PubMed

Nature. 2023 Apr 26. doi: 10.1038/s41586-023-06017-4. Online ahead of print.ABSTRACTInflammation is a complex physiological process triggered in response to harmful stimuli1. It involves cells of the immune system capable of clearing sources of injury and damaged tissues. Excessive inflammation can occur as a result of infection and is a hallmark of several diseases2-4. The molecular bases underlying inflammatory responses are not fully understood. Here we show that the cell surface glycoprotein CD44, which marks the acquisition of distinct cell phenotypes in the context of development, immunity and cancer progression, mediates the uptake of metals including copper. We identify a pool of chemically reactive copper(II) in mitochondria of inflammatory macrophages that catalyses NAD(H) redox cycling by activating hydrogen peroxide. Maintenance of NAD+ enables metabolic and epigenetic programming towards the inflammatory state. Targeting mitochondrial copper(II) with supformin (LCC-12), a rationally designed dimer of metformin, induces a reduction of the NAD(H) pool, leading to metabolic and epigenetic states that oppose macrophage activation. LCC-12 interferes with cell plasticity in other settings and reduces inflammation in mouse models of bacterial and viral infections. Our work highlights the central role of copper as a regulator of cell plasticity and unveils a therapeutic strategy based on metabolic reprogramming and the control of epigenetic cell states.PMID:37100912 | DOI:10.1038/s41586-023-06017-4

Sci Rep. 2023 Apr 26;13(1):6828. doi: 10.1038/s41598-023-34132-9.ABSTRACTDietary restriction (DR) has been a very important discovery in modern aging biology research. Its remarkable anti-aging effect has been proved in a variety of organisms, including members of Lepidoptera, but mechanisms by which DR increases longevity are not fully understood. By using the silkworm (Bombyx mori), a model of lepidopteran insect, we established a DR model, isolated hemolymph from fifth instar larvae and employed LC-MS/MS metabolomics to analyze the effect of DR on the endogenous metabolites of silkworm, and tried to clarify the mechanism of DR to prolong lifespan. We identified the potential biomarkers by analyzing the metabolites of the DR and control groups. Then, we constructed relevant metabolic pathways and networks with MetaboAnalyst. DR significantly prolonged the lifespan of silkworm. The differential metabolites between the DR and control groups were mainly organic acids (including amino acid), and amines. These metabolites are involved in metabolic pathways such as amino acid metabolism. Further analysis showed that, the levels of 17 amino acids were significantly changed in the DR group, indicating that the prolonged lifespan was mainly due to changes in amino acid metabolism. Furthermore, we identified 41 and 28 unique differential metabolites in males and females, respectively, demonstrating sex differences in biological responses to DR. The DR group showed higher antioxidant capacity and lower lipid peroxidation and inflammatory precursors, with differences between the sexes. These results provide evidence for various DR anti-aging mechanisms at the metabolic level and novel reference for the future development of DR-simulating drugs or foods.PMID:37100857 | DOI:10.1038/s41598-023-34132-9

Carcinogenesis. 2023 Apr 26:bgad024. doi: 10.1093/carcin/bgad024. Online ahead of print.ABSTRACTNonmelanoma skin cancer (NMSC) is the most common cancer in the world. Environmental exposure to carcinogens is one of the major causes of NMSC initiation and progression. In the current study, we utilized a two-stage skin carcinogenesis mouse model generated by sequential exposure to cancer-initiating agent benzo[a]pyrene (BaP) and promoting agent 12-O-tetra-decanoylphorbol-13-acetate (TPA), to study epigenetic, transcriptomic, and metabolic changes at different stages during the development of NMSC. BaP caused significant alterations in DNA methylation and gene expression profiles in skin carcinogenesis, as evidenced by DNA-seq and RNA-seq analysis. Correlation analysis between differentially expressed genes and differentially methylated regions found that the mRNA expression of oncogenes leucine rich repeat LGI family member 2 (Lgi2), kallikrein related peptidase 13 (Klk13), and SRY-Box transcription factor (Sox5) are correlated with the promoter CpG methylation status, indicating BaP/TPA regulates these oncogenes through regulating their promoter methylation at different stages of NMSC. Pathway analysis identified that the modulation of macrophage-stimulating protein-recepteur d'origine nantais (MSP-RON) and high-mobility group box 1 (HMGB1) signaling pathways, superpathway of melatonin degradation, melatonin degradation 1, sirtuin signaling, and actin cytoskeleton signaling pathways are associated with the development of NMSC. The metabolomic study showed BaP/TPA regulated cancer-associated metabolisms like pyrimidine and amino acid metabolisms/metabolites and epigenetic-associated metabolites, such as S-adenosylmethionine, methionine, and 5-methylcytosine, indicating a critical role in carcinogen-mediated metabolic reprogramming and its consequences on cancer development. Altogether, this study provides novel insights integrating methylomic, transcriptomic, and metabolic signaling pathways that could benefit future skin cancer treatment and interception studies.PMID:37100755 | DOI:10.1093/carcin/bgad024

