PubMed

Trans-Fats Inhibit Autophagy Induced by Saturated Fatty Acids. EBioMedicine. 2018 Mar 27;: Authors: Sauvat A, Chen G, Müller K, Tong M, Aprahamian F, Durand S, Cerrato G, Bezu L, Leduc M, Franz J, Rockenfeller P, Sadoshima J, Madeo F, Kepp O, Kroemer G Abstract Depending on the length of their carbon backbone and their saturation status, natural fatty acids have rather distinct biological effects. Thus, longevity of model organisms is increased by extra supply of the most abundant natural cis-unsaturated fatty acid, oleic acid, but not by that of the most abundant saturated fatty acid, palmitic acid. Here, we systematically compared the capacity of different saturated, cis-unsaturated and alien (industrial or ruminant) trans-unsaturated fatty acids to provoke cellular stress in vitro, on cultured human cells expressing a battery of distinct biosensors that detect signs of autophagy, Golgi stress and the unfolded protein response. In contrast to cis-unsaturated fatty acids, trans-unsaturated fatty acids failed to stimulate signs of autophagy including the formation of GFP-LC3B-positive puncta, production of phosphatidylinositol-3-phosphate, and activation of the transcription factor TFEB. When combined effects were assessed, several trans-unsaturated fatty acids including elaidic acid (the trans-isomer of oleate), linoelaidic acid, trans-vaccenic acid and palmitelaidic acid, were highly efficient in suppressing autophagy and endoplasmic reticulum stress induced by palmitic, but not by oleic acid. Elaidic acid also inhibited autophagy induction by palmitic acid in vivo, in mouse livers and hearts. We conclude that the well-established, though mechanistically enigmatic toxicity of trans-unsaturated fatty acids may reside in their capacity to abolish cytoprotective stress responses induced by saturated fatty acids. PMID: 29606629 [PubMed - as supplied by publisher]

Application of sequential and orthogonalised-partial least squares (SO-PLS) regression to predict sensory properties of Cabernet Sauvignon wines from grape chemical composition. Food Chem. 2018 Aug 01;256:195-202 Authors: Niimi J, Tomic O, Næs T, Jeffery DW, Bastian SEP, Boss PK Abstract The current study determined the applicability of sequential and orthogonalised-partial least squares (SO-PLS) regression to relate Cabernet Sauvignon grape chemical composition to the sensory perception of the corresponding wines. Grape samples (n = 25) were harvested at a similar maturity and vinified identically in 2013. Twelve measures using various (bio)chemical methods were made on grapes. Wines were evaluated using descriptive analysis with a trained panel (n = 10) for sensory profiling. Data was analysed globally using SO-PLS for the entire sensory profiles (SO-PLS2), as well as for single sensory attributes (SO-PLS1). SO-PLS1 models were superior in validated explained variances than SO-PLS2. SO-PLS provided a structured approach in the selection of predictor chemical data sets that best contributed to the correlation of important sensory attributes. This new approach presents great potential for application in other explorative metabolomics studies of food and beverages to address factors such as quality and regional influences. PMID: 29606438 [PubMed - in process]

Related Articles Chemical profiling of two congeneric sea mat corals along the Brazilian coast: adaptive and functional patterns. Chem Commun (Camb). 2018 Feb 20;54(16):1952-1955 Authors: Costa-Lotufo LV, Carnevale-Neto F, Trindade-Silva AE, Silva RR, Silva GGZ, Wilke DV, Pinto FCL, Sahm BDB, Jimenez PC, Mendonça JN, Lotufo TMC, Pessoa ODL, Lopes NP Abstract Metabolomic profiles were explored to understand environmental and taxonomic influences on the metabolism of two congeneric zoanthids, Palythoa caribaeorum and P. variabilis, collected across distinct geographical ranges. Integrated mass spectrometry data suggested the major influence of geographical location on chemical divergence when compared to species differentiation. PMID: 29323379 [PubMed - indexed for MEDLINE]

Related Articles Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention. Cancer Metastasis Rev. 2017 Jun;36(2):289-303 Authors: Ornelas A, Zacharias-Millward N, Menter DG, Davis JS, Lichtenberger L, Hawke D, Hawk E, Vilar E, Bhattacharya P, Millward S Abstract After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism. PMID: 28762014 [PubMed - indexed for MEDLINE]

