PubMed

High throughput and quantitative measurement of microbial metabolome by gas chromatography/mass spectrometry using automated alkyl chloroformate derivatization. Anal Chem. 2017 Apr 24;: Authors: Zhao L, Ni Y, Su M, Li H, Dong F, Chen W, Wei R, Zhang L, Guiraud SP, Martin FJ, Rajani C, Xie G, Jia W Abstract The ability to identify and quantify small molecule metabolites derived from gut microbial-mammalian co-metabolism is essential for the understanding of the distinct metabolic functions of the microbiome. To date, analytical protocols that quantitatively measure a complete panel of microbial metabolites in biological samples have not been established, but urgently needed by the microbiome research community. Here, we report an automated high-throughput quantitative method using a gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) platform to simultaneously measure over one hundred microbial metabolites in human serum, urine, feces and Escherichia coli cell samples within 15 minutes per sample. A reference library was developed consisting of 145 methyl and ethyl chloroformate (MCF and ECF) derivatized compounds with their mass spectral and retention index information for metabolite identification. These compounds encompass different chemical classes including fatty acids, amino acids, carboxylic acids, hydroxylic acids and phenolic acids, as well as, benzoyl and phenyl derivatives, indoles, etc., that are involved in a number of important metabolic pathways. Within an optimized range of concentrations and sample volumes, most derivatives of both reference standards and endogenous metabolites in biological samples exhibited satisfactory linearity (R2 > 0.99), good intra-batch reproducibility and acceptable stability within 6 days (RSD<20%). This method was further validated by examination of the analytical variability of 76 paired human serum, urine, and fecal samples as well as quality control samples. Our method involved using high-throughput sample preparation, measurement with automated derivatization and rapid GC/TOFMS analysis. Both techniques are well suited for microbiome metabolomics studies. PMID: 28437060 [PubMed - as supplied by publisher]

Identification of small molecules using accurate mass MS/MS search. Mass Spectrom Rev. 2017 Apr 24;: Authors: Kind T, Tsugawa H, Cajka T, Ma Y, Lai Z, Mehta SS, Wohlgemuth G, Barupal DK, Showalter MR, Arita M, Fiehn O Abstract Tandem mass spectral library search (MS/MS) is the fastest way to correctly annotate MS/MS spectra from screening small molecules in fields such as environmental analysis, drug screening, lipid analysis, and metabolomics. The confidence in MS/MS-based annotation of chemical structures is impacted by instrumental settings and requirements, data acquisition modes including data-dependent and data-independent methods, library scoring algorithms, as well as post-curation steps. We critically discuss parameters that influence search results, such as mass accuracy, precursor ion isolation width, intensity thresholds, centroiding algorithms, and acquisition speed. A range of publicly and commercially available MS/MS databases such as NIST, MassBank, MoNA, LipidBlast, Wiley MSforID, and METLIN are surveyed. In addition, software tools including NIST MS Search, MS-DIAL, Mass Frontier, SmileMS, Mass++, and XCMS(2) to perform fast MS/MS search are discussed. MS/MS scoring algorithms and challenges during compound annotation are reviewed. Advanced methods such as the in silico generation of tandem mass spectra using quantum chemistry and machine learning methods are covered. Community efforts for curation and sharing of tandem mass spectra that will allow for faster distribution of scientific discoveries are discussed. PMID: 28436590 [PubMed - as supplied by publisher]

GENOMICS AND METABOLOMICS OF POST-WEANING RETURN TO ESTRUS. Mol Reprod Dev. 2017 Apr 24;: Authors: Rempel LA, Rohrer GA, Nonneman DJ Abstract The weaning-to-estrus interval is a multifaceted trait that has the potential to substantially improve production efficiency in today's global swine industry, if variation in this measure can be reduced. Systems-biology approaches should help close the knowledge gap and increase selection tools and management strategies - such as gilt development programs, farrowing, and lactation feeding programs - to decrease the weaning-to-estrus interval. Metabolomics, the study of small compounds within biofluids and tissues, provides links between genotype and phenotype. Given the complexity and influence of the environment on the weaning-to-estrus interval, incorporating metabolomics data will provide valuable insight and guidance for future physiological as well as genetic and genomic strategies to reduce this interval, thereby improving sow productivity. This article is protected by copyright. All rights reserved. PMID: 28436551 [PubMed - as supplied by publisher]