Vaccine. 2023 Apr 24:S0264-410X(23)00459-0. doi: 10.1016/j.vaccine.2023.04.045. Online ahead of print.ABSTRACTThe live attenuated temperature sensitive vaccine strain MS-H (Vaxsafe® MS, Bioproperties Pty. Ltd., Australia) is widely used to control disease associated with M. synoviae infection in commercial poultry. MS-H was derived from a field strain (86079/7NS) through N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-induced mutagenesis. Whole genomic sequence analysis of the MS-H and comparison with that of the 86079/7NS have found that MS-H contains 32 single nucleotide polymorphisms (SNPs). Three of these SNPs, found in the obgE, oppF and gapdh genes, have been shown to be prone to reversion under field condition, albeit at a low frequency. Three MS-H reisolates containing the 86079/7NS genotype in obgE (AS2), obgE and oppF (AB1), and obgE, oppF and gapdh (TS4), appeared to be more immunogenic and transmissible compared to MS-H in chickens. To investigate the influence of these reversions in the in vitro fitness of M. synoviae, the growth kinetics and steady state metabolite profiles of the MS-H reisolates, AS2, AB1 and TS4, were compared to those of the vaccine strain. Steady state metabolite profiling of the reisolates showed that changes in ObgE did not significantly influence the metabolism, while changes in OppF was associated with significant alterations in uptake of peptides and/or amino acids into the M. synoviae cell. It was also found that GAPDH plays a role in metabolism of the glycerophospholipids as well as an arginine deiminase (ADI) pathway. This study underscores the role of ObgE, OppF and GAPDH in M. synoviae metabolism, and suggests that the impaired fitness arising from variations in ObgE, OppF and GAPDH contributes to attenuation of MS-H.PMID:37100722 | DOI:10.1016/j.vaccine.2023.04.045

Tree Physiol. 2023 Apr 26:tpad046. doi: 10.1093/treephys/tpad046. Online ahead of print.ABSTRACTMichelia compressa (Maxim.) Sarg. is one of the important timber trees in Taiwan province, P. R. China. Michelia 'Zhongshanhanxiao' is a group of variants found among the progeny of M. compressa that exhibit higher growth rates compared with normal individuals, with significantly increased stem diameter and height, as well as enlarged leaves and flowers. However, the molecular mechanisms fostering the growth advantage and morphological variations are unknown and deserve further study. Through analyzing the transcriptome, metabolome and physiological processes of leaves, we identified remarkable differences in gene expression and metabolic profiles between Michelia 'Zhongshanhanxiao' and both the maternal M. compressa and its normal progeny. These differences were widely associated with plant-pathogen interaction, phenylpropanoid biosynthesis, cyanoamino acid metabolism, carbon fixation in photosynthetic organisms and plant hormone signal transduction. Additionally, physiological measurements showed that Michelia 'Zhongshanhanxiao' possesses stronger photosynthetic capacity and higher plant hormone contents. These results suggest that the heterosis of Michelia 'Zhongshanhanxiao' is regulated by candidates related to cell division, resistance to pathogens and accumulation of organic compounds. The findings of this study provide crucial information on the molecular mechanisms underlying the growth advantages conferred by heterosis in trees.PMID:37099801 | DOI:10.1093/treephys/tpad046

Plant Physiol. 2023 Apr 26:kiad236. doi: 10.1093/plphys/kiad236. Online ahead of print.ABSTRACTGlandular trichomes (GTs) are outgrowths of plant epidermal cells that secrete and store specialized secondary metabolites that protect plants against biotic and abiotic stresses and have economic importance for human use. While extensive work has been done to understand the molecular mechanisms of trichome organogenesis in Arabidopsis (Arabidopsis thaliana), which forms unicellular, non-glandular trichomes (NGTs), little is known about the mechanisms of GT development or regulation of secondary metabolites in plants with multicellular GTs. Here, we identified and functionally characterized genes associated with GT organogenesis and secondary metabolism in GTs of cucumber (Cucumis sativus). We developed a method for effective separation and isolation of cucumber GTs and NGTs. Transcriptomic and metabolomic analyses showed that flavonoid accumulation in cucumber GTs is positively associated with increased expression of related biosynthesis genes. We identified 67 GT development-related genes, the functions of 7 of which were validated by virus-induced gene silencing. We further validated the role of cucumber ECERIFERUM1 (CsCER1) in GT organogenesis by overexpression and RNA interference transgenic approaches. We further show that the transcription factor TINY BRANCHED HAIR (CsTBH) serves as a central regulator of flavonoid biosynthesis in cucumber glandular trichomes. Work from this study provides insight into the development of secondary metabolite biosynthesis in multi-cellular glandular trichomes.PMID:37099480 | DOI:10.1093/plphys/kiad236

