PubMed

Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections. J Proteome Res. 2019 Dec 13;: Authors: Afzal M, Saccenti E, Madsen M, Hansen MB, Hyldegaard O, Skrede S, Martins Dos Santos V, Norrby Teglund A, Svensson M Abstract Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal potential be useful as diagnostic and prognostic markers, as well as novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n=34) and healthy (non-infected) controls (n=24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI. Metabolite-metabolite association networks were employed to compare the metabolic profiles of NSTI patients and non-infected surgical controls. Out of 97 metabolites detected, the abundance of 33 was significantly altered in NSTI patients. Analysis of metabolite-metabolite association networks showed a more densely connected network: specifically, 20 metabolites differentially connected between NSTI and controls. A selected set of significantly altered metabolites were tested in vitro to investigate potential influence on NSTI group A streptococcal strain growth and biofilm formation. Using chemically defined media supplemented with the selected metabolites, ornithine, ribose, urea and glucuronic acid, revealed metabolite-specific effects on both bacterial growth and biofilm formation. This study identifies for the first time an NSTI specific metabolic signature with implications for optimized diagnostics and therapies. PMID: 31833369 [PubMed - as supplied by publisher]

Related Articles Berberine combined with stachyose induces better glycometabolism than berberine alone through modulating gut microbiota and fecal metabolomics in diabetic mice. Phytother Res. 2019 Dec 13;: Authors: Li CN, Wang X, Lei L, Liu MZ, Li RC, Sun SJ, Liu SN, Huan Y, Zhou T, Liu Q, Cao H, Bai GL, Han YW, Shen ZF Abstract Berberine (BBR), a small alkaloid, is used as a hypoglycemic agent in China. Stachyose (Sta), a Rehmannia glutinosa oligosaccharide, acts as a prebiotic. This study aimed to evaluate whether BBR combined with Sta produced better glycometabolism than BBR alone, and explored the effects on gut microbiota and metabolomics. Type-2 diabetic db/db mice were administered BBR (100 mg/kg), Sta (200 mg/kg), or both by gavage once daily. Glucose metabolism, the balance of α- and β-cells, and mucin-2 expression were ameliorated by combined treatment of BBR and Sta, with stronger effects than upon treatment with BBR alone. The microbial diversity and richness were altered after combined treatment and after treatment with BBR alone. The abundance of Akkermansia muciniphila was increased by combined treatment compared to treatment with BBR alone, while the levels of the metabolite all-trans-heptaprenyl diphosphate were decreased and the levels of fumaric acid were increased, which both showed a strong correlation with A. muciniphila. In summary, BBR combined with Sta produced better glycometabolism than BBR alone through modulating gut microbiota and fecal metabolomics, and may aid in the development of a novel pharmaceutical strategy for treating Type 2 diabetes mellitus. PMID: 31833107 [PubMed - as supplied by publisher]

Related Articles A Review on MS-Based Blood Biomarkers for Alzheimer's Disease. Neurol Ther. 2019 Dec;8(Suppl 2):113-127 Authors: Oeckl P, Otto M Abstract Alzheimer's disease (AD) is the most common form of neurodegenerative dementia and there is no cure to date. Biomarkers in cerebrospinal fluid (CSF) are already included in the diagnostic work-up of symptomatic patients but markers for preclinical diagnosis and disease progression are not available. Furthermore, blood biomarkers are highly appreciated because they are minimally invasive and more accessible in primary care and in clinical studies. Mass spectrometry (MS) is an established tool for the measurement of various analytes in biological fluids such as blood. Its major strength is the high selectivity which is why it is also preferred as a reference method for immunoassays. MS has been used in several studies in the past for blood biomarker discovery and validation in AD using targeted MS such as multiple/selected reaction monitoring (MRM/SRM) or unbiased approaches (proteomics, metabolomics). In this short review, we give an overview on the status of current MS-based biomarker candidates for AD in blood plasma and serum.Plain Language Summary: Plain language summary available for this article. PMID: 31833028 [PubMed]