Metabolomic approaches in the discovery of potential urinary biomarkers of drug-induced liver injury (DILI). Crit Rev Toxicol. 2017 Apr 24;:1-17 Authors: Araújo AM, Carvalho M, Carvalho F, Bastos ML, Guedes de Pinho P Abstract Drug-induced liver injury (DILI) is a major safety issue during drug development, as well as the most common cause for the withdrawal of drugs from the pharmaceutical market. The identification of DILI biomarkers is a labor-intensive area. Conventional biomarkers are not specific and often only appear at significant levels when liver damage is substantial. Therefore, new biomarkers for early identification of hepatotoxicity during the drug discovery process are needed, thus resulting in lower development costs and safer drugs. In this sense, metabolomics has been increasingly playing an important role in the discovery of biomarkers of liver damage, although the characterization of the mechanisms of toxicity induced by xenobiotics remains a huge challenge. These new-generation biomarkers will offer obvious benefits for the pharmaceutical industry, regulatory agencies, as well as a personalized clinical follow-up of patients, upon validation and translation into clinical practice or approval for routine use. This review describes the current status of the metabolomics applied to the early diagnosis and prognosis of DILI and in the discovery of new potential urinary biomarkers of liver injury. PMID: 28436314 [PubMed - as supplied by publisher]

Related Articles Deciphering the mechanism of Huang-Lian-Jie-Du-Decoction on the treatment of sepsis by formula decomposition and metabolomics: enhancement of cholinergic pathways and inhibition of HMGB-1/TLR4/NF-κB signaling. Pharmacol Res. 2017 Apr 20;: Authors: Xu D, Lv Y, Wang J, Yang M, Kong L Abstract Sepsis is the major cause of morbidity and mortality in surgical patients. Huang-Lian-Jie-Du-Decoction (HLJDD), a well-known Chinese herb formula, has long been used for the treatment of sepsis. In this investigation, by leaving one herb out each time, the four component herbs of HLJDD were reformulated to four HLJDD variants Form1-4, corresponding to the removal of Phellodendri Chinensis Cortex, Scutellariae Radix, Gardeniae Fructu and Coptidis Rhizoma, respectively. Metabolomics approach combined with histological inspection, biochemical measurement and molecular biology was used to investigate the treatment effects of HLJDD and its four variants on cecal ligation and puncture (CLP) model of sepsis, which were compared to decipher the formulating principles of HLJDD. Our results showed that HLJDD exhibit the strongest therapeutic effects in the CLP models as compared with the four variants, which could be ascribed to its most significant enhancement of cholinergic anti-inflammatory pathway and inhibition of HMGB-1/TLR4/NF-κB signaling pathway. Most of all, metabolites changed specifically between groups of HLJDD and its four variants were related with the exceptional treatment effects of HLJDD. PMID: 28434923 [PubMed - as supplied by publisher]

Related Articles Chemical Traits of Hemiparasitism in Odontites luteus. Chem Biodivers. 2017 Apr;14(4): Authors: Venditti A, Frezza C, Foddai S, Serafini M, Nicoletti M, Bianco A Abstract The study of the monoterpene glycosides content of Odontites luteus has shown the presence of a total of fifteen iridoid glucosides. The presence of compounds 1 - 5 and 7 - 10 is perfectly on-line with both the biogenetic pathway for iridoids biosynthesis in Lamiales and the current botanical classification of the species. On the other side, the presence of compounds like agnuside (6), adoxosidic acid (11), monotropein (12), 6,7-dihydromonotropein (13), methyl oleoside (14) and methyl glucooleoside (15) is of high interest because, first of all, they have never been reported before in Lamiales. In second instance, the majority of the last compounds are formally derived from a different biogenetic pathway which involves deoxyloganic acid/loganin and led to the formation of decarboxylated iridoid showing the 8β-configuration. Furthermore, a second abnormality was found during our study and this regards compounds 14 and 15 which are seco-iriodids and thus not typical for this family. The presence of these unusual compounds, biogenetically not related to species belonging to Lamiales, is a clear evidence of the metabolites transfer from the hosts. In fact, the collection area is also populated by species belonging to Oleaceae and Ericaceae which could be the possible hosts since the biosynthesis of seco-iridoids and or iridoids related to deoxyloganic acid/loganin pathway, with the 8β-configuration, is well documented in these species. PMID: 27997755 [PubMed - indexed for MEDLINE]

