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Metabolites Oct 2017Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the... (Review)
Review
Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.
PubMed: 29065530
DOI: 10.3390/metabo7040053 -
Phytochemistry Reviews : Proceedings of... 2022Plants generate a wide variety of organic components during their different growth phases. The majority of those compounds have been classified as primary and secondary... (Review)
Review
UNLABELLED
Plants generate a wide variety of organic components during their different growth phases. The majority of those compounds have been classified as primary and secondary metabolites. Secondary metabolites are essential in plants' adaptation to new changing environments and in managing several biotic and abiotic stress. It also invests some of its photosynthesized carbon as secondary metabolites to establish a mutual relationship with soil microorganisms in that specific niche. As soil harbors both pathogenic and beneficial microorganisms, it is essential to identify some specific metabolites that can discriminate beneficial and pathogenic ones. Thus, a detailed understanding of metabolite's architectures that interact with beneficial microorganisms could open a new horizon of ecology and agricultural research. Flavonoids are used as classic examples of secondary metabolites in this study to demonstrate recent developments in understanding and realizing how these valuable metabolites can be controlled at different levels. Most of the research was focused on plant flavonoids, which shield the host plant against competitors or predators, as well as having other ecological implications. Thus, in the present review, our goal is to cover a wide range of functional and signalling activities of secondary metabolites especially, flavonoids mediated selective cross-talk between plant and its beneficial soil microbiome. Here, we have summarized recent advances in understanding the interactions between plant species and their rhizosphere microbiomes through root exudates (flavonoids), with a focus on how these exudates facilitate rhizospheric associations.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s11101-022-09806-3.
PubMed: 35221830
DOI: 10.1007/s11101-022-09806-3 -
Metabolites Jul 2023Secondary metabolites are gaining an increasing importance in various industries, such as pharmaceuticals, dyes, and food, as is the need for reliable and efficient... (Review)
Review
Secondary metabolites are gaining an increasing importance in various industries, such as pharmaceuticals, dyes, and food, as is the need for reliable and efficient methods of procuring these compounds. To develop sustainable and cost-effective approaches, a comprehensive understanding of the biosynthetic pathways and the factors influencing secondary metabolite production is essential. These compounds are a unique type of natural product which recognizes the oxidative damage caused by stresses, thereby activating the defence mechanism in plants. Various methods have been developed to enhance the production of secondary metabolites in plants. The elicitor-induced in vitro culture technique is considered an efficient tool for studying and improving the production of secondary metabolites in plants. In the present review, we have documented various biosynthetic pathways and the role of secondary metabolites under diverse environmental stresses. Furthermore, a practical strategy for obtaining consistent and abundant secondary metabolite production via various elicitation agents used in culturing techniques is also mentioned. By elucidating the intricate interplay of regulatory factors, this review paves the way for future advancements in sustainable and efficient production methods for high-value secondary metabolites.
PubMed: 37623839
DOI: 10.3390/metabo13080895 -
Plant Diversity May 2023is an important medicinal and nutraceutical herb. Although the ingredients of have been identified as polysaccharides, alkaloids, amino acids, flavonoids and...
Metabolic and transcriptomic analyses elucidate a novel insight into the network for biosynthesis of carbohydrate and secondary metabolites in the stems of a medicinal orchid .
is an important medicinal and nutraceutical herb. Although the ingredients of have been identified as polysaccharides, alkaloids, amino acids, flavonoids and bibenzyls, our understanding of the metabolic pathways that regulate the synthesis of these compounds is limited. Here, we used transcriptomic and metabolic analyses to elucidate the genes and metabolites involved in the biosynthesis of carbohydrate and several secondary metabolites in the stems of . A total of 1005 metabolites and 31,745 genes were detected in the stems of . The majority of these metabolites and genes were involved in the metabolism of carbohydrates (fructose, mannose, glucose, xylulose and starch), while some were involved in the metabolism of secondary metabolites (alkaloids, β-tyrosine, ferulic acid, 4-hydroxybenzoate and chrysin). Our predicted regulatory network indicated that five genes (, , , and ) might play vital roles in the transition from carbohydrate to alkaloid synthesis. Correlation analysis identified that six genes (, , , , and ) were involved in carbohydrate metabolism, and two genes ( and ) were involved in secondary metabolite biosynthesis. Our analyses also indicated that phosphoenol-pyruvate (PEP) was a crucial bridge that connected carbohydrate to alkaloid biosynthesis. The regulatory network between carbohydrate and secondary metabolite biosynthesis established will provide important insights into the regulation of metabolites and biological systems in species.
PubMed: 37397599
DOI: 10.1016/j.pld.2022.10.004 -
Journal of Molecular Psychiatry 2015Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes....
BACKGROUND
Traumatic stress does not only increase the risk for posttraumatic stress disorder (PTSD), but is also associated with adverse secondary physical health outcomes. Despite increasing efforts, we only begin to understand the underlying biomolecular processes. The hypothesis-free assessment of a wide range of metabolites (termed metabolite profiling) might contribute to the discovery of biological pathways underlying PTSD.