Related Articles Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status. Metabolomics. 2019 Dec 12;16(1):6 Authors: Hanson AJ, Banks WA, Bettcher LF, Pepin R, Raftery D, Craft S Abstract INTRODUCTION: High-fat diets increase risk for Alzheimer's disease, but individuals with the risk gene APOE ε4 (E4) paradoxically have improved memory soon after high fat feeding. Little is known about how dietary lipids affect CNS lipids, especially in older adults. OBJECTIVES: We analyzed the lipidomic signature of cerebrospinal fluid (CSF) in older adults who underwent both a saline and TG infusion. We further analyzed these data by E4 carrier status. METHODS: Older adults (n = 21, age 67.7 ± 8.6) underwent a 5-h TG and saline infusion on different days in random crossover design; lumbar CSF was collected at the end of the infusion. Lipids were extracted using dichloromethane/methanol and 13 classes of lipids analyzed using the Lipidyzer platform consisting of an AB Sciex 5500 MS/MS QTraps system equipped with a SelexION for differential mobility spectrometry (DMS). Multiple reaction monitoring was used to target and quantify 1070 lipids in positive and negative ionization modes with and without DMS. RESULTS: The TG infusion increased total lipids in the CSF, including the appearance of more lipids at the detection limit in the TG samples compared to saline (Chi square p < 0.0001). The infusion increased the total level of diacylglycerols and lysophosphatidylcholines and reduced dihydroceramides. Of the possible 1070 lipids detectable, we found 348 after saline and 365 after TG infusion. Analysis using MetaboAnalyst revealed 11 specific lipids that changed; five of these lipids decreased after TG infusion, and four of them differed by E4 status, but none differed by cognitive diagnosis or sex. CONCLUSION: These results in older adults show that blood lipids affect lipid profiles in CSF and such profiles are modified by APOE status. This suggests that how the CNS handles lipids may be important in the AD phenotype. PMID: 31832778 [PubMed - in process]

Related Articles Urinary metabolites and risk of coronary heart disease: A prospective investigation among urban Chinese adults. Nutr Metab Cardiovasc Dis. 2019 Nov 05;: Authors: Yoon HS, Jeong Yang J, Rivera ES, Shu XO, Xiang YB, Calcutt MW, Cai Q, Zhang X, Li H, Gao YT, Zheng W, Yu D Abstract BACKGROUND AND AIMS: Studies have linked several metabolites to the risk of coronary heart disease (CHD) among Western populations, but prospective studies among Asian populations on the metabolite-CHD association remain limited. METHODS AND RESULTS: We evaluated the association of urinary metabolites with CHD risk among Chinese adults in a nested case-control study of 275 incident cases and 275 matched controls (127 pairs of men and 148 pairs of women). Fifty metabolites were measured by a predefined metabolomics panel and adjusted using urinary creatinine. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After adjusting for traditional CHD risk factors, urinary tryptophan showed a positive association with incident CHD: OR (95% CI) for the highest vs. lowest quartiles was 2.02 (1.15-3.56) among all study participants (p-trend = 0.02). The tryptophan-CHD association was more evident among individuals with dyslipidemia than among those without the condition (OR [95% CI] for the highest vs. lowest quartiles = 3.90 [1.86-8.19] and 0.74 [0.26-2.06], respectively; p-interaction<0.01). Other metabolites did not show significant associations with CHD risk among all study participants. However, a positive association of methionine with CHD risk was observed only among women (OR [95% CI] for the highest vs. lowest quartiles = 2.77 [1.17-6.58]; p-interaction = 0.03), and an inverse association of inosine with CHD risk was observed only among men (OR [95% CI] for the highest vs. lowest quartiles = 0.29 [0.11-0.81]; p-interaction = 0.04). CONCLUSION: Elevated urinary tryptophan may be related to CHD risk among Chinese adults, especially for those with dyslipidemia. PMID: 31831367 [PubMed - as supplied by publisher]