J Chem Ecol. 2023 Apr 26. doi: 10.1007/s10886-023-01425-2. Online ahead of print.ABSTRACTThe metabolome represents an important functional trait likely important to plant invasion success, but we have a limited understanding of whether the entire metabolome or targeted groups of compounds confer an advantage to invasive as compared to native taxa. We conducted a lipidomic and metabolomic analysis of the cosmopolitan wetland grass Phragmites australis. We classified features into metabolic pathways, subclasses, and classes. Subsequently, we used Random Forests to identify informative features to differentiate five phylogeographic and ecologically distinct lineages: European native, North American invasive, North American native, Gulf, and Delta. We found that lineages had unique phytochemical fingerprints, although there was overlap between the North American invasive and North American native lineages. Furthermore, we found that divergence in phytochemical diversity was driven by compound evenness rather than metabolite richness. Interestingly, the North American invasive lineage had greater chemical evenness than the Delta and Gulf lineages but lower evenness than the North American native lineage. Our results suggest that metabolomic evenness may represent a critical functional trait within a plant species. Its role in invasion success, resistance to herbivory, and large-scale die-off events common to this and other plant species remain to be investigated.PMID:37099216 | DOI:10.1007/s10886-023-01425-2

Metabolomics. 2023 Apr 26;19(5):46. doi: 10.1007/s11306-023-02005-x.ABSTRACTINTRODUCTION: Uzbekistan is one of the countries with the highest number of diet-related chronic diseases, which is believed to be associated with high animal fat intake. Sheep meat is high in fats (~ 5% in muscle), including saturated and monounsaturated fatty acids, and it contains nearly twice the higher amounts of n-3 polyunsaturated fatty acids and conjugated linoleic acids compared to beef. Nevertheless, sheep meat is considered health promoting by the locals in Uzbekistan and it accounts for around 1/3 of red meat intake in the country.OBJECTIVES: The aim of this study was to apply a metabolomics approach to investigate if sheep meat intake frequency (SMIF) is associated with alterations in fasting blood plasma metabolites and lipoproteins in healthy Uzbek adults.METHODS: The study included 263 subjects, 149 females and 114 males. For each subject a food intake questionnaire, including SMIF, was recorded and fasting blood plasma samples were collected for metabolomics. Blood plasma metabolites and lipoprotein concentrations were determined using 1H NMR spectroscopy.RESULTS AND CONCLUSION: The results showed that SMIF was confounded by nationality, sex, body mass index (BMI), age, intake frequency of total meat and fish in ascending order (p < 0.01). Multivariate and univariate data analyses showed differences in the levels of plasma metabolites and lipoproteins with respect to SMIF. The effect of SMIF after statistical adjustment by nationality, sex, BMI, age, intake frequency of total meat and fish decreased but remained significant. Pyruvic acid, phenylalanine, ornithine, and acetic acid remained significantly lower in the high SMIF group, whereas choline, asparagine, and dimethylglycine showed an increasing trend. Levels of cholesterol, apolipoprotein A1, as well as low- and high-density lipoprotein subfractions all displayed a decreasing trend with increased SMIF although the difference were not significant after FDR correction.PMID:37099187 | DOI:10.1007/s11306-023-02005-x

Appl Microbiol Biotechnol. 2023 Apr 26. doi: 10.1007/s00253-023-12535-y. Online ahead of print.ABSTRACTAlfalfa silage fermentation quality, metabolome, bacterial interactions, and successions as well as their predicted metabolic pathways were explored under different dry matter contents (DM) and lactic acid bacteria (LAB) inoculations. Silages were prepared from alfalfa with DM contents of 304 (LDM) and 433 (HDM) g/kg fresh weight and inoculated with Lactiplantibacillus plantarum (L. plantarum, LP), Pediococcus pentosaceus (P. pentosaceus, PP), or sterile water (control). The silages were stored at a simulated hot climate condition (35°C) and sampled at 0, 7, 14, 30, and 60 days of fermentation. The results revealed that HDM significantly improved the alfalfa silage quality and altered microbial community composition. The GC-TOF-MS analysis discovered 200 metabolites in both LDM and HDM alfalfa silage, mainly consisting of amino acids, carbohydrates, fatty acids, and alcohols. Compared with LP and control, PP-inoculated silages had increased concentrations of lactic acid (P < 0.05) and essential amino acids (threonine and tryptophan) as well as decreased pH, putrescine content, and amino acid metabolism. However, alfalfa silage inoculated with LP had higher proteolytic activities than control and PP-inoculated silage, as revealed by a higher concentration of ammonia nitrogen (NH3-N), and also upregulated amino acid and energy metabolism. HDM content and P. pentosaceus inoculation significantly altered the composition of alfalfa silage microbiota from 7 to 60 days of ensiling. Conclusively, these results indicated that inoculation with PP exhibited great potential in enhancing the fermentation of silage with LDM and HDM via altering the microbiome and metabolome of the ensiled alfalfa, which could help in understanding and improving the ensiling practices under hot climate conditions. KEY POINTS: • HDM improved fermentation quality and declined putrescine content of alfalfa silage • P. pentosaceus inoculation enhanced the fermentation quality of alfalfa silage • P. pentosaceus is an ideal inoculant for alfalfa silage under high temperature.PMID:37099058 | DOI:10.1007/s00253-023-12535-y

Stem Cell Rