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Mycobacterium vaccae is a species of nonpathogenic bacterium that lives naturally in soil. This study compared the physiological effects at a metabolomic level with autonomic nervous system responses in adults during soil-mixing activities, based on the presence or absence of M. vaccae in the soil. Twenty-nine adult participants performed soil-mixing activities for 5 minutes using sterilized soil with culture media and M. vaccae, respectively. Blood samples were drawn twice from each participant after each activity. Electroencephalograms and electrocardiograms were measured during the activity. Serum metabolites underwent metabolite profiling by gas chromatography, followed by multivariate analyses. Soil-emitted volatile organic compounds were identified using the solid-phase microextraction and gas chromatography-mass spectroscopy, followed by multivariate analyses. The volatile compound analysis revealed that the metabolites related to esters and sulfur-containing compounds are greater in soil with M. vaccae. Serum metabolomics revealed that the treatment group (soil inoculated by M. vaccae) possesses relatively higher levels of inter-alia organic and amino acids compared with the control group (soil mixed with culture media). In the treatment group, the electroencephalogram and electrocardiogram revealed that alpha band activity of the occipital lobe increases, while heart rate decreases. This study concludes that M. vaccae soil contact can affect human metabolic and autonomic reactions.

Electroencephalogram (EEG) responses and serum metabolite levels were used to investigate the effects of horticultural activities (seed-sowing) on the psychophysiological aspects of adults based on the presence or absence of the soil microorganism Streptomyces rimosus. In this case, 31 adults were subjected to seed-sowing activities using S. rimosus inoculated (experimental group) and medium (control group) soils. EEG was measured to analyze the resulting psychophysiological response, and blood samples (5 mL) were collected. The relative gamma power (RG), relative high beta (RHB), and SEF 50 and SEF 90 were significantly higher in the right than in the left occipital lobe (p < 0.05). In both occipital lobes, ratios of SMR to theta (RST), mid beta to theta (RMT), and SMR-mid beta to theta (RSMT) were high (p < 0.05). GC-TOF-MS-based serum metabolite analysis detected 33 metabolites. Compared to the control group, the experimental group showed a lower content of amino acids (except aspartic acid), lipids, and C6 sugar monomers after the activity (p < 0.05). Aminomalonic acid was decreased, and aspartic acid was increased (p < 0.05). This study confirmed a positive effect on improving the concentration and attention of adults when seed-sowing activity was performed using S. rimosus-inoculated soil.

Fermented bean products are used worldwide; most of the products are made using only a few kinds of beans. However, the metabolite changes and contents in the beans generally used during fermentation are unrevealed. Therefore, we selected four different beans (soybean

Electroencephalogram (EEG) responses and serum metabolite levels were used to investigate the effects of horticultural activities (seed-sowing) on the psychophysiological aspects of adults based on the presence or absence of the soil microorganism

This study compared the physiological effects at a metabolomics level with autonomic nervous system responses in adults during soil mixing activities, based on the presence or absence of Streptomyces rimosus in the soil. Thirty adult participants performed soil mixing activities for 5 min using sterilized soil with culture media and Streptomyces rimosus, respectively. Blood samples were drawn twice from each participant after each activity. Electroencephalograms were measured during the activity. Serum metabolites underwent metabolite profiling by gas chromatography, followed by multivariate analyses. Serum brain-derived neurotrophic factor and C-reactive protein levels were measured by Enzyme-Linked Immunosorbent Assay. Soil-emitted volatile organic compounds were identified via solid-phase microextraction and gas chromatography–mass spectroscopy, followed by multivariate analyses. The volatile compound analysis revealed that the terpenoid and benzoid compounds, geosmin, and 2-methylisoborneol were greater in soil with Streptomyces rimosus. Serum metabolomics revealed that the treatment group (soil inoculated with Streptomyces rimosus) possessed relatively higher levels of serotonin compared to the control group (soil mixed with culture media), and serum C-reactive protein levels were significantly lower in the treatment group. In the treatment group, the electroencephalogram revealed that alpha band activity of the occipital lobe increased. This study concludes that Streptomyces rimosus soil contact can positively affect human metabolic and autonomic reactions. Therefore, this pilot study confirmed the possible role of soil microorganisms in horticultural activities for psychophysiological effects in humans.

This study compared the physiological effects at a metabolomics level with autonomic nervous system responses in adults during soil mixing activities, based on the presence or absence of

Effect of water supply to metabolites in tomato fruit was compared in two soils with different nutrient conditions, i.e., either limited or excess. Two types of soil nutrient condition, type A: nutrient-limited and type B: nutrient-excess, were prepared as follows; type A is a low nutrient-containing soil without a replenishment of starved nitrogen and phosphorous, type B is a high nutrient-containing soil exceeding the recommended fertilization. Soil water was adjusted either at −30 kPa (sufficient) or −80 kPa (limited). For harvested tomato fruits, we examined primary and secondary metabolites using non-targeted mass spectrometry based metabolomics. The fruit production and leaf SPAD were greatly dependent on soil nutrient levels, by contrast, the level of lycopene remained unchanged by different levels of water and nutrient supply. The perturbation of metabolites by water supply was clear in the nutrient-excess soil. In particular, limited water supply strongly decreased primary metabolites including sugars and amino acids. We demonstrated that water stress differently shifted primary metabolites of tomato fruits in two soils with different nutrient conditions via non-targeted mass spectrometry-based metabolomics. In conclusion, we suggest that the limited water supply in soils with surplus nutrient is not a recommendable way for tomato ‘cv. Super Dotaerang’ production if fruit nutritional quality such as sugars and amino acids is in the consideration, although there was no disadvantage in fruit yield.