Related Articles Primary metabolic profiling of Egyptian broomrape (Phelipanche aegyptiaca) compared to its host tomato roots. J Plant Physiol. 2016 Oct 20;205:11-19 Authors: Hacham Y, Hershenhorn J, Dor E, Amir R Abstract Broomrape (Phelipanche aegyptiaca) is a root holoparasitic plant considered among the most destructive agricultural weeds worldwide. In order to acquire more knowledge about the metabolism of broomrape and its interaction with its tomato host, we performed primary metabolic profiling using GCMS analysis for the early developmental stage of the parasite and of infected and non-infected roots. The analysis revealed that out of 59 metabolites detected, the levels of 37 significantly increased in the parasite while the levels of 10 significantly decreased compared to the infected roots. In addition, the analysis showed that the levels of total protein in the albumin fraction, reducing sugars (representing starch) and total phenols increased by 9.8-, 4.6- and 3.3-fold, respectively, in the parasite compared to the roots. These changes suggest that P. aegyptiaca has its own metabolism that differs significantly in its regulation from those found in their host. In addition, the results have shown that the levels of most of the metabolites in the infected roots were similar to levels detected in the non-infected roots, except for seven metabolites whose levels increased in the infected versus the non-infected roots. This suggests that the parasite did not significantly affect the host primary metabolic pathways. PMID: 27589222 [PubMed - indexed for MEDLINE]

Related Articles A Pilot Metabolic Profiling Study of Patients With Neonatal Jaundice and Response to Phototherapy. Clin Transl Sci. 2016 08;9(4):216-20 Authors: Cai A, Qi S, Su Z, Shen H, Yang Y, Cai W, Dai Y Abstract Phototherapy has been widely used in treating neonatal jaundice, but detailed metabonomic profiles of neonatal jaundice patients and response to phototherapy have not been characterized. Our aim was to depict the serum metabolic characteristics of neonatal jaundice patients relative to controls and changes in response to phototherapy. A (1) H nuclear magnetic resonance (NMR)-based metabonomic approach was employed to study the metabolic profiling of serum from healthy infants (n = 25) and from infants with neonatal jaundice (n = 30) pre- and postphototherapy. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The PLS-DA and OPLS-DA model identified nine metabolites capable of distinguishing patients from controls. In addition, 28 metabolites such as β-glucose, α-glucose, valine, and pyruvate changed in response to phototherapy. This study offers useful information on metabolic disorders in neonatal jaundice patients and the effects of phototherapy on lipids, amino acid, and energy metabolism. PMID: 27306191 [PubMed - indexed for MEDLINE]

Related Articles Pharmacometabolomics in Early-Phase Clinical Development. Clin Transl Sci. 2016 Jun;9(3):128-38 Authors: Burt T, Nandal S PMID: 27127917 [PubMed - indexed for MEDLINE]

The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities. Diabetologia. 2017 Apr 22;: Authors: Brunkwall L, Orho-Melander M Abstract The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics and microbial genetics, and the need for integration of human multi-omic data (such as genetics, transcriptomics, epigenetics, proteomics and metabolomics) with microbiome data (such as strain-level variation, transcriptomics, proteomics and metabolomics) to make personalised treatments a successful future reality are discussed. PMID: 28434033 [PubMed - as supplied by publisher]

UHPLC-Q-Orbitrap-HRMS-based global metabolomics reveal metabolome modifications in plasma of young women after cranberry juice consumption. J Nutr Biochem. 2017 Apr 07;45:67-76 Authors: Liu H, Garrett TJ, Su Z, Khoo C, Gu L Abstract Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human. PMID: 28433923 [PubMed - as supplied by publisher]