Related Articles Systematic analysis of the metabolites of Angelol B by UPLC-Q-TOF-MS after oral administration to rats. Chin J Nat Med. 2019 Nov;17(11):822-834 Authors: Wan MQ, Zhang YB, Liu XY, Li KM, Jia LY, Yang XW Abstract Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine (TCM), is mainly used to treat rheumatism and headache diseases. Angelol B is one of the bioactive constituents of APR with significant anti-inflammatory activity. This paper is aimed to illustrate the metabolites of angelol B in vivo. To achieve this objective, a metabolomics approach based on a rapid and accurate UPLC-Q-TOF-MS method was used to detect the metabolites of Angelol B in rat. A gradient elution system (ACN and 0.1% formic acid water) equipped with an Agilent SB-C18 column (1.8 μm, 2.1 mm × 50 mm) to complete the separation. Scanning area at m/z 100.800 operated on an electrospray ionization (ESI). The data were collected in both positive and negative ion mode and analyzed by the Masslynx 4.1 and SIMCA 13.0 software. A total of 31 metabolites including 20 phase I and 11 phase II. metabolites were identified. Their structure and fragmentation process were deduced based on the MS and MS/MS data. All of thirty-one metabolites are new compounds based on the search of SCI-Finder database. PMID: 31831129 [PubMed - in process]

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/13PubMed 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.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/13PubMed 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.

28 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 2019/12/12PubMed 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.

28 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 2019/12/12PubMed 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.

25 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 2019/12/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

25 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 2019/12/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2019/12/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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 2019/12/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Correction of Dyssynergic Defecation, but not Fiber Supplementation, Reduces Symptoms of Functional Dyspepsia in Patients With Constipation in a Randomized Trial. Clin Gastroenterol Hepatol. 2019 Dec 04;: Authors: Huaman JW, Mego M, Bendezú A, Monrroy H, Samino S, Accarino A, Saperas E, Azpiroz F Abstract BACKGROUND & AIMS: Patients with functional dyspepsia are believed to have increased sensitivity of the gastrointestinal tract, and some also have functional constipation. We investigated whether in patients with functional dyspepsia, correction of dyssynergic defecation can reduce postprandial fullness. METHODS: We performed a parallel trial at 2 referral centers in Spain, from June 2016 through January 2018 of 50 patients who fulfilled the Rome IV criteria for functional dyspepsia with postprandial distress syndrome and functional constipation and dyssynergic defecation. After a 2-week pretreatment phase, the patients were randomly assigned to groups that learned to correct dyssynergic defecation (2-3 sessions of biofeedback combined with instructions for daily exercise; n=25) or received dietary fiber supplementation (3.5 g plantago ovata per day; n=25) for 4 weeks. The primary outcome was change in postprandial abdominal fullness, measured daily on a scale of 0-10, during the last 7 days treatment phase vs the last 7 days of the pretreatment phase. Anal gas evacuations were measured (by an event marker) during the last 2 days of the pretreatment vs treatment phases. RESULTS: Biofeedback treatment corrected dyssynergic defecation in 19/25 patients; corrected dyssynergic defection reduced postprandial fullness by 22%±1% in these patients (P<.001), and reduced the number of anal evacuations by 21%±8% (P=.009). Fiber supplementation did not reduce postprandial fullness or anal evacuations (P≤.023 between groups for both parameters in the intent to treat analysis). CONCLUSIONS: Diagnosis and correction of dyssynergic defecation reduces dyspeptic symptoms by more than 20% in patients with functional dyspepsia and associated constipation. Dietary fiber supplementation does not reduce symptoms in these patients. ClinicalTrials.gov no: NCT02956187. PMID: 31811952 [PubMed - as supplied by publisher]

Related Articles Harnessing microbial metabolomics for industrial applications. World J Microbiol Biotechnol. 2019 Dec 06;36(1):1 Authors: Zhao J, Wang G, Chu J, Zhuang Y Abstract Metabolome defines a set of metabolites present in a biological sample, which provides an immediate and dynamic recording of microbes in response to genetic and/or environmental perturbations. In recent years, metabolomics in combination with other omics diagnostic tools such as genomics, transcriptomics and proteomics is focused on addressing open biological questions that accelerate our understanding of the system as a whole and boost the use of systems metabolic engineering tools in industrial settings. In this review article, we summarize the applications of metabolomics to industrial microbial fermentations with respect to the bulk production of organic acids, amino acids, enzymes, antibiotics and therapeutic proteins. In addition, future prospects regarding metabolomics-assisted research are provided. PMID: 31811524 [PubMed - in process]

Related Articles Quality Control of Preanalytical Handling of Blood Samples for Future Research: A National Survey. J Appl Lab Med. 2019 Dec 06;: Authors: Gils C, Nybo M Abstract BACKGROUND: Assessment and control of preanalytical handling of blood samples for future research are essential to preserve integrity and assure quality of the specimens. However, investigation is limited on how quality control of preanalytical handling of blood samples is performed by biobanks. METHODS: A questionnaire was sent to all Danish departments of clinical biochemistry, all Danish departments of clinical immunology, the Danish Health Surveillance Institution and the Danish Cancer Society. The questionnaire consisted of questions regarding preanalytical handling of samples for future research. The survey was carried out from October 2018 until the end of January 2019. RESULTS: A total of 22 departments (78%) replied, of which 17 (77%) performed preanalytical quality control of the blood samples. This quality control consisted of patient preparation, temperature surveillance of freezers, maintenance of centrifuges, and visual inspection for hemolysis, lipemia, and sample volume. Automated sample check for hemolysis, icterus, and lipemia interferences was performed by 41% of respondents, not performed by 50% of respondents, and 9% did not answer. The majority (55%) of the participants stated that they had no local standard operating procedure for preanalytical handling of samples for research projects. CONCLUSIONS: The preanalytical phase for blood samples obtained and preserved for future research in Denmark is highly heterogeneous, although many aspects (e.g., hemolysis, which also affects DNA analyses, metabolomics, and proteomics) seems highly relevant to document. Our findings emphasize the need to optimize and standardize best practices for the preanalytical phase for blood samples intended for use in future research projects. PMID: 31811074 [PubMed - as supplied by publisher]

Related Articles A global metabolomic insight into the oxidative stress and membrane damage of copper oxide nanoparticles and microparticles on microalga Chlorella vulgaris. Environ Pollut. 2019 Nov 27;:113647 Authors: Wang L, Huang X, Sun W, Too HZ, Laserna AKC, Li SFY Abstract To compare aquatic organisms' responses to the toxicity of copper oxide (CuO) nanoparticles (NPs) with those of CuO microparticles (MPs) and copper (Cu) ions, a global metabolomics approach was employed to investigate the changes of both polar and nonpolar metabolites in microalga Chlorella vulgaris after 5-day exposure to CuO NPs and MPs (1 and 10 mg/L), as well as the corresponding dissolved Cu ions (0.08 and 0.8 mg/L). Unchanged growth, slight reactive oxygen species production, and significant membrane damage (at 10 mg/L CuO particles) in C. vulgaris were demonstrated. A total of 75 differentiated metabolites were identified. Most metabolic pathways perturbed after CuO NPs exposure were shared by those after CuO MPs and Cu ions exposure, including accumulation of chlorophyll intermediates (max. 2.4-5.2 fold), membrane lipids remodeling for membrane protection (decrease of phosphatidylethanolamines (min. 0.6 fold) and phosphatidylcholines (min. 0.2-0.7 fold), as well as increase of phosphatidic acids (max. 1.5-2.9 fold), phosphatidylglycerols (max. 2.2-2.3 fold), monogalactosyldiacylglycerols (max. 1.2-1.4 fold), digalactosylmonoacylglycerols (max. 1.9-3.8 fold), diacylglycerols (max. 1.4 fold), lysophospholipids (max. 1.8-3.0 fold), and fatty acids (max. 3.0-6.2 fold)), perturbation of glutathione metabolism induced by oxidative stress, and accumulation of osmoregulants (max. 1.3-2.6 fold) to counteract osmotic stress. The only difference between metabolic responses to particles and those to ions was the accumulation of fatty acids oxidation products: particles caused higher fold changes (particles/ions ratio 1.9-3.0) at 1 mg/L and lower fold changes (particles/ions ratio 0.4-0.7) at 10 mg/L compared with ions. Compared with microparticles, there was no nanoparticle-specific pathway perturbed. These results confirm the predominant role of dissolved Cu ions on the toxicity of CuO NPs and MPs, and also reveal particle-specific toxicity from a metabolomics perspective. PMID: 31810715 [PubMed - as supplied by publisher]