Regulation of Kynurenine Metabolism by a Ketogenic Diet. J Lipid Res. 2018 Mar 31;: Authors: Heischmann S, Gano LB, Quinn K, Liang LP, Klepacki J, Christians U, Reisdorph N, Patel M Abstract Ketogenic diets (KDs) are increasingly utilized as treatments for epilepsy, other neurological diseases, and cancer. Despite their long history in suppressing seizures, the distinct molecular mechanisms of action of KDs are still largely unknown. The goal of this study was to identify key metabolites and pathways altered in hippocampus and plasma of rats fed a KD vs. control diet either ad libitum or calorically restricted to 90% of the recommended intake. This was accomplished using a combination of targeted methods and untargeted mass spectrometry-based metabolomics analyses. Various metabolites of and related to the tryptophan degradation pathway, such as kynurenine and kynurenic acid, as well as enzyme cofactors showed significant changes between groups fed different diets and/or calorie amounts in plasma and/or the hippocampus. Kynurenine was significantly downregulated in both matrices in animals of the control diet-calorically restricted, KD-ad libitum, and KD-calorically restricted groups compared to the control diet-ad libitum group. Our data suggest that the tryptophan degradation pathway is a key target of the KD. PMID: 29605816 [PubMed - as supplied by publisher]

Baseline levels of metabolites in different tissues of mussel Mytilus galloprovincialis (Bivalvia: Mytilidae). Comp Biochem Physiol Part D Genomics Proteomics. 2018 Mar 27;26:32-39 Authors: Cappello T, Giannetto A, Parrino V, Maisano M, Oliva S, De Marco G, Guerriero G, Mauceri A, Fasulo S Abstract The Mediterranean mussel Mytilus galloprovincialis (Lamarck 1819) is a popular shellfish commonly included in human diet and is routinely used as bioindicator in environmental monitoring programmes worldwide. Recently, metabolomics has emerged as a powerful tool both in food research and ecotoxicology for monitoring mussels' freshness and assessing the effects of environmental changes. However, there is still a paucity of data on complete metabolic baseline of mussel tissues. To mitigate this knowledge gap, similarities and differences in metabolite profile of digestive gland (DG), gills (G), and posterior adductor muscle (PAM) of aquaculture-farmed M. galloprovincialis were herein investigated by a proton nuclear magnetic resonance (1H NMR)-based metabolomic approach and discussed considering their physiological role. A total of 44 metabolites were identified in mussel tissues and grouped in amino acids, energy metabolites, osmolytes, neurotransmitters, nucleotides, alkaloids, and miscellaneous metabolites. A PCA showed that mussel tissues clustered separately from each other, suggesting a clear differentiation in their metabolic profiles. A Venn diagram revealed that mussel DG, G and PAM shared 27 (61.36%) common metabolites, though with different concentrations. Osmolytes were found to dominate the metabolome of all tissues. The DG exhibited higher level of glutathione and carbohydrates. The G showed greater level of osmolytes and the exclusive presence of neurotransmitters, namely acetylcholine and serotonin. In PAM higher levels of energetics-related metabolites were found. Overall, findings from this study are helpful for a better understanding of mussel tissue-specific physiological functions as well as for future NMR-based metabolomic investigations of marine mussel health and safety. PMID: 29605489 [PubMed - as supplied by publisher]

Related Articles Identification of metabolites in plasma for predicting survival in glioblastoma. Mol Carcinog. 2018 Mar 30;: Authors: Shen J, Song R, Hodges TR, Heimberger AB, Zhao H Abstract Circulating metabolomics profiling holds prognostic potential. However, such efforts have not been extensively carried out in glioblastoma. In this study, two-step (training and testing) metabolomics profiling was conducted from the plasma samples of 159 glioblastoma patients. Metabolomics profiling was tested for correlation with 2-year overall and disease-free survivals. Arginine, methionine, and kynurenate levels were significantly associated with 2-year overall survival in both the training and testing sets. In the combined sets, elevated levels of arginine and methionine were associated with a 34% and 37% increased probability whereas kynurenate was associated with a 55% decreased probability of 2-year overall survival. These three metabolites were also significantly associated with 2-year disease-free survival. Risk scores were generated using the linear combination of levels of these significant metabolites. Glioblastoma patients with a high-risk score exhibited a 2.41-fold decreased probability of 2-year overall survival (hazard ratio (HR) = 2.41; 95% Confidence Interval (CI) = 1.20-4.93) and a 3.17 fold decreased probability of 2-year disease free survival (HR = 3.17, 95% CI = 1.42-7.54) relative to those with a low-risk score. In conclusion, we identified a unique plasma metabolite profile that is predictive of glioblastoma prognosis. This article is protected by copyright. All rights reserved. PMID: 29603794 [PubMed - as supplied by publisher]

Related Articles Changes in Plasma Metabolite Concentrations after a Low-Glycemic Index Diet Intervention. Mol Nutr Food Res. 2018 Mar 30;:e1700975 Authors: Hernández-Alonso P, Giardina S, Cañueto D, Salas-Salvadó J, Cañellas N, Bulló M Abstract SCOPE: To examine whether a low-glycemic index (LGI) diet improves a set of plasma metabolites related to different metabolic diseases and compared to a high-glycemic index (HGI) diet and a low-fat (LF) diet. METHODS AND RESULTS: We conducted a parallel, randomized trial with three intervention diets: a LGI diet, a HGI diet and a LF diet. A total of 122 adult overweight and obese subjects were enrolled in the study for 6 months. Blood samples were collected at baseline and at the end of the intervention. We analyzed the plasma metabolomic profile of 102 subjects using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF and NMR. Both univariate and multivariate analysis were performed. Serine levels were significantly higher following the LGI diet compared to both the HGI and LF diets (q = 0.002), whereas leucine (q = 0.015) and valine (q = 0.024) were lower in the LGI diet compared to the LF diet. A set of two sphingomyelins, two lysophosphatidylcholines and six phosphatidylcholines were significantly modulated after the LGI diet compared to the HGI and LF diets (q<0.05). We found significant correlations between changes in plasma amino acids and lipid species with changes in body weight, glucose, insulin and some inflammatory markers. CONCLUSION: Our results suggest that a LGI diet modulates certain circulating amino acids and lipid levels. These findings may explain the health benefits attributed to LGI diets in metabolic diseases such as type 2 diabetes. This article is protected by copyright. All rights reserved. PMID: 29603657 [PubMed - as supplied by publisher]

Related Articles Hepatic Abundance and Activity of Androgen and Drug Metabolizing Enzyme, UGT2B17, are Associated with Genotype, Age, and Sex. Drug Metab Dispos. 2018 Mar 30;: Authors: Bhatt DK, Basit A, Zhang H, Gaedigk A, Lee SB, Claw KG, Mehrotra A, Chaudhry AS, Pearce RE, Gaedigk R, Broeckel U, Thornton TA, Nickerson DA, Schuetz EG, Amory J, Leeder JS, Prasad B Abstract The major objective of this study was to investigate association of genetic and non-genetic factors with variability in protein abundance and in vitro activity of the androgen metabolizing enzyme, UGT2B17, in human liver microsomes (n=455). UGT2B17 abundance was quantified by LC-MS/MS proteomics and enzyme activity was determined by using testosterone and dihydrotestosterone as in vitro probe substrates. Genotyping or gene resequencing and mRNA expression were also evaluated. Multivariate analysis was used to test association of UGT2B17 copy number variation, single nucleotide polymorphisms (SNPs), age and sex with its mRNA expression, abundance and activity. UGT2B17 gene copy number and SNPs (rs7436962, rs9996186, rs28374627 and rs4860305) were associated with gene expression, protein levels and androgen glucuronidation rates in a gene-dose dependent manner. UGT2B17 protein (mean ± SD pmol per mg microsomal protein) is sparsely expressed in children below 9 years (0.12 ± 0.24), but profoundly increases from age 9 years to adults (~10 fold) with ~2.6-fold higher abundance in males than females (1.2 vs. 0.47). Association of androgen glucuronidation with UGT2B15 abundance was only observed in the low UGT2B17 expressers. These data can be used to predict variability in the metabolism of UGT2B17 substrates. Drug companies should include UGT2B17 in early phenotyping assays during drug discovery to avoid late clinical failures. PMID: 29602798 [PubMed - as supplied by publisher]

Related Articles Metabolomics and Metabolic Reprogramming in Kidney Cancer. Semin Nephrol. 2018 Mar;38(2):175-182 Authors: Weiss RH Abstract Kidney cancer, or renal cell carcinoma (RCC), is a disease of increasing incidence that commonly is seen in the general practice of nephrology. Despite this state of affairs, this fascinating and highly morbid disease frequently is under-represented, or even absent, from the curriculum of nephrologists in training and generally is underemphasized in national nephrology meetings, both scientific as well as clinical. Although classic concepts in cancer research in general had led to the concept that cancer is a disease resulting from mutations in the control of growth-regulating pathways, reinforced by the discovery of oncogenes, more contemporary research, particularly in kidney cancer, has uncovered changes in metabolic pathways mediated by those same genes that control tumor energetics and biosynthesis. This adaptation of classic biochemical pathways to the tumor's advantage has been labeled metabolic reprogramming. For example, in the case of kidney cancer there exists a near-universal presence of von Hippel-Lindau tumor suppressor (pVHL) inactivation in the most common form, clear cell RCC (ccRCC), leading to activation of hypoxia-relevant and other metabolic pathways. Studies of this and other pathways in clear cell RCC (ccRCC) have been particularly revealing, leading to the concept that ccRCC can itself be considered a metabolic disease. For this reason, the relatively new method of metabolomics has become a useful technique in the study of ccRCC to tease out those pathways that have been reprogrammed by the tumor to its maximum survival advantage. Furthermore, identification of the nodes of such pathways can lead to novel areas for drug intervention in a disease for which such targets are seriously lacking. Further research and dissemination of these concepts, likely using omics techniques, will lead to clinical trials of therapeutics specifically targeted to tumor metabolism, rather than those generally toxic to all proliferating cells. Such novel agents are highly likely to be more effective than existing drugs and to have far fewer adverse effects. This review provides a general overview of the technique of metabolomics and then discusses how it and other omics techniques have been used to further our understanding of the basic biology of kidney cancer as well as to identify new therapeutic approaches. PMID: 29602399 [PubMed - in process]

Related Articles Genome-Wide Association Studies of Metabolite Concentrations (mGWAS): Relevance for Nephrology. Semin Nephrol. 2018 Mar;38(2):151-174 Authors: Köttgen A, Raffler J, Sekula P, Kastenmüller G Abstract Metabolites are small molecules that are intermediates or products of metabolism, many of which are freely filtered by the kidneys. In addition, the kidneys have a central role in metabolite anabolism and catabolism, as well as in active metabolite reabsorption and/or secretion during tubular passage. This review article illustrates how the coupling of genomics and metabolomics in genome-wide association analyses of metabolites can be used to illuminate mechanisms underlying human metabolism, with a special focus on insights relevant to nephrology. First, genetic susceptibility loci for reduced kidney function and chronic kidney disease (CKD) were reviewed systematically for their associations with metabolite concentrations in metabolomics studies of blood and urine. Second, kidney function and CKD-associated metabolites reported from observational studies were interrogated for metabolite-associated genetic variants to generate and discuss complementary insights. Finally, insights originating from the simultaneous study of both blood and urine or by modeling intermetabolite relationships are summarized. We also discuss methodologic questions related to the study of metabolite concentrations in urine as well as among CKD patients. In summary, genome-wide association analyses of metabolites using metabolite concentrations quantified from blood and/or urine are a promising avenue of research to illuminate physiological and pathophysiological functions of the kidney. PMID: 29602398 [PubMed - in process]

Related Articles A Systems-Level View of Renal Metabolomics. Semin Nephrol. 2018 Mar;38(2):142-150 Authors: Rhee EP Abstract The measurement of select circulating metabolites such as creatinine, glucose, and cholesterol are integral to clinical medicine, with implications for diagnosis, prognosis, and treatment. Metabolomics studies in nephrology research seek to build on this paradigm, with the goal to identify novel markers and causal participants in the pathogenesis of kidney disease and its complications. This article reviews three themes pertinent to this goal. Each is rooted in long-established principles of human physiology, with recent updates enabled by metabolomics and other tools. First, the kidney has a broad and heterogeneous impact on circulating metabolites, with progressive loss of kidney function resulting in a multitude of small molecule alterations. Second, an increasing number of circulating metabolites have been shown to possess functional roles, in some cases acting as ligands for specific G-protein-coupled receptors. Third, circulating metabolites traffic through varied, and sometimes complex, interorgan circuits. Taken together, these themes emphasize the importance of viewing renal metabolomics at the systems level, recognizing the diverse origins and physiologic effects of blood metabolites. However, how to synthesize these themes and how to establish clinical relevance remain uncertain and will require further investigation. PMID: 29602397 [PubMed - in process]