The yeast species Hyphopichia is common in nature and strongly competitive under harsh environmental conditions. Here, we characterized Hyphopichia burtonii KJJ43 and H. pseudoburtonii KJS14, which exhibit strong halotolerance, using genomic and transcriptomic analyses. The genomes of H. burtonii and H. pseudoburtonii comprised eight chromosomes with 85.17% nucleotide identity and significant divergence in synteny. Notably, both Hyphopichia genomes possessed extended gene families of amino acid permeases and ATP-binding cassette (ABC) transporters, whose dynamic expression patterns during osmotic stress were revealed using transcriptome profiling. Intriguingly, we found unique features of the HOG pathway activated by Hog1p even under non-osmotic stress conditions and the upregulation of cytosolic Gpd1p protein during osmotic stress. Associated with hyperfilamentation growth under high osmotic conditions, a set of genes in the FLO family with induced expression in response to NaCl, KCl, and sorbitol supplementation were identified. Moreover, comparative transcriptome analysis reveals the NaCl-specific induction of genes involved in amino acid biosynthesis and metabolism, particularly BAT2. This suggests the potential association between oxoacid reaction involving branched-chain amino acids and osmotolerance. The combined omics analysis of two Hyphopichia species provides insights into the novel mechanisms involved in salt and osmo-stress tolerance exploited by diverse eukaryotic organisms. This article is protected by copyright. All rights reserved.

Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses.Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism.For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis.Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1β, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME.Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1β secretion.

Effect of water supply to metabolites in tomato fruit was compared in two soils with different nutrient conditions, i.e., either limited or excess. Two types of soil nutrient condition, type A: nutrient-limited and type B: nutrient-excess, were prepared as follows; type A is a low nutrient-containing soil without a replenishment of starved nitrogen and phosphorous, type B is a high nutrient-containing soil exceeding the recommended fertilization. Soil water was adjusted either at -30 kPa (sufficient) or -80 kPa (limited). For harvested tomato fruits, we examined primary and secondary metabolites using non-targeted mass spectrometry based metabolomics. The fruit production and leaf SPAD were greatly dependent on soil nutrient levels, by contrast, the level of lycopene remained unchanged by different levels of water and nutrient supply. The perturbation of metabolites by water supply was clear in the nutrient-excess soil. In particular, limited water supply strongly decreased primary metabolites including sugars and amino acids. We demonstrated that water stress differently shifted primary metabolites of tomato fruits in two soils with different nutrient conditions

To investigate antioxidant and anti-inflammatory effects of aWe measured levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and inflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW264.7 cells at various PINE concentrations (25, 50 and 100 μg/mL; but 6.25, 12.5 and 25 μg/mL for interleukin-1β and prostaglandin EPINE 100 μg/mL significantly decreased ROS (ICPINE exerts antioxidant and anti-inflammatory effects by inhibiting the production of inflammatory mediators. Identified flavonoids such as taxifolin and quercetin glucoside can be attributed to effect of PINE.

Plant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua(AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC−LTQ−Orbitrap–MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.

Alzheimer's disease (AD) is the most common dementia characterized by the excessive accumulation of amyloid-beta (Aβ) and tau aggregates, as well as neuronal damage and neuroinflammation. Metabolic disruption in AD has been noticed because metabolite alterations closely correlate with Aβ neuropathology and behavioral phenotypes. Accordingly, controlling various neuropathological processes and metabolic disruption is an efficient therapeutic strategy for AD treatment. In this study, we evaluated the effects of a combination of Cuscuta seeds and Lactobacillus paracasei NK112 (CCL01) on AD neuropathology and altered metabolism in five familial AD (5xFAD) transgenic mice and neuronal cell cultures. First, we observed that CCL01 exerted neuroprotective effects in HT22 hippocampal neurons and primary cultured neurons. CCL01 ameliorated memory decline and protected synapses and neuronal survival in 5xFAD mice. These effects were related to the inhibition of tau phosphorylation. CCL01 also inhibited the activation of mitogen-activated protein kinase (MAPK) signaling and neuroinflammatory processes. Moreover, the metabolite profile-particularly characterized by altered phospholipid metabolism-was significantly changed in the 5xFAD group, while CCL01 partly restored the alteration. Lysophosphatidylcholine (lysoPC), the levels of which were higher in the brains of 5xFAD mice, exerted neurotoxicity in vitro, whereas CCL01 protected neurons from lysoPC-induced toxicity by regulating MAPK signaling. Additionally, CCL01 administration reduced gut inflammation in the 5xFAD mice. In summary, we demonstrated that CCL01 improved the memory function of 5xFAD mice by protecting neurons against Aβ- and lysoPC-induced toxicity through the regulation of MAPK signaling, neuroinflammation, tau phosphorylation, and gut inflammation, suggesting the potential of CCL01 as treatment for AD.

Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance., Here, the authors report the results of a longitudinal multi-omics trial of the use of fecal microbiota transplantation (FMT) to ameliorate diarrhea and restore gut microbial composition in 57 growing calves, and find that oral FMT induces alterations in the gut microbiota correlate with the remission of diarrhea and improves the growth performance of the cattle.

Cucumber (Cucumis sativus L.) is consumed worldwide and various cultivars have been developed to enhance fruit quality. However, few studies have comprehensively evaluated the quality of various cultivars. We carried out a metabolomics approach to study the three different cucumber cultivars (Chuichung, White Dadagi, and Mini) and their parts (peel and flesh) coupled with antioxidant activities. The amino acids, sugars, flavonoids, carotenoids, and chlorophylls were upregulated in Mini flesh; however, in the case of peel, they were highly expressed in Chuichung. The highest antioxidant activity was observed in the peel of Chuichung and flesh of Mini. Through correlation analysis between metabolites and antioxidant activity, apigenin and quercetin derivatives, chlorophyll a, chlorophyll b, lutein, α-carotene, and β-carotene were found to be significantly positively correlated with antioxidant activity. To understand the metabolism of these compounds, we performed a comprehensive pathway analysis using a metabolomics approach and analysis of associated gene expression. In secondary metabolism, the expression levels of carotenoid-related genes (15-cis-phytoene synthase and ζ-carotene desaturase) and chlorophyll-related genes (protochlorophyllide reductase and glutamyl-tRNA reductase) were consistent with the metabolome analysis data. Collectively, carotenoid and chlorophyll metabolism were upregulated in Chuichung peel and Mini flesh, which had the highest antioxidant activity in each part. These bioactive compounds can be used as biomarkers of commercial cucumber fruit quality. Accordingly, this study offers integrative insights into the quality of different cucumber cultivars and explores valuable metabolites and genes that are helpful in improving quality with functional properties.

This paper proposes positioning and trajectory tracking for Caterpillar Vehicles (CVs) in unknown environments. To do these tasks, the following are performed. Firstly, a system modeling of the Caterpillar Vehicle is presented. Secondly, solving the complicated tracking control problem in unknown environments is a challenging mission. Therefore, to guarantee the Caterpillar Vehicle system to be strong robustness against external disturbances in the unknown environments, a MIMO robust servo controller for tracking the desired trajectory is designed by using a Linear Shift Invariant Differential (LSID) operator. The CVs are able to accomplish various tasks in dangerous places where workers cannot enter. Thirdly, the positioning of the CV can be obtained using a Simultaneous Localization and Mapping (SLAM) method. This paper develops perfectly the SLAM algorithm for positioning of the CV based on laser sensor Lidar. The main advantage of this method is that it does not need to use more landmarks. Landmarks can be obtained from the unknown environment. Thus, the CV can work even in unknown environments and unsafe places. Finally, to verify the effectiveness of the proposed MIMO robust servo controller and the SLAM positioning algorithm, the experimental results are presented. The experimental results demonstrate the adequate tracking performance of the proposed MIMO robust servo controller in the unknown environment.

Background: Ginseng berries (GBs) show temporal metabolic variations among different maturation stages, determining their organoleptic and functional properties. Methods: We analyzed metabolic variations concomitant to five different maturation stages of GBs including immature green (IG), mature green (MG), partially red (PR), fully red (FR), and overmature red (OR) using mass spectrometry (MS)–based metabolomic profiling and multivariate analyses. Results: The partial least squares discriminant analysis score plot based on gas chromatography–MS datasets highlighted metabolic disparity between preharvest (IG and MG) and harvest/postharvest (PR, FR, and OR) GB extracts along PLS1 (34.9%) with MG distinctly segregated across PLS2 (18.2%). Forty-three significantly discriminant primary metabolites were identified encompassing five developmental stages (variable importance in projection > 1.0, p 1.0, p

Appropriate adjustment of various microclimatic and nutrient conditions can improve crop productivity under greenhouse cultivation. Here, we performed non-targeted profiling to investigate metabolite variation in tomato fruits following different supplementary LED lighting (SL) (red: R; blue: B; and a combination of red and blue light: RB, for 1 h/day and 6 h/day per condition) and mineral nutrient supply (N, K, Mg). The different SL treatments affected metabolite variation in tomato fruits more significantly than mineral nutrients. Importantly, regulating the SL period induced a more distinct metabolite composition in tomato fruits than that induced by varying the SL sources. Tomato fruits cultivated under RB for 6 h/day had a relatively higher content of sugar derivatives, especially sucrose, thus influencing the gustatory characteristics of the fruit. In contrast, fruit from tomatoes cultivated under RB for 1 h/day showed a distinctive increase in the abundance of amino acids, organic acids, and several secondary metabolites, adding to its nutritional quality. Intriguingly, the different mineral supplements elicited discriminant metabolic variation in tomato fruits cultivated under reduced levels of mineral supply; however, the effects were insignificant under enhanced levels of mineral supply. Specifically, reduced level in nitrogen supply resulted in a lower abundance of amino acids, whereas reduced level in potassium supply increased metabolite levels including amino acids, sugars, and fatty acids in tomato fruits. In the present study, we employed a non-targeted metabolomics approach to unravel the effects of microclimatic parameters and mineral nutrients on fruit quality parameters of tomato plants, by which regulating the period of SL and reducing the potassium concentration were suggested to improve different nutritional qualities.