Related Articles Advancing functional and translational microbiome research using meta-omics approaches. Microbiome. 2019 Dec 06;7(1):154 Authors: Zhang X, Li L, Butcher J, Stintzi A, Figeys D Abstract The gut microbiome has emerged as an important factor affecting human health and disease. The recent development of -omics approaches, including phylogenetic marker-based microbiome profiling, shotgun metagenomics, metatranscriptomics, metaproteomics, and metabolomics, has enabled efficient characterization of microbial communities. These techniques can provide strain-level taxonomic resolution of the taxa present in microbiomes, assess the potential functions encoded by the microbial community and quantify the metabolic activities occurring within a complex microbiome. The application of these meta-omics approaches to clinical samples has identified microbial species, metabolic pathways, and metabolites that are associated with the development and treatment of human diseases. These findings have further facilitated microbiome-targeted drug discovery and efforts to improve human health management. Recent in vitro and in vivo investigations have uncovered the presence of extensive drug-microbiome interactions. These interactions have also been shown to be important contributors to the disparate patient responses to treatment that are often observed during disease therapy. Therefore, developing techniques or frameworks that enable rapid screening, detailed evaluation, and accurate prediction of drug/host-microbiome interactions is critically important in the modern era of microbiome research and precision medicine. Here we review the current status of meta-omics techniques, including integrative multi-omics approaches, for characterizing the microbiome's functionality in the context of health and disease. We also summarize and discuss new frameworks for applying meta-omics approaches and microbiome assays to study drug-microbiome interactions. Lastly, we discuss and exemplify strategies for implementing microbiome-based precision medicines using these meta-omics approaches and high throughput microbiome assays. PMID: 31810497 [PubMed - in process]

Metabolite profiling of onion landraces and the cold storage effect. Plant Physiol Biochem. 2019 Nov 06;146:428-437 Authors: Romo-Pérez ML, Weinert CH, Häußler M, Egert B, Frechen MA, Trierweiler B, Kulling SE, Zörb C Abstract Today, commercial onion breeders focus almost entirely on conventional farming which reduces diversity in the market and leads to loss of desirable traits such as those that impact nutritional and sensory aspects of onions. A way to preserve phenotypic and genetic diversity is to re-evaluate traditional landraces to introduce their benefits to the broader public. Common onion genotypes vary greatly in their storability. In particular, temperature and relative humidity during storage have significant impact on the metabolites in onions after storage. The aim of this study was to assess changes in the metabolite profile of ten onion genotypes after five months of cold storage. In addition, a characterization of onion landraces in their fresh state was also conducted in order to compare their properties against a commercial genotype. Onion genotypes were grown under organic farming conditions. After harvest and curing, bulbs were stored for up to 22 weeks. Before and after storage, bulb samples were analyzed through targeted and untargeted methods. Out of 189 identified metabolites, 128 showed a storage effect. Mainly fructans decreased because of respiration and energy demand, while monosaccharides increased. Further, amino acids were altered in their concentration after storage with an effect on aroma precursors. Eight of the nine landraces had good storability without critical losses. In their fresh state, the onion genotypes clustered into three major groups. For instance, landraces of group III showed consistently and substantially higher levels of amino acids and certain sugars, indicating a high potential of aromatic properties in those onion landraces. PMID: 31810055 [PubMed - as supplied by publisher]