, Borsato D, de Macedo Júnior FC, Mantovani MS, Luiz RC, Colabone-Celligoi MA Abstract Levan productivity of Bacillus subtilis Natto was evaluated in submerged culture varying the pH, temperature and culture time, using factorial design and response surface methodology. The characterization of levan molecular weight was performed by HPSEC and its antitumor activity against HepG2 cells using metabolomic approach was also evaluated. At first, the variables investigated, as well as their interactions, demonstrated significant effect. Further, a second design using the same variables at different levels was developed. Thus, according to the model, an optimized value corresponding to 5.82 g.L⁻¹.h⁻¹ was achieved at pH 8, 39.5°C in 21 hours, the highest value reported so far. After analysis by HPSEC, two molecular weights were obtained corresponding to 72.37 and 4146 kDa. The levan promoted an increase of acetate, alanine, lactate and phosphocreatine in HepG2 cells suggesting an alteration in the bioenergetics pathways and cellular homeostasis by intracellular accumulation of lactate, justifying its antitumor activity. PMID: 26639487 [PubMed - indexed for MEDLINE]

Related Articles LKB1 couples glucose metabolism to insulin secretion in mice. Diabetologia. 2015 Jul;58(7):1513-22 Authors: Fu A, Robitaille K, Faubert B, Reeks C, Dai XQ, Hardy AB, Sankar KS, Ogrel S, Al-Dirbashi OY, Rocheleau JV, Wheeler MB, MacDonald PE, Jones R, Screaton RA Abstract AIMS/HYPOTHESIS: Precise regulation of insulin secretion by the pancreatic beta cell is essential for the maintenance of glucose homeostasis. Insulin secretory activity is initiated by the stepwise breakdown of ambient glucose to increase cellular ATP via glycolysis and mitochondrial respiration. Knockout of Lkb1, the gene encoding liver kinase B1 (LKB1) from the beta cell in mice enhances insulin secretory activity by an undefined mechanism. Here, we sought to determine the molecular basis for how deletion of Lkb1 promotes insulin secretion. METHODS: To explore the role of LKB1 on individual steps in the insulin secretion pathway, we used mitochondrial functional analyses, electrophysiology and metabolic tracing coupled with by gas chromatography and mass spectrometry. RESULTS: Beta cells lacking LKB1 surprisingly display impaired mitochondrial metabolism and lower ATP levels following glucose stimulation, yet compensate for this by upregulating both uptake and synthesis of glutamine, leading to increased production of citrate. Furthermore, under low glucose conditions, Lkb1(-/-) beta cells fail to inhibit acetyl-CoA carboxylase 1 (ACC1), the rate-limiting enzyme in lipid synthesis, and consequently accumulate NEFA and display increased membrane excitability. CONCLUSIONS/INTERPRETATION: Taken together, our data show that LKB1 plays a critical role in coupling glucose metabolism to insulin secretion, and factors in addition to ATP act as coupling intermediates between feeding cues and secretion. Our data suggest that beta cells lacking LKB1 could be used as a system to identify additional molecular events that connect metabolism to cellular excitation in the insulin secretion pathway. PMID: 25874445 [PubMed - indexed for MEDLINE]

Related Articles Metabolomic profiling in the prediction of gestational diabetes mellitus. Diabetologia. 2015 Jun;58(6):1329-32 Authors: Bentley-Lewis R, Huynh J, Xiong G, Lee H, Wenger J, Clish C, Nathan D, Thadhani R, Gerszten R Abstract AIMS/HYPOTHESIS: Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM. METHODS: We conducted a nested case-control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n = 96) were matched to women with NGT (n = 96) by age, BMI, gravidity and parity. Liquid chromatography-mass spectrometry was used to measure the levels of 91 metabolites. RESULTS: Data analyses revealed the following characteristics (mean ± SD): age 32.8 ± 4.4 years, BMI 28.3 ± 5.6 kg/m(2), gravidity 2 ± 1 and parity 1 ± 1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p < 0.05). The levels of the BCAAs did not differ significantly between GDM and NGT. CONCLUSIONS/INTERPRETATION: Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary. PMID: 25748329 [PubMed - indexed for MEDLINE]

17 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 2016/03/10PubMed comprises more than 24 million 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.

22 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 2016/03/08PubMed comprises more than 24 million 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.

Optimization of a liquid chromatography ion mobility-mass spectrometry method for untargeted metabolomics using experimental design and multivariate data analysis. Anal Chim Acta. 2016 Mar 24;913:55-62 Authors: Tebani A, Schmitz-Afonso I, Rutledge DN, Gonzalez BJ, Bekri S, Afonso C Abstract High-resolution mass spectrometry coupled with pattern recognition techniques is an established tool to perform comprehensive metabolite profiling of biological datasets. This paves the way for new, powerful and innovative diagnostic approaches in the post-genomic era and molecular medicine. However, interpreting untargeted metabolomic data requires robust, reproducible and reliable analytical methods to translate results into biologically relevant and actionable knowledge. The analyses of biological samples were developed based on ultra-high performance liquid chromatography (UHPLC) coupled to ion mobility - mass spectrometry (IM-MS). A strategy for optimizing the analytical conditions for untargeted UHPLC-IM-MS methods is proposed using an experimental design approach. Optimization experiments were conducted through a screening process designed to identify the factors that have significant effects on the selected responses (total number of peaks and number of reliable peaks). For this purpose, full and fractional factorial designs were used while partial least squares regression was used for experimental design modeling and optimization of parameter values. The total number of peaks yielded the best predictive model and is used for optimization of parameters setting. PMID: 26944989 [PubMed - in process]

Comprehensive tissue-specific proteome analysis of drought stress responses in Pennisetum glaucum (L.) R. Br. (Pearl millet). J Proteomics. 2016 Mar 1; Authors: Ghatak A, Chaturvedi P, Nagler M, Roustan V, Lyon D, Bachmann G, Postl W, Schröfl A, Desai N, Varshney RK, Weckwerth W Abstract Pearl millet is the fifth most important cereal crop worldwide and cultivated especially by small holder farmers in arid and semi-arid regions because of its drought and salt tolerance. The molecular mechanisms of drought stress tolerance in Pennisetum remain elusive. We have used a shotgun proteomics approach to investigate protein signatures from different tissues under drought and control conditions. Drought stressed plants showed significant changes in stomatal conductance and increased root growth compared to the control plants. Root, leaf and seed tissues were harvested and 2281 proteins were identified and quantified in total. Leaf tissue showed the largest number of significant changes (120), followed by roots (25) and seeds (10). Increased levels of root proteins involved in cell wall-, lipid-, secondary- and signaling metabolism and the concomitantly observed increased root length point to an impaired shoot-root communication under drought stress. The harvest index (HI) showed a significant reduction under drought stress. Proteins with a high correlation to the HI were identified using sparse partial least square (sPLS) analysis. Considering the importance of Pearl millet as a stress tolerant food crop, this study provides a first reference data set for future investigations of the underlying molecular mechanisms. BIOLOGICAL SIGNIFICANCE: Drought stress is the most limiting factor for plant growth and crop production worldwide. At the same time drought susceptible cereal crops are among the largest producers worldwide. In contrast, Pearl millet is a drought and salt tolerant cereal crop especially used in arid and semi-arid regions by small farmers. The multifactorial molecular mechanisms of this unique drought tolerance are not known. Here, we employ shotgun proteomics for a first characterization of the Pearl millet drought stress proteome. The experimental setup and the data set generated from this study reveal comprehensive physiological and proteomic responses of the drought stressed Pearl millet plants. Our study reveals statistically significant tissue-specific protein signatures during the adaptation to drought conditions. Thus, the work provides a first reference study of the drought stress proteome and related drought responsive proteins (DRP's) in Pearl millet. PMID: 26944736 [PubMed - as supplied by publisher]

Integrating transcriptomics and metabolomics to characterise the response of Astragalus membranaceus Bge. var. mongolicus (Bge.) to progressive drought stress. BMC Genomics. 2016;17(1):188 Authors: Jia X, Sun C, Zuo Y, Li G, Li G, Ren L, Chen G Abstract BACKGROUND: Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao (A. mongolicus) is an important traditional Chinese herb that is cultivated on a large scale in northwestern China. Understanding plant responses to drought has important effects on ecological environment recovery and local economic development. Here, we combined transcriptomics (Illumina Hiseq 2000) and metabolomics ((1)H-NMR) to investigate how the roots of two-year-old A. mongolicus responded to 14 days of progressive drought stress. RESULTS: The dried soil reduced the relative water content (RWC) of the leaves and biomass, induced the differential expression of a large fraction of the transcriptome and significantly altered the metabolic processes. PCA analysis demonstrated that the sucrose, proline, and malate metabolites contributed greatly to the separation. Strikingly, proline was increased by almost 60-fold under severe stress compared to the control. Some backbone pathways, including glycolysis, tricarboxylic acid (TCA) cycle, glutamate-mediated proline biosynthesis, aspartate family metabolism and starch and sucrose metabolism, were significantly affected by drought. An integrated analysis of the interaction between key genes and the altered metabolites involved in these pathways was performed. CONCLUSIONS: Our findings demonstrated that the expression of drought-responsive genes showed a strong stress-dose dependency. Analysis of backbone pathways of the transcriptome and metabolome revealed specific genotypic responses to different levels of drought. The variation in molecular strategies to the drought may play an important role in how A. mongolicus and other legume crops adapt to drought stress. PMID: 26944555 [PubMed - as supplied by publisher]

43 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 2016/03/05PubMed comprises more than 24 million 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.

23 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 2016/03/02PubMed comprises more than 24 million 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.

Oxidative stress in northern elephant seals: Integration of omics approaches with ecological and experimental studies. Comp Biochem Physiol A Mol Integr Physiol. 2016 Feb 25; Authors: Crocker DE, Khudyakov JI, Champagne CD Abstract Northern elephant seals experience conditions that increase oxidative stress (OS), including extended fasting, ischemia and hypoxia during breath-holds, and immune responses during colonial breeding. Increased OS is suggested by increases in tissue and plasma concentrations of pro-oxidant enzymes NADPH oxidase and xanthine oxidase (XO). Serum cortisol concentrations were positively associated with XO concentrations and damage markers. Elephant seals exhibit robust anti-oxidant responses as evidenced by increases in anti-oxidant enzymes in plasma and tissues. These responses were sufficient to prevent oxidative damage during breath-holds and extended fasts in juveniles. However, high rates of energy expenditure during breeding were associated with increased evidence for oxidative damage to lipids, proteins and DNA in adults. We integrated investigations of the fasting metabolome and muscle and blubber transcriptomes into our oxidative stress studies. Non-targeted metabolomics analysis of fasting seals identified 227 known metabolites in plasma, including those related to glutathione and purine metabolism. Changes in plasma metabolites suggested that glutathione biosynthesis increased during fasting in weaned pups but not in lactating females. We produced the first reference sequence for elephant seals by RNA sequencing of skeletal muscle and adipose tissue transcriptomes and de novo transcriptome assembly. We annotated muscle and adipose transcripts and identified thousands of genes, including potential mediators of OS. This resource provides elephant seal-specific gene sequences, complements existing metabolite and protein expression studies and provides tools for examining cellular responses to OS in a variety of contexts. We examined changes in tissue gene expression in response to experimental elevation of plasma cortisol. Responses included downregulation of Negative Regulator of Reactive Oxygen Species (NRROS) in muscle, a regulator that limits reactive oxygen species production by tissues. These tools provide novel views of the cellular and systemic mechanisms that enable seals to tolerate high levels of OS. PMID: 26924792 [PubMed - as supplied by publisher]

Acute phase inflammation is characterized by rapid changes in plasma/peritoneal fluid N-glycosylation in mice. Glycoconj J. 2016 Feb 29; Authors: Rombouts Y, Jónasdóttir HS, Hipgrave Ederveen AL, Reiding KR, Jansen BC, Freysdottir J, Hardardottir I, Ioan-Facsinay A, Giera M, Wuhrer M Abstract Murine zymosan-induced peritonitis is a widely used model for studying the molecular and cellular events responsible for the initiation, persistence and/or resolution of inflammation. Among these events, it is becoming increasingly evident that changes in glycosylation of proteins, especially in the plasma and at the site of inflammation, play an important role in the inflammatory response. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS)-based glycosylation profiling, we investigated the qualitative and quantitative effect of zymosan-induced peritonitis on N-glycosylation in mouse plasma and peritoneal fluid. Our results show that both N-glycomes exhibit highly similar glycosylation patterns, consisting mainly of diantennary and triantennary complex type N-glycans with high levels (>95 %) of galactosylation and sialylation (mostly NeuGc) and a medium degree of core fucosylation (30 %). Moreover, MS/MS structural analysis, assisted by linkage-specific derivatization of sialic acids, revealed the presence of O-acetylated sialic acids as well as disialylated antennae ("branching sialylation") characterized by the presence of α2-6-linked NeuGc on the GlcNAc of the NeuGcα2-3-Galβ1-3-GlcNAc terminal motif. A significant decrease of (core) fucosylation together with an increase of both α2-3-linked NeuGc and "branching sialylation" were observed in N-glycomes of mice challenged with zymosan, but not in control mice injected with PBS. Importantly, substantial changes in glycosylation were already observed 12 h after induction of peritonitis, thereby demonstrating an unexpected velocity of the biological mechanisms involved. PMID: 26924641 [PubMed - as supplied by publisher]

Global metabolic analyses identify key differences in metabolite levels between polymyxin-susceptible and polymyxin-resistant Acinetobacter baumannii. Sci Rep. 2016;6:22287 Authors: Mahamad Maifiah MH, Cheah SE, Johnson MD, Han ML, Boyce JD, Thamlikitkul V, Forrest A, Kaye KS, Hertzog P, Purcell AW, Song J, Velkov T, Creek DJ, Li J Abstract Multidrug-resistant Acinetobacter baumannii presents a global medical crisis and polymyxins are used as the last-line therapy. This study aimed to identify metabolic differences between polymyxin-susceptible and polymyxin-resistant A. baumannii using untargeted metabolomics. The metabolome of each A. baumannii strain was measured using liquid chromatography-mass spectrometry. Multivariate and univariate statistics and pathway analyses were employed to elucidate metabolic differences between the polymyxin-susceptible and -resistant A. baumannii strains. Significant differences were identified between the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii strains. The lipopolysaccharide (LPS) deficient, polymyxin-resistant 19606R showed perturbation in specific amino acid and carbohydrate metabolites, particularly pentose phosphate pathway (PPP) and tricarboxylic acid (TCA) cycle intermediates. Levels of nucleotides were lower in the LPS-deficient 19606R. Furthermore, 19606R exhibited a shift in its glycerophospholipid profile towards increased abundance of short-chain lipids compared to the parent polymyxin-susceptible ATCC 19606. In contrast, in a pair of clinical isolates 03-149.1 (polymyxin-susceptible) and 03-149.2 (polymyxin-resistant, due to modification of lipid A), minor metabolic differences were identified. Notably, peptidoglycan biosynthesis metabolites were significantly depleted in both of the aforementioned polymyxin-resistant strains. This is the first comparative untargeted metabolomics study to show substantial differences in the metabolic profiles of the polymyxin-susceptible and -resistant A. baumannii. PMID: 26924392 [PubMed - as supplied by publisher]

Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine. J Pharm Biomed Anal. 2016 Feb 15;123:179-185 Authors: Li A, Guo X, Xie J, Liu X, Zhang Z, Li Y, Zhang Y Abstract Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2mmol/L, 0.4mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis. A "supervised" Support Vector Machine (SVM) study was used to optimize and verify the reliability of these biomarkers. In these biomarkers, all biomarkers, including carnitine, acetylcarnitine, lysoPC(16:0), proline, glutamic acid, pyroglutamic acid, leucine, pantothenic acid, tryptophan, indoleacrylic acid and citric acid, revealed a downward trend with the increase of dosage. Moreover, pathway analysis showed that these metabolites were associated with amino acid metabolism, energy metabolism and sphingolipid metabolism, which contributes to a further understanding of the toxicity mechanism of Corex Periplocae and its clinical safety. Additionally, we demonstrate that an UPLC-Q-TOF/MS-based metabolomic approach is a powerful tool and provides a promising approach for assessing the toxicity of traditional Chinese medicine and drug safety screening. PMID: 26924293 [PubMed - as supplied by publisher]

Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism. Cell Metab. 2016 Feb 23; Authors: Nikkanen J, Forsström S, Euro L, Paetau I, Kohnz RA, Wang L, Chilov D, Viinamäki J, Roivainen A, Marjamäki P, Liljenbäck H, Ahola S, Buzkova J, Terzioglu M, Khan NA, Pirnes-Karhu S, Paetau A, Lönnqvist T, Sajantila A, Isohanni P, Tyynismaa H, Nomura DK, Battersby BJ, Velagapudi V, Carroll CJ, Suomalainen A Abstract Mitochondrial dysfunction affects cellular energy metabolism, but less is known about the consequences for cytoplasmic biosynthetic reactions. We report that mtDNA replication disorders caused by TWINKLE mutations-mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)-remodel cellular dNTP pools in mice. MM muscle shows tissue-specific induction of the mitochondrial folate cycle, purine metabolism, and imbalanced and increased dNTP pools, consistent with progressive mtDNA mutagenesis. IOSCA-TWINKLE is predicted to hydrolyze dNTPs, consistent with low dNTP pools and mtDNA depletion in the disease. MM muscle also modifies the cytoplasmic one-carbon cycle, transsulfuration, and methylation, as well as increases glucose uptake and its utilization for de novo serine and glutathione biosynthesis. Our evidence indicates that the mitochondrial replication machinery communicates with cytoplasmic dNTP pools and that upregulation of glutathione synthesis through glucose-driven de novo serine biosynthesis contributes to the metabolic stress response. These results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy. PMID: 26924217 [PubMed - as supplied by publisher]