Xanthomonas oryzae pv. oryzae (Xoo) is a vascular pathogen that causes leaf blight in rice, leading to severe yield losses. Since the usage of chemical control methods has not been very promising for the future disease management, it is of high importance to systematically gain new insights about Xoo virulence and pathogenesis, and devise effective strategies to combat the rice disease. To do this, we reconstructed a genome‐scale metabolic model of Xoo (iXOO673) and validated the model predictions using culture experiments. Comparison of the metabolic architecture of Xoo and other plant pathogens indicated that the Entner–Doudoroff pathway is a more common feature in these bacteria than previously thought, while suggesting some of the unique virulence mechanisms related to Xoo metabolism. Subsequent constraint‐based flux analysis allowed us to show that Xoo modulates fluxes through gluconeogenesis, glycogen biosynthesis, and degradation pathways, thereby exacerbating the leaf blight in rice exposed to nitrogenous fertilizers, which is remarkably consistent with published experimental literature. Moreover, model‐based interrogation of transcriptomic data revealed the metabolic components under the diffusible signal factor regulon that are crucial for virulence and survival in Xoo. Finally, we identified promising antibacterial targets for the control of leaf blight in rice by using gene essentiality analysis., We reconstructed a genome‐scale metabolic model of the rice leaf pathogen Xanthomonas oryzae for understanding its virulence and survival, and identified promising antibacterial targets.

Background Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites. Results Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson’s correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity. Conclusions This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.

A metabolomics approach was used to profile metabolites of Panax notoginseng fermented with Aspergillus cristatus in two ways, liquid-state fermentation (LF-P) and solid-state fermentation (SSF-P) and examine metabolite markers representing antioxidant activity and skin anti-aging. Protopanaxadiol (PPD) and protopanaxatriol (PPT) contents were higher in SSF-P than in LF-P and showed a multiplicative increase over the fermentation period of four days. PPD and PPT levels also correlated with antioxidant and anti-aging effects in skin, based on the mRNA expression of dermal extracellular matrix components. In the bioactivity validation assays, PPD and PPT significantly improved the expression of type-I collagen, fibrillin-1, and elastin in human dermal fibroblasts from both young and old subjects; these were comparable with the effects of the SSF-P extracts. Overall, our results suggest that changes in the metabolites of P. notoginseng fermented with A. cristatus enhance the quality and availability of bioactive compounds associated with skin anti-aging.

Fermented bean products are used worldwide; most of the products are made using only a few kinds of beans. However, the metabolite changes and contents in the beans generally used during fermentation are unrevealed. Therefore, we selected four different beans (soybean, Glycine max, GM; wild soybean, Glycine soja, GS; common bean, Phaseolus vulgaris, PV; and hyacinth bean, Lablab purpureus, LP) that are the most widely consumed and fermented with Aspergillus oryzae. Then, metabolome and multivariate statistical analysis were performed to figure out metabolite changes during fermentation. In the four beans, carbohydrates were decreased, but amino acids and fatty acids were increased in the four beans as they fermented. The relative amounts of amino acids were relatively abundant in fermented PV and LP as compared to other beans. In contrast, isoflavone aglycones (e.g., daidzein, glycitein, and genistein) and DDMP-conjugated soyasaponins (e.g., soyasaponins βa and γg) were increased in GM and GS during fermentation. Notably, these metabolite changes were more significant in GS than GM. In addition, the increase of antioxidant activity in fermented GS was significant compared to other beans. We expect our research provides a basis to extend choice for bean fermentation for consumers and food producers.

Bacterial-fungal metabolite trade-offs determine their ecological interactions. We designed a non-obligate pairwise metabolite cross-feeding (MCF) between Bacillus amyloliquefaciens and Aspergillus oryzae. Cross-feeding Aspergillus metabolites (MCF-1) affected higher growth and biofilm formation in Bacillus. LC-MS/MS-based multivariate analyses (MVA) showed variations in the endogenous metabolite profiles between the cross-fed and control Bacillus. We observed and validated that Aspergillus-derived oxylipins were rapidly depleted in Bacillus cultures concomitant with lowered secretion of cyclic lipopeptides (CLPs). Conversely, Bacillus extracts cross-fed to Aspergillus (MCF-2) diminished its mycelial growth and conidiation. Fungistatic effects of Bacillus-derived cyclic surfactins were temporally reduced following their hydrolytic linearization. MVA highlighted disparity between the cross-fed (MCF-2) and control Aspergillus cultures with marked variations in the oxylipin levels. We conclude that the pairwise MCF selectively benefitted Bacillus while suppressing Aspergillus, which suggests their ammensalic interaction. Widening this experimental pipeline across tailored communities may help model and simulate BFIs in more complex microbiomes.

Annona muricata (AM) is evergreen plant of the Annonaceae family and known to have anticancer and antidiabetic effects. However, anti-diabetic mechanisms of AM extracts (AME) associated with hepatic glucose regulation and lipid metabolism remain unclear. In this study, we investigated the protective effect of AME extracted on hepatic damage in diabetic mice. Diabetes was induced by a high-fat diet with two-times streptozotocin (STZ) injection (60 mg/kg BW) in C57BL/6 male mice. The diabetic mice were daily administered with AME (50 or 100 mg/kg BW) by gavage for 9 weeks. Biomarkers related to energy metabolism and insulin signaling were examined to identify the effect of AME on hyperglycemia induced hepatic damage. AME supplementation reduced levels of FBG, HbA1c, HOMA-IR and hepatic lipid profiles as well as enhanced insulin signaling by increased the protein levels of IRS-1 accompanied GLUT2 in diabetic mice. Especially low dose of AME showed the beneficial effect of reducing oxidative stress (4-HNE, protein carbonyls, Nrf2, NQO1) and improved hepatic morphology demonstrated by lipid droplets along with upregulation of lipophagy (pAMPK, p-mTOR/mTOR, LC3-2/LC3-1) in diabetic mice. Moreover, AME supplementation ameliorated hepatic lipid metabolism (FAS, SREBP1c, C/EBPα, PPARγ, CPT1A, PPARα) and energy metabolism (pAMPK, PGC1α) in diabetic mice. Taken together, this study suggested that AME could be helpful to prevent hepatic abnormality by regulation of insulin signaling associated with energy metabolism and autophagy in diabetes.

Many indigenous Korean plants have been used in medicinal preparations and health-promoting foods. These plant species contain beneficial metabolites with various bioactivities, such as antioxidant and anti-inflammatory activities. Herein, we suggest a new screening strategy using metabolomics to explore the bioactive compounds in 50 Korean plants. Secondary metabolites were analyzed using UHPLC-LTQ-Orbitrap-MS/MS. The plant extracts were subjected to antioxidant and anti-inflammatory assays. We identified metabolites that contributed to bioactivities according to the results of bioassays and multivariate analyses. Using Pearson’s correlation, phenolics (e.g., casuarictin, 3-O-methylellagic acid) showed positive correlation with antioxidant activity, while biflavonoids (e.g., amentoflavone, rosbustaflavone) were correlated with nitric oxide (NO) inhibition activity. To compensate for the limitation of this new strategy, we further validated these by investigating three parts (branches, fruits, leaves) of Platycladus orientalis which showed high activities on both bioassays. Unlike the above observation, we identified significantly different metabolites from different parts, which was not the results of bioassays. In these validation steps, interestingly, biflavonoids (e.g., robustaflavone, sciadopitysin) contributed to both activities in P. orientalis. The findings of this work suggest that new strategy could be more beneficial in the identification of bioactive plant species as well as that of their corresponding bioactive compounds that impart the bioactivity.

Annona muricata (AM) is evergreen plant of the Annonaceae family and known to have anticancer and antidiabetic effects. However, anti-diabetic mechanisms of AM extracts (AME) associated with hepatic glucose regulation and lipid metabolism remain unclear. In this study, we investigated the protective effect of AME extracted on hepatic damage in diabetic mice. Diabetes was induced by a high-fat diet with two-times streptozotocin (STZ) injection (60 mg/kg BW) in C57BL/6 male mice. The diabetic mice were daily administered with AME (50 or 100 mg/kg BW) by gavage for 9 weeks. Biomarkers related to energy metabolism and insulin signaling were examined to identify the effect of AME on hyperglycemia induced hepatic damage. AME supplementation reduced levels of FBG, HbA1c, HOMA-IR and hepatic lipid profiles as well as enhanced insulin signaling by increased the protein levels of IRS-1 accompanied GLUT2 in diabetic mice. Especially low dose of AME showed the beneficial effect of reducing oxidative stress (4-HNE, protein carbonyls, Nrf2, NQO1) and improved hepatic morphology demonstrated by lipid droplets along with upregulation of lipophagy (pAMPK, p-mTOR/mTOR, LC3-2/LC3-1) in diabetic mice. Moreover, AME supplementation ameliorated hepatic lipid metabolism (FAS, SREBP1c, C/EBPα, PPARγ, CPT1A, PPARα) and energy metabolism (pAMPK, PGC1α) in diabetic mice. Taken together, this study suggested that AME could be helpful to prevent hepatic abnormality by regulation of insulin signaling associated with energy metabolism and autophagy in diabetes.

Yams (Dioscorea spp.) are cultivated and consumed as edible tubers, while their leaves are discarded as waste or burned with negative environmental impact. Herein, the metabolites of two yam species (Danma, DAN, Dunggeunma, DUN), harvested in June, July, and August, were profiled using GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS and the antioxidant activity of the extracts was evaluated to stimulate the utilization of yam leaves as a by-product. We observed that the relative levels of amino acids, organic acids, sugars, and saponins decreased linearly with prolonged harvest time, while fatty acid, phenanthrene, and flavonoid levels gradually increased. Furthermore, the leaf extracts obtained in August exhibited the highest antioxidant activity. To determine the antioxidant-contributing metabolites, OPLS-DA was performed for the leaf metabolites of DAN and DUN leaves harvested in August. Hydroxytyrosol-glucoside, apigenin-rhamnoside, and rutin were more abundant in DUN, while luteolin, phenanthrene derivatives, epicatechin, and kaempferide were relatively higher in DAN and their respective metabolites were positively correlated with the antioxidant activity. Moreover, secondary metabolites were more abundant in the leaves than in the roots, and consequently, the antioxidant activity of the former was also higher. Overall, the potential value of yam leaves as a renewable source of bioactive compounds is proposed.

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease, and becomes increasingly prevalent with age. α-Synuclein (α-syn) forms the major filamentous component of Lewy bodies, which are pathological hallmarks of α-synucleinopathies such as PD. We evaluated the neuroprotective effects of MT101-5, a standardized herbal formula that consists of an ethanolic extract of Genkwae Flos, Clematidis Radix, and Gastrodiae Rhizoma, against α-synuclein-induced cytotoxicity in vivo. MT101-5 protected against behavioral deficits and loss of dopaminergic neurons in human α-syn-overexpressing transgenic mice after treatment with 30 mg/kg/day for 5 months. We investigated transcriptomic changes within MT101-5 mechanisms of action (MOA) suppressing α-syn aggregation in an α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic PD. We found that inhibition of α-syn fibril formation was associated with changes in transcripts in mitochondrial biogenesis, electron transport, chaperones, and proteasomes following treatment with MT101-5. These results suggest that the mixed herbal formula MT101-5 may be used as a pharmaceutical agent for preventing or improving PD.

Yams (Dioscorea spp.) are cultivated and consumed as edible tubers, while their leaves are discarded as waste or burned with negative environmental impact. Herein, the metabolites of two yam species (Danma, DAN; Dunggeunma, DUN), harvested in June, July, and August, were profiled using GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS and the antioxidant activity of the extracts was evaluated to stimulate the utilization of yam leaves as a by-product. We observed that the relative levels of amino acids, organic acids, sugars, and saponins decreased linearly with prolonged harvest time, while fatty acid, phenanthrene, and flavonoid levels gradually increased. Furthermore, the leaf extracts obtained in August exhibited the highest antioxidant activity. To determine the antioxidant-contributing metabolites, OPLS-DA was performed for the leaf metabolites of DAN and DUN leaves harvested in August. Hydroxytyrosol-glucoside, apigenin-rhamnoside, and rutin were more abundant in DUN, while luteolin, phenanthrene derivatives, epicatechin, and kaempferide were relatively higher in DAN and their respective metabolites were positively correlated with the antioxidant activity. Moreover, secondary metabolites were more abundant in the leaves than in the roots, and consequently, the antioxidant activity of the former was also higher. Overall, the potential value of yam leaves as a renewable source of bioactive compounds is proposed.

Numerous varieties of doenjang are manufactured by many food companies using different ingredients and fermentation processes, and thus, the qualities such as taste and flavor are very different. Therefore, in this study, we compared many products, specifically, 19 traditional doenjang (TD) and 17 industrial doenjang (ID). Subsequently, we performed non-targeted metabolite profiling, and multivariate statistical analysis to discover distinct metabolites in two types of doenjang. Amino acids, organic acids, isoflavone aglycones, non-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4- one) soyasaponins, hydroxyisoflavones, and biogenic amines were relatively abundant in TD. On the contrary, contents of dipeptides, lysophospholipids, isoflavone glucosides and DDMP-conjugated soyasaponin, precursors of the above-mentioned metabolites, were comparatively higher in ID. We also observed relatively higher antioxidant, protease, and β-glucosidase activities in TD. Our results may provide valuable information on doenjang to consumers and manufacturers, which can be used while selecting and developing new products.

In this study, we investigated the altered enzymatic activities and metabolite profiles of koji fermented using varying permutations of Aspergillus oryzae and/or Bacillus amyloliquefaciens. Notably, the protease and β-glucosidase activities were manifold increased in co-inoculated (CO) koji samples (co-inoculation of A. oryzae and B. amyloliquefaciens). Furthermore, gas chromatography-mass spectrometry (GC-MS)-based metabolite profiling indicates that levels of amino acids, organic acids, sugars, sugar alcohols, fatty acids, nucleosides, and vitamins were distinctly higher in CO, SA (sequential inoculation of A. oryzae, followed by B. amyloliquefaciens), and SB (sequential inoculation of B. amyloliquefaciens, followed by A. oryzae). The multivariate principal component analysis (PCA) plot based on GC-MS datasets indicated a clustered pattern for MA and MB (koji samples inoculated either with A. oryzae or B. amyloliquefaciens) across PC2 (20.0%). In contrast, the CO, SA, and SB metabolite profiles displayed segregated patterns across PLS1 (22.2%) and PLS2 (21.1%) in the partial least square discriminant analysis (PLS-DA) model. Intriguingly, the observed disparity in the levels of primary metabolites was engendered largely by higher relative levels of sugars and sugar alcohols in MA, SA, and CO koji samples, which was commensurate with the relative amylase activities in respective samples. Collectively, the present study emphasizes the utility of integrated biochemical and metabolomic approaches for achieving the optimal permutation of fermentative inocula for industrial koji preparation.