Related Articles Lipidomics and Biomarker Discovery in Kidney Disease. Semin Nephrol. 2018 Mar;38(2):127-141 Authors: Afshinnia F, Rajendiran TM, Wernisch S, Soni T, Jadoon A, Karnovsky A, Michailidis G, Pennathur S Abstract Technological advances in mass spectrometry-based lipidomic platforms have provided the opportunity for comprehensive profiling of lipids in biological samples and shown alterations in the lipidome that occur in metabolic disorders. A lipidomic approach serves as a powerful tool for biomarker discovery and gaining insight to molecular mechanisms of disease, especially when integrated with other -omics platforms (ie, transcriptomics, proteomics, and metabolomics) in the context of systems biology. In this review, we describe the workflow commonly applied to the conduct of lipidomic studies including important aspects of study design, sample preparation, biomarker identification and quantification, and data processing and analysis, as well as crucial considerations in clinical applications. We also review some recent studies of the application of lipidomic platforms that highlight the potential of lipid biomarkers and add to our understanding of the molecular basis of kidney disease. PMID: 29602396 [PubMed - in process]

Related Articles The Warburg Effect in Diabetic Kidney Disease. Semin Nephrol. 2018 Mar;38(2):111-120 Authors: Zhang G, Darshi M, Sharma K Abstract Diabetic kidney disease (DKD) is the leading cause of morbidity and mortality in diabetic patients. Defining risk factors for DKD using a reductionist approach has proven challenging. Integrative omics-based systems biology tools have shed new insights in our understanding of DKD and have provided several key breakthroughs for identifying novel predictive and diagnostic biomarkers. In this review, we highlight the role of the Warburg effect in DKD and potential regulating factors such as sphingomyelin, fumarate, and pyruvate kinase muscle isozyme M2 in shifting glucose flux from complete oxidation in mitochondria to the glycolytic pathway and its principal branches. With the development of highly sensitive instruments and more advanced automatic bioinformatics tools, we believe that omics analyses and imaging techniques will focus more on singular-cell-level studies, which will allow in-depth understanding of DKD and pave the path for personalized kidney precision medicine. PMID: 29602394 [PubMed - in process]

GreenCut protein CPLD49 of Chlamydomonas reinhardtii associates with thylakoid membranes and is required for cytochrome b6 f complex accumulation. Plant J. 2018 Mar 30;: Authors: Wittkopp TM, Saroussi S, Yang W, Johnson X, Kim RG, Heinnickel ML, Russell JJ, Phuthong W, Dent RM, Broeckling CD, Peers G, Lohr M, Wollman FA, Niyogi KK, Grossman AR Abstract The GreenCut encompasses a suite of nucleus-encoded proteins with orthologs among green lineage organisms (plants, green algae), but that are absent or poorly conserved in non-photosynthetic/heterotrophic organisms. In Chlamydomonas reinhardtii, CPLD49 (Conserved in Plant Lineage and Diatoms49) is an uncharacterized GreenCut protein that is critical for maintaining normal photosynthetic function. We demonstrate that a cpld49 mutant has impaired photoautotrophic growth under high light conditions. The mutant exhibits a nearly 90% reduction in the level of the cytochrome b6 f complex (Cytb6 f), which impacts linear and cyclic electron transport, but does not compromise the ability of the strain to perform state transitions. Furthermore, CPLD49 strongly associates with thylakoid membranes where it may be part of a membrane protein complex with another GreenCut protein, CPLD38; a mutant null for CPLD38 also impacts Cytb6 f complex accumulation. We investigated several potential functions of CPLD49, with some suggested by protein homology. Our findings are congruent with the hypothesis that CPLD38 and CPLD49 are part of a novel thylakoid membrane complex that primarily modulates accumulation, but also impacts the activity of the Cytb6 f complex. Based on motifs of CPLD49 and the activities of other CPLD49-like proteins, we suggest a role for this putative dehydrogenase in the synthesis of a lipophilic thylakoid membrane molecule that influences the assembly and activity of Cytb6 f. This article is protected by copyright. All rights reserved. PMID: 29602195 [PubMed - as supplied by publisher]

Food safety using NMR-based metabolomics: Assessment of the Atlantic bluefin tuna, Thunnus thynnus, from the Mediterranean Sea. Food Chem Toxicol. 2018 Mar 27;: Authors: Cappello T, Giannetto A, Parrino V, De Marco G, Mauceri A, Maisano M Abstract Seafood is a valuable component of human diet because of its nutritional properties. The Atlantic bluefin tuna Thunnus thynnus is a scombroid fish highly appreciated as seafood worldwide. Being a top pelagic predator, concerns have been raised over human health risks due to its consumption. Therefore, herein it was comprehensively evaluated the health status and potential metabolite shifts between sexes of bluefin tuna from the Mediterranean Sea, proved to bioaccumulate environmental obesogens, namely polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) at hepatic level. To this aim, nuclear magnetic resonance (NMR)-based metabolomics was applied on liver of post-spawning tuna. Findings from this study pointed out that hepatic bioaccumulation of PCBs and OCPs induced differential metabolic disturbances between sexes, attributable to the reproductive stage at which tuna were caught. Alterations were mainly found in energy-producing metabolic pathways (with changes in acetate, acetoacetate, malonate, and lactate), amino acid (with changes in BCAA, alanine, sarcosine, and tyrosine), and lipid (with changes in choline and phosphocholine) metabolism, with activation of fatty acids biosynthesis and ketogenesis in male tuna. Overall, according to the current European legislation on maximum levels of contaminants in seafood, the consumption of bluefin tuna does not represent a risk for human health. PMID: 29601848 [PubMed - as supplied by publisher]

Related Articles Shifts in the Gut Metabolome and Clostridium difficile Transcriptome throughout Colonization and Infection in a Mouse Model. mSphere. 2018 Mar-Apr;3(2): Authors: Fletcher JR, Erwin S, Lanzas C, Theriot CM Abstract Antibiotics alter the gut microbiota and decrease resistance to Clostridium difficile colonization; however, the mechanisms driving colonization resistance are not well understood. Loss of resistance to C. difficile colonization due to antibiotic treatment is associated with alterations in the gut metabolome, specifically, with increases in levels of nutrients that C. difficile can utilize for growth in vitro. To define the nutrients that C. difficile requires for colonization and pathogenesis in vivo, we used a combination of mass spectrometry and RNA sequencing (RNA Seq) to model the gut metabolome and C. difficile transcriptome throughout an acute infection in a mouse model at the following time points: 0, 12, 24, and 30 h. We also performed multivariate-based integration of the omics data to define the signatures that were most important throughout colonization and infection. Here we show that amino acids, in particular, proline and branched-chain amino acids, and carbohydrates decrease in abundance over time in the mouse cecum and that C. difficile gene expression is consistent with their utilization in vivo. This was also reinforced by the multivariate-based integration of the omics data where we were able to discriminate the metabolites and transcripts that support C. difficile physiology between the different time points throughout colonization and infection. This report illustrates how important the availability of amino acids and other nutrients is for the initial stages of C. difficile colonization and progression of disease. Future studies identifying the source of the nutrients and engineering bacteria capable of outcompeting C. difficile in the gut will be important for developing new targeted bacterial therapeutics. IMPORTANCE Clostridium difficile is a bacterial pathogen of global significance that is a major cause of antibiotic-associated diarrhea. Antibiotics deplete the indigenous gut microbiota and change the metabolic environment in the gut to one favoring C. difficile growth. Here we used metabolomics and transcriptomics to define the gut environment after antibiotics and during the initial stages of C. difficile colonization and infection. We show that amino acids, in particular, proline and branched-chain amino acids, and carbohydrates decrease in abundance over time and that C. difficile gene expression is consistent with their utilization by the bacterium in vivo. We employed an integrated approach to analyze the metabolome and transcriptome to identify associations between metabolites and transcripts. This highlighted the importance of key nutrients in the early stages of colonization, and the data provide a rationale for the development of therapies based on the use of bacteria that specifically compete for nutrients that are essential for C. difficile colonization and disease. PMID: 29600278 [PubMed - in process]