Cognitive Impairment by Antibiotic-Induced Gut Dysbiosis: Analysis of Gut Microbiota-Brain Communication. Brain Behav Immun. 2016 Feb 23; Authors: Fröhlich EE, Farzi A, Mayerhofer R, Reichmann F, Jačan A, Wagner B, Zinser E, Bordag N, Magnes C, Fröhlich E, Kashofer K, Gorkiewicz G, Holzer P Abstract Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-D-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis. PMID: 26923630 [PubMed - as supplied by publisher]

Gut Microbiome of Coexisting BaAka Pygmies and Bantu Reflects Gradients of Traditional Subsistence Patterns. Cell Rep. 2016 Feb 24; Authors: Gomez A, Petrzelkova KJ, Burns MB, Yeoman CJ, Amato KR, Vlckova K, Modry D, Todd A, Jost Robinson CA, Remis MJ, Torralba MG, Morton E, Umaña JD, Carbonero F, Gaskins HR, Nelson KE, Wilson BA, Stumpf RM, White BA, Leigh SR, Blekhman R Abstract To understand how the gut microbiome is impacted by human adaptation to varying environments, we explored gut bacterial communities in the BaAka rainforest hunter-gatherers and their agriculturalist Bantu neighbors in the Central African Republic. Although the microbiome of both groups is compositionally similar, hunter-gatherers harbor increased abundance of Prevotellaceae, Treponema, and Clostridiaceae, while the Bantu gut microbiome is dominated by Firmicutes. Comparisons with US Americans reveal microbiome differences between Africans and westerners but show western-like features in the Bantu, including an increased abundance of predictive carbohydrate and xenobiotic metabolic pathways. In contrast, the hunter-gatherer gut shows increased abundance of predicted virulence, amino acid, and vitamin metabolism functions, as well as dominance of lipid and amino-acid-derived metabolites, as determined through metabolomics. Our results demonstrate gradients of traditional subsistence patterns in two neighboring African groups and highlight the adaptability of the microbiome in response to host ecology. PMID: 26923597 [PubMed - as supplied by publisher]

Effects of Pinellia ternata (Thunb.) Berit. on the metabolomic profiles of placenta and amniotic fluid in pregnant rats. J Ethnopharmacol. 2016 Feb 23; Authors: Xie HH, Xu JY, Xie T, Meng X, Lin LL, He LL, Wu H, Shan JJ, Wang SC Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Banxia (BX) is the root of Pinellia ternata (Thunb.) Berit. Its processed products, such as Jiang Banxia (JBX), have been clinically used in traditional Chinese medicine to treat vomiting, coughing, and inflammation. However, data for their safety for pregnant women are contradictory and confusing. AIM OF THE STUDY: To further explore the safety of BX, an ultra-performance liquid chromatography coupled with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) metabolomics approach was used to evaluate the metabolic perturbation in pregnant rats caused by BX and JBX. MATERIALS AND METHODS: Placenta and amniotic fluid samples were collected from control Sprague-Dawley pregnant rats and exposed to BX suspension and JBX decoction (1.434g/kg/day). Samples were analyzed using LC-MS and GC-MS. The acquired MS data of above samples were further subjected to multivariate data analysis, and the significantly altered metabolites were identified. The associated pathways were constructed using MetaboAnalyst 3.0. RESULTS: The weight and histopathology of the placenta from each group of rats had no definite difference. However, we found 20 differential endogenous metabolites that changed significantly in the placenta and amniotic fluid samples. The alterations of identified metabolites indicated a perturbation in glycerophospholipid metabolism, amino acid metabolism, and carbohydrate metabolism in pregnant rats exposed to BX and JBX. CONCLUSION: In summary, this work suggested that oral administration of BX and JBX may induce disturbances in the intermediary metabolism in pregnant rats. This work contributes to further understanding the safety of BX and its processed products. PMID: 26923539 [PubMed - as supplied by publisher]