Tomato is one of the world's most consumed vegetables, and thus, various cultivars have been developed. Therefore, metabolic differences and nutrient contents of various tomatoes need to be discovered. To do so, we performed metabolite profiling along with evaluation of morphological and physicochemical properties of five representative tomato types. Common tomato cultivars, bigger and heavier than other tomatoes, contained higher levels of amino acids, organic acids, and lipids. On the contrary, cherry tomato cultivars contained a higher proportion of phenylpropanoids, lycopene, β-carotene, and α-carotene than the other tomatoes. Also, the highest antioxidant activity and total phenolic and flavonoid contents were observed in cherry tomato cultivars. Furthermore, to understand metabolic distributions in various tomato cultivars, we constructed a metabolic pathway map. The higher metabolic flux distribution of most primary metabolite synthetic pathways was observed in common tomatoes, while cherry tomato cultivars showed a significantly elevated flux in secondary metabolite synthetic pathways. Accordingly, these results provide valuable information of different characteristics in various tomatoes, which can be considered while purchasing and improving tomato cultivars.

Ethnopharmacological relevance Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear. Aim of the study In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS). Materials and methods A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively. Results The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice. Conclusion AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.

Doenjang and ganjang are secondary fermented soybean products from meju (primary fermented product) following a complex fermentation process that separates the products into solid (doenjang) and liquid (ganjang) states. We performed a comparative study on gas chromatography mass spectrometry-(GC-MS) and liquid chromatography mass spectrometry-(LC-MS) based metabolite profiling with fungal and bacterial microbial community analysis of doenjang and ganjang during fermentation. Metabolite profiling and microbial community data showed distinct patterns, depending on the fermentation process. The relative levels of metabolic patterns were similar and most of the microorganisms produced halophilic or halotolerant microbes during the fermentation period in doenjang and ganjang. In the doenjang end products, isoflavones, soyasaponins, and amino acids were largely distributed and Debaryomyces and Staphylococcus were dominant, whereas the biogenic amine and phenylpropanoid contents were highly distributed in the ganjang end products, with higher levels of Meyerozyma and Tetragenococcus. Our results demonstrate that the quality of doenjang and ganjang is predominantly influenced by the microbiome and by metabolite changes during fermentation. Moreover, the present study provides a platform for comparing samples in different states.

Doenjang and ganjang are secondary fermented soybean products from meju (primary fermented product) following a complex fermentation process that separates the products into solid (doenjang) and liquid (ganjang) states. We performed a comparative study on gas chromatography mass spectrometry-(GC-MS) and liquid chromatography mass spectrometry-(LC-MS) based metabolite profiling with fungal and bacterial microbial community analysis of doenjang and ganjang during fermentation. Metabolite profiling and microbial community data showed distinct patterns, depending on the fermentation process. The relative levels of metabolic patterns were similar and most of the microorganisms produced halophilic or halotolerant microbes during the fermentation period in doenjang and ganjang. In the doenjang end products, isoflavones, soyasaponins, and amino acids were largely distributed and Debaryomyces and Staphylococcus were dominant, whereas the biogenic amine and phenylpropanoid contents were highly distributed in the ganjang end products, with higher levels of Meyerozyma and Tetragenococcus. Our results demonstrate that the quality of doenjang and ganjang is predominantly influenced by the microbiome and by metabolite changes during fermentation. Moreover, the present study provides a platform for comparing samples in different states.

Pinus thunbergii Parl. (PTP) has traditionally been used for edible and medicinal purposes to treat several disorders, including diabetes and neuralgia. Therefore, this study sought to evaluate the inhibitory effects of PTP leaf ethanol extracts on acute inflammation. Moreover, the reactive oxygen species (ROS) scavenging activity, superoxide dismutase (SOD) activity, lipopolysaccharide (LPS)-induced nitric oxide (NO) generation, and H2O2-induced lipid peroxidation capacity of PTP were assessed in vitro in RAW 264.7 macrophages. Our results suggest that PTP prevents cell damage caused by oxidative free radicals and downregulates the expression of LPS-induced inflammation-associated factors including inducible nitric oxidase synthetase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). PTP inhibited NO production by 53.5% ( P < 0.05 ) and iNOS expression by 71.5% ( P < 0.01 ) at 100 µg/mL. PTP at 100 µg/mL also inhibited ROS generation by 58.2% ( P < 0.01 ) and SOD activity by 29.3%, as well as COX-2 expression by 83.3% ( P < 0.01 ) and PGE2 expression by 98.6% ( P < 0.01 ). The anti-inflammatory effects of PTP were confirmed in vivo using an arachidonic acid (AA)-induced ear edema mouse model. Ear thickness and myeloperoxidase (MPO) activity were evaluated as indicators of inflammation. PTP inhibited edema formation by 64.5% ( P < 0.05 ) at 1.0 mg/ear. A total of 16 metabolites were identified in PTP extracts and categorized into subgroups, including two phenolic acids (mainly quinic acid), seven flavonoids, five lignans, one sesquiterpenoid, and one long-chain fatty acid. Therefore, our results suggest that PTP possesses anti-inflammatory properties.