Related Articles Coagulation cascade and complement system in systemic lupus erythematosus. Oncotarget. 2018 Mar 13;9(19):14862-14881 Authors: Liang Y, Xie SB, Wu CH, Hu Y, Zhang Q, Li S, Fan YG, Leng RX, Pan HF, Xiong HB, Ye DQ Abstract This study was conducted to (1) characterize coagulation cascade and complement system in systemic lupus erythematosus (SLE); (2) evaluate the associations between coagulation cascade, complement system, inflammatory response and SLE disease severity; (3) test the diagnostic value of a combination of D-dimer and C4 for lupus activity. Transcriptomics, proteomics and metabolomics were performed in 24 SLE patients and 24 healthy controls. The levels of ten coagulations, seven complements and three cytokines were measured in 112 SLE patients. Clinical data were collected from 2025 SLE patients. The analysis of multi-omics data revealed the common links for the components of coagulation cascade and complement system. The results of ELISA showed coagulation cascade and complement system had an interaction effect on SLE disease severity, this effect was pronounced among patients with excess inflammation. The analysis of clinical data revealed a combination of D-dimer and C4 provided good diagnostic performance for lupus activity. This study suggested that coagulation cascade and complement system become 'partners in crime', contributing to SLE disease severity and identified the diagnostic value of D-dimer combined with C4for lupus activity. PMID: 29599912 [PubMed]

Related Articles Metabolomics: From liver chiromancy to personalized precision medicine in advanced chronic liver disease. World J Hepatol. 2018 Mar 27;10(3):371-378 Authors: Procopet B, Fischer P, Farcau O, Stefanescu H Abstract Currently there is a lack of accurate biomarkers for diagnosis and prognosis in advanced liver diseases. Either the occurrence of first decompensation, or diagnosis of acute on chronic liver failure, severe alcoholic hepatitis, or hepatocellular carcinoma (HCC), none of the available biomarkers are satisfactory. Metabolomics is the newest of omics, being much closer than the others to the actual phenotype and pathologic changes that characterizes a certain condition. It deals with a much wider spectrum of low molecular weight bio-compounds providing a powerful platform for discovering novel biomarkers and biochemical pathways to improve diagnostic, prognostication and therapy. Until now metabolomics was applied in a wide spectrum of liver conditions, but the findings were contradictory. This review proposes a synthesis of the existing evidences of metabolomics use in advanced chronic liver diseases, decompensated liver cirrhosis, severe alcoholic hepatitis and HCC. PMID: 29599900 [PubMed]

Related Articles Gas chromatography-time of flight/mass spectrometry-based metabonomics of changes in the urinary metabolic profile in osteoarthritic rats. Exp Ther Med. 2018 Mar;15(3):2777-2785 Authors: Jiang H, Liu J, Qin XJ, Chen YY, Gao JR, Meng M, Wang Y, Wang T Abstract The aim of the present study was to explore changes in the urinary metabolic spectrum in rats with knee osteoarthritis, using gas chromatography-time of flight/mass spectrometry (GC-TOF/MS) to determine the metabonomic disease pathogenesis. Sprague-Dawley rats were randomly divided into the control and model groups (n=8/group), and 20 µl of 4% papain and 0.03 M L-cysteine was injected into the right knee on days 1, 3 and 7 to establish the knee osteoarthritis model. Following 14 days, urine was collected over 12 h and cartilage ultrastructural damage was assessed by hematoxylin-eosin staining. GC-TOF/MS, combined with principal component analysis, partial least squares discriminant modeling and orthogonal partial least squares discriminant modeling, was used to analyze the changes in the metabolic spectrum trajectory and to identify potential biomarkers and their related metabolic pathways. Compared with the control group, the synovial cell lining of the knee joint exhibited proliferation, inflammatory cell infiltration and collagen fiber hyperplasia in the knee osteoarthritis group. A total of 23 potential biomarkers were identified, including alanine, α-ketoglutarate, asparagine, maltose and glutamine. Furthermore, metabolomic pathogenesis of osteoarthritis may be related to disorders of amino acid metabolism, energy metabolism, fatty acid metabolism, vitamin B6 metabolism and nucleic acid metabolism. PMID: 29599826 [PubMed]