METHODS
Here, we present the results of the first metabolite profiling study in PTSD, which investigated peripheral blood serum samples of 20 PTSD patients and 18 controls. We performed liquid chromatography (LC) coupled to Quadrupole/Time-Of-Flight (QTOF) mass spectrometry. Two complementary statistical approaches were used to identify metabolites associated with PTSD status including univariate analyses and Partial Least Squares Discriminant Analysis (PLS-DA).
RESULTS
Thirteen metabolites displayed significant changes in PTSD, including four glycerophospholipids, and one metabolite involved in endocannabinoid signaling. A biomarker panel of 19 metabolites classifies PTSD with 85% accuracy, while classification accuracy from the glycerophospholipid with the highest differentiating ability already reached 82%.
CONCLUSIONS
This study illustrates the feasibility and utility of metabolite profiling for PTSD and suggests lipid-derived and endocannabinoid signaling as potential biological pathways involved in trauma-associated pathophysiology.
PubMed: 25848535
DOI: 10.1186/s40303-015-0007-3 -
Magnetic Resonance in Medicine Dec 2018To combine the metabolite-cycling technique with diffusion-weighted H-MR spectroscopy and to use the inherent water reference for compensation of motion-related signal...
PURPOSE
To combine the metabolite-cycling technique with diffusion-weighted H-MR spectroscopy and to use the inherent water reference for compensation of motion-related signal loss for improved estimation of metabolite apparent diffusion coefficients (ADCs).
METHODS
Diffusion-weighted spectra of water and metabolites were acquired simultaneously using metabolite-cycling at 3 T. The water information was used for signal correction of phase, frequency, and eddy currents, as well as for compensation of motion-induced signal loss. ADCs were estimated by 2D simultaneous fitting. The quality of ADC restoration was investigated in vitro. Subsequently, the new approach was applied in 13 subjects for enhanced metabolite ADC estimation in gray matter.
RESULTS
Metabolite-cycled diffusion H-MRS is suitable to measure metabolite and water ADCs simultaneously. The water reference facilitates signal amplitude restoration, compensating for motion-related artefacts. 2D fitting stabilizes the fitting procedure and allows the estimation of ADCs even for low signal-to-noise metabolites. Use of the motion-compensation scheme leads to estimation of smaller ADCs for virtually all metabolites (44% smaller ADC on average), to a reduction of fitting uncertainties for metabolite ADCs in individual subjects and reduced variance over the cohort (45% smaller SD on average).
CONCLUSION
Using the simultaneously acquired water signal as internal reference allows not only for compensation of phase and frequency fluctuations but also for signal amplitude restoration, and thus improved metabolite ADC estimation. Combination with 2D simultaneous fitting promises access to the diffusion properties even for low signal-to-noise metabolites. The combination of both techniques increases the specificity and sensitivity of estimated metabolite ADC values in the cohort.
Topics: Adult; Algorithms; Brain; Brain Mapping; Diffusion; Female; Gray Matter; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Spectroscopy; Male; Middle Aged; Motion; Phantoms, Imaging; Water; Young Adult
PubMed: 29687927
DOI: 10.1002/mrm.27222 -
Gut Microbes 2022The commensal bacteria that make up the gut microbiota impact the health of their host on multiple levels. In particular, the interactions taking place between the...
The commensal bacteria that make up the gut microbiota impact the health of their host on multiple levels. In particular, the interactions taking place between the microbe-associated molecule patterns (MAMPs) and pattern recognition receptors (PRRs), expressed by intestinal epithelial cells (IECs), are crucial for maintaining intestinal homeostasis. While numerous studies showed that TLRs and NLRs are involved in the control of gut homeostasis by commensal bacteria, the role of additional innate immune receptors remains unclear. Here, we seek for novel MAMP-PRR interactions involved in the beneficial effect of the commensal bacterium on intestinal homeostasis. We show that strongly activates NF-κB in IECs by releasing one or more potent activating metabolites into the microenvironment. By using drugs, chemical and gene-editing tools, we found that the released metabolite(s) enter(s) epithelial cells and activate(s) NF-κB via an ALPK1, TIFA and TRAF6-dependent pathway. Furthermore, we show that the released molecule has the biological characteristics of the ALPK1 ligand ADP-heptose. Finally, we show that induces the expression of the and genes involved in the maintenance of the intestinal barrier function and that this process is dependent on TIFA. Altogether, our data strongly suggest that the commensal promotes intestinal homeostasis by activating the ALPK1/TIFA/TRAF6 axis, an innate immune pathway exclusively described so far in the context of Gram-negative bacterial infections.
Topics: Adenosine Diphosphate; Akkermansia; Gastrointestinal Microbiome; Heptoses; Immunity, Innate; NF-kappa B; TNF Receptor-Associated Factor 6; Verrucomicrobia
PubMed: 36036242
DOI: 10.1080/19490976.2022.2110639 -
Frontiers in Pharmacology 2023ß-chloroprene (2-chloro-1,3-butadiene; CP) causes lung tumors after inhalation exposures in rats and mice. Mice develop these tumors at lower exposures than rats. In...
Using available metabolite identification and time course kinetics for β-chloroprene and its metabolite, (1-chloroethenyl) oxirane, to include reactive oxidative metabolites and glutathione depletion in a PBPK model for β-chloroprene.
ß-chloroprene (2-chloro-1,3-butadiene; CP) causes lung tumors after inhalation exposures in rats and mice. Mice develop these tumors at lower exposures than rats. In rats CP exposures cause depletion of lung glutathione (GSH). PBPK models developed to relate the appearance of mouse lung tumors with rates of CP metabolism to reactive metabolites or total amounts metabolized during exposures have been expanded to include production of reactive metabolites from CP. The extended PBPK model describes both the unstable oxirane metabolite, 2-CEO, and metabolism of the more stable oxirane, 1-CEO, to reactive metabolites via microsomal oxidation to a diepoxide, and linked production of these metabolites to a PK model predicting GSH depletion with increasing CP exposure. Key information required to develop the model were available from literature studies identifying: 1) microsomal metabolites of CP, and 2) rates of clearance of CP and 1-CEO from active microsomal preparations from mice, rats, hamsters and humans. Model simulation of concentration dependence of disproportionate increases in reactive metabolite concentrations as exposures increases and decreases in tissue GSH are consistent with the dose-dependence of tumor formation. At the middle bioassay concentrations with a lung tumor incidence, the predicted tissue GSH is less than 50% background. These simulations of reduction in GSH are also consistent with the gene expression results showing the most sensitive pathways are Nrf2-regulation of oxidative stress and GSH metabolism. The PBPK model is used to correlate predicted tissue exposure to reactive metabolites with toxicity and carcinogenicity of CP.
PubMed: 37663267
DOI: 10.3389/fphar.2023.1223808 -
Frontiers in Genetics 2019The effect of one carbon metabolism on DNA methylation has been well described, bridging nutrition, metabolism, and epigenetics. This modification is mediated by the... (Review)
Review
The effect of one carbon metabolism on DNA methylation has been well described, bridging nutrition, metabolism, and epigenetics. This modification is mediated by the metabolite S-adenosyl methionine (SAM), which is also the methyl-donating substrate of histone methyltransferases. Therefore, SAM levels that are influenced by several nutrients, enzymes, and metabolic cofactors also have a potential impact on histone methylation. Although this modification plays a major role in chromatin accessibility and subsequently in gene expression in healthy or diseased states, its role in translating nutritional changes in chromatin structure has not been extensively studied. Here, we aim to review the literature of known mechanistic links between histone methylation and the central one carbon metabolism.
PubMed: 31555321
DOI: 10.3389/fgene.2019.00764 -
Frontiers in Nutrition 2023Dysregulation of fatty acid metabolites can play a crucial role in the progression of complex diseases, such as cardiovascular disease, digestive diseases, and metabolic...
Dysregulation of fatty acid metabolites can play a crucial role in the progression of complex diseases, such as cardiovascular disease, digestive diseases, and metabolic diseases. Metabolites can have either protective or risk effects on a disease; however, the details of such associations remain contentious. In this study, we demonstrate an integrative PheWAS approach to establish high confidence, causally suggestive of metabolite-disease associations for three fatty acid metabolites, namely, omega-3 fatty acids, omega-6 fatty acids, and docosahexaenoic acid, for 1,254 disease endpoints. Metabolite-disease associations were established if there was a concordant direction of effect and significance for metabolite level and genetic risk score for the metabolite. There was enrichment for metabolite associations with diseases of the respiratory system for omega-3 fatty acids, diseases of the circulatory system and endocrine system for omega-6 fatty acids, and diseases of the digestive system for docosahexaenoic acid. Upon performing Mendelian randomization on a subset of the outcomes, we identified 3, 6, and 15 significant diseases associated with omega-3 fatty acids, omega-6 fatty acids, and docosahexaenoic acid, respectively. We then demonstrate a class of prevalence-risk relationships indicative of (de)canalization of disease under high and low fatty acid metabolite levels. Finally, we show that the interaction between the metabolites and obesity demonstrates that the degree of protection afforded by fatty acid metabolites is strongly modulated by underlying metabolic health. This study evaluated the disease architectures of three polyunsaturated fatty acids (PUFAs), which were validated by several PheWAS modes of support. Our results not only highlight specific diseases associated with each metabolite but also disease group enrichments. In addition, we demonstrate an integrative PheWAS methodology that can be applied to other components of the human metabolome or other traits of interest. The results of this study can be used as an atlas to cross-compare genetic with non-genetic disease associations for the three PUFAs investigated. The findings can be explored through our R shiny app at https://pufa.biosci.gatech.edu.
PubMed: 38303904
DOI: 10.3389/fnut.2023.1308622