Ginseng berry pomace (GBP) is a byproduct of ginseng berry processing and is rich in numerous bioactive components, including ginsenosides and their derivatives. The application of GBP as a beneficial biomaterial is currently limited. In this study, we aimed to evaluate their potential as a promising source of bioactive compounds using metabolite profiling. The GBP obtained after different ultra-high-pressure (UHP) treatments was analyzed by GC-TOF-MS and UHPLC-LTQ-Orbitrap-MS/MS. In multivariate analyses, we observed a clear demarcation between the control and UHP-treated groups. The results demonstrated that the relative abundance of primary metabolites and a few ginsenosides was higher in the control, whereas UHP treatment contained higher levels of fatty acids and sugars. Furthermore, GBPs were fractionated using different solvents, followed by UHPLC-LTQ-Orbitrap-MS/MS analyses. The heatmap revealed that phenolics (e.g., quercetin, kaempferol) and fewer polar ginsenosides (e.g., F4, Rh2) were abundant in the ethyl acetate fraction, whereas the levels of lignans (e.g., 7-hydroxysecoisolariciresinol, syringaresinol) and fatty acids (e.g., trihydroxy-octadecenoic acid, oxo-dihydroxy-octadecenoic acid) were high in chloroform. Correlation analysis showed that phenolics, less polar ginsenosides, and fatty acids were positively correlated with the antioxidant activity of GBP. Our study highlights GBP as a functional ingredient for the development of high-quality ginseng berry products.

Objective: To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 yrs.Subjects and Methods: An elderly cohort of T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort.Results: From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957).Conclusions: Our study suggests that multi-biomarkers may be useful for predicting DME in elderly T2DM patients.

Helicobacter pylori (H. pylori) alters metabolism during the gastric carcinogenesis process. This study aimed to determine the metabolites in the gastric mucosa according to the status of the H. pylori infection. Patients who visited the outpatient clinic for a gastroscopy and H. pylori tests were included. Gas chromatography–time-of-flight mass spectrometry (GC-TOF-MS) analysis was performed using gastric biopsied specimens from the corpus. Twenty-eight discriminative metabolites were found in the gastric mucosa of 10 patients with current H. pylori infection, in 15 with past infection, and in five with no infection history. The relative abundances (RAs) of amino acids and sugars/sugar alcohols were higher in patients with no infection history than in patients with current or past infection. The current infection group showed higher RAs of organic acids and lower RAs of fatty acids and lipids compared with the other groups. The RA of inosine was highest in the past infection group. Based on GC-TOF-MS analysis findings, metabolites differed not only between the infected and non-infected patients, but also between those with and without infection history. Amino acid and sugars/sugar alcohol metabolites decreased in patients with current or past infection, whereas fatty acid and lipid metabolites decreased only during current infection.

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.

Current understanding of heat shock response has been complicated by the fact that heat stress is inevitably accompanied by changes in specific growth rates and growth stages. In this study, a chemostat culture was successfully performed to avoid the physico-chemical and biological changes that accompany heatshock, which provided a unique opportunity to investigate the full range of cellular responses to thermal stress, ranging from temporary adjustment to phenotypic adaptation at multi-omics levels. Heat-responsive and time-resolved changes in the transcriptome and metabolome of a widely used E. coli strain BL21(DE3) were explored in which the temperature was upshifted from 37 to 42 °C. Omics profiles were categorized into early (2 and 10 min), middle (0.5, 1, and 2 h), and late (4, 8, and 40 h) stages of heat stress, each of which reflected the initiation, adaptation, and phenotypic plasticity steps of the stress response. The continued heat stress modulated global gene expression by controlling the expression levels of sigma factors in different time frames, including unexpected downregulation of the second heatshock sigma factor gene (rpoE) upon the heat stress. Trehalose, cadaverine, and enterobactin showed increased production to deal with the heat-induced oxidative stress. Genes highly expressed at the late stage were experimentally validated to provide thermotolerance. Intriguingly, a cryptic capsular gene cluster showed considerably high expression level only at the late stage, and its expression was essential for cell growth at high temperature. Granule-forming and elongated cells were observed at the late stage, which was morphological plasticity occurred as a result of acclimation to the continued heat stress. Whole process of thermal adaptation along with the genetic and metabolic changes at fine temporal resolution will contribute to far-reaching comprehension of the heat shock response. Further, the identified thermotolerant genes will be useful to rationally engineer thermotolerant microorganisms.

Although many studies have been conducted on leukemia, only a few have analyzed the metabolomic profiles of various leukemic cells. In this study, the metabolomes of THP-1, U937, KG-1 (acute myelogenous leukemia, AML), K562 (chronic myelogenous leukemia, CML), and cord blood-derived CD34-positive hematopoietic stem cells (HSC) were analyzed using gas chromatography-mass spectrometry, and specific metabolic alterations were found using multivariate statistical analysis. Compared to HSCs, leukemia cell metabolomes were found to have significant alterations, among which three were related to amino acids, three to sugars, and five to fatty acids. Compared to CML, four metabolomes were observed specifically in AML. Given that overall more metabolites are present in leukemia cells than in HSCs, we observed that the activation of glycolysis and oxidative phosphorylation (OXPHOS) metabolism facilitated the incidence of leukemia and the proliferation of leukemic cells. Analysis of metabolome profiles specifically present in HSCs and leukemia cells greatly increases our basic understanding of cellular metabolic characteristics, which is valuable fundamental knowledge for developing novel anticancer drugs targeting leukemia metabolism.