Preanalytical variables for liquid chromatography-mass spectrometry (LC-MS) analysis of human blood specimens. Clin Biochem. 2017 Apr 19;: Authors: Salvagno GL, Danese E, Lippi G Abstract The use of liquid chromatography-mass spectrometry (LC-MS) for both diagnostics and research purposes is rapidly growing in clinical laboratories. As for more conventional areas of in vitro diagnostic testing, many preanalytical variables have an impact on these techniques and may hence jeopardize the quality of tests results. The leading preanalytical variables include patient preparation, the nature of the blood collection tubes and additives, interference from spurious hemolysis, sample handling and management, composition of blood tubes, contamination, as well as storage conditions. Therefore, the aim of this article is provide a narrative overview about the leading preanalytical issues which may ultimately influence LC-MS testing of human blood samples, and provide tentative indications, as for current evidence, about optimal preanalytical management of blood samples for proteomics and metabolomics studies. These general recommendations entail pre-storage centrifugation, use of appropriate tubes and additives, addition of bacteriostatic preservatives, enrichment and purification of samples, elimination of unsuitable specimens, rapid analysis or immediate storage at -70°C, and avoidance of analyzing frozen-thawed specimens. PMID: 28433611 [PubMed - as supplied by publisher]

Toward biotechnology in space: High-throughput instruments for in situ biological research beyond Earth. Biotechnol Adv. 2017 Apr 19;: Authors: Karouia F, Peyvan K, Pohorille A Abstract Space biotechnology is a nascent field aimed at applying tools of modern biology to advance our goals in space exploration. These advances rely on our ability to exploit in situ high throughput techniques for amplification and sequencing DNA, and measuring levels of RNA transcripts, proteins and metabolites in a cell. These techniques, collectively known as "omics" techniques have already revolutionized terrestrial biology. A number of on-going efforts are aimed at developing instruments to carry out "omics" research in space, in particular on board the International Space Station and small satellites. For space applications these instruments require substantial and creative reengineering that includes automation, miniaturization and ensuring that the device is resistant to conditions in space and works independently of the direction of the gravity vector. Different paths taken to meet these requirements for different "omics" instruments are the subjects of this review. The advantages and disadvantages of these instruments and technological solutions and their level of readiness for deployment in space are discussed. Considering that effects of space environments on terrestrial organisms appear to be global, it is argued that high throughput instruments are essential to advance (1) biomedical and physiological studies to control and reduce space-related stressors on living systems, (2) application of biology to life support and in situ resource utilization, (3) planetary protection, and (4) basic research about the limits on life in space. It is also argued that carrying out measurements in situ provides considerable advantages over the traditional space biology paradigm that relies on post-flight data analysis. PMID: 28433608 [PubMed - as supplied by publisher]

Metabolomics: Strategies to Define the Role of Metabolism in Virus Infection and Pathogenesis. Adv Virus Res. 2017;98:57-81 Authors: Manchester M, Anand A Abstract Metabolomics is an analytical profiling technique for measuring and comparing large numbers of metabolites present in biological samples. Combining high-throughput analytical chemistry and multivariate data analysis, metabolomics offers a window on metabolic mechanisms. Because they intimately utilize and often rewire host metabolism, viruses are an excellent choice to study by metabolomics techniques. Studies of the effects of viruses on metabolism during replication in vitro and infection in animal models or human subjects have provided novel insights into these networks and provided new targets for therapy and biomarker development. Identifying the common metabolic pathways utilized by viruses has the potential to reveal those that can be targeted by broad-spectrum antiviral and vaccine approaches. PMID: 28433052 [PubMed - in process]

Related Articles Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects. J Nutr Biochem. 2017 Apr 12;45:48-53 Authors: Hernández-Alonso P, Cañueto D, Giardina S, Salas-Salvadó J, Cañellas N, Correig X, Bulló M Abstract The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (P<.05). Moreover, cis-aconitate [intermediate of the tricarboxylic acid (TCA)] was also found decreased following PD compared with CD. Intragroup analysis showed that creatinine levels were significantly increased in PD (P=.023), whereas trimethylamine N-oxide (TMAO) was found significantly reduced following PD (P=.034). Our results suggest that chronic pistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. PMID: 28432876 [PubMed - as supplied by publisher]

Related Articles Delayed response to cold stress is characterized by successive metabolic shifts culminating in apple fruit peel necrosis. BMC Plant Biol. 2017 Apr 21;17(1):77 Authors: Gapper NE, Hertog MLATM, Lee J, Buchanan DA, Leisso RS, Fei Z, Qu G, Giovannoni JJ, Johnston JW, Schaffer RJ, Nicolaï BM, Mattheis JP, Watkins CB, Rudell DR Abstract BACKGROUND: Superficial scald is a physiological disorder of apple fruit characterized by sunken, necrotic lesions appearing after prolonged cold storage, although initial injury occurs much earlier in the storage period. To determine the degree to which the transition to cell death is an active process and specific metabolism involved, untargeted metabolic and transcriptomic profiling was used to follow metabolism of peel tissue over 180 d of cold storage. RESULTS: The metabolome and transcriptome of peel destined to develop scald began to diverge from peel where scald was controlled using antioxidant (diphenylamine; DPA) or rendered insensitive to ethylene using 1-methylcyclopropene (1-MCP) beginning between 30 and 60 days of storage. Overall metabolic and transcriptomic shifts, representing multiple pathways and processes, occurred alongside α-farnesene oxidation and, later, methanol production alongside symptom development. CONCLUSIONS: Results indicate this form of peel necrosis is a product of an active metabolic transition involving multiple pathways triggered by chilling temperatures at cold storage inception rather than physical injury. Among multiple other pathways, enhanced methanol and methyl ester levels alongside upregulated pectin methylesterases are unique to peel that is developing scald symptoms similar to injury resulting from mechanical stress and herbivory in other plants. PMID: 28431510 [PubMed - in process]

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/04/22PubMed 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.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2017/04/21PubMed 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.

The Rise of Radiomics and Implications for Oncologic Management. J Natl Cancer Inst. 2017 Jul 01;109(7): Authors: Verma V, Simone CB, Krishnan S, Lin SH, Yang J, Hahn SM Abstract Clinical medicine, particularly oncology, is progressing toward personalized care. Whereas the terms genomics, proteomics, transcriptomics, and metabolomics have dominated personalized medicine for the past couple decades, the concept of radiomics was first described in 2012. This nascent concept has major implications for personalized cancer care and involves extracting hundreds of standardized and quantifiable imaging characteristics from diagnostic computed tomography/magnetic resonance imaging images. The central hypothesis of radiomics is that these libraries of quantitative individual voxel-based variables are more sensitively associated with various clinical endpoints compared with the more qualitative radiologic, histopathologic, and clinical data more commonly utilized today. Because radiomics offers immense potential but has not reached a mainstream oncologic audience, the authors discuss herein the role of radiomics in cancer care in the future. PMID: 28423406 [PubMed - in process]

Prospective serum metabolomic profile of prostate cancer by size and extent of primary tumor. Oncotarget. 2017 Apr 01;: Authors: Huang J, Mondul AM, Weinstein SJ, Karoly ED, Sampson JN, Albanes D Abstract Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20). LC/MS-GC/MS identified 625 known compounds, and logistic regression estimated odds ratios (ORs) associated with one-standard deviation differences in log-metabolites. N-acetyl-3-methylhistidine, 3-methylhistidine and 2'-deoxyuridine were elevated in men with T2 cancers compared to controls (ORs = 1.38-1.79; 0.0002 ≤ p ≤ 0.01). By contrast, four lipid metabolites were inversely associated with T3 tumors: oleoyl-linoleoyl-glycerophosphoinositol (GPI), palmitoyl-linoleoyl-GPI, cholate, and inositol 1-phosphate (ORs = 0.49-0.60; 0.000017 ≤ p ≤ 0.003). Secondary bile acid lipids, sex steroids and caffeine-related xanthine metabolites were elevated, while two Krebs cycle metabolites were decreased, in men diagnosed with T4 cancers. Men with T2, T3, and T4 prostate cancer primaries exhibit qualitatively different metabolite profiles years in advance of diagnosis that may represent etiologic factors, molecular patterns reflective of distinct primary tumors, or a combination of both. PMID: 28423352 [PubMed - as supplied by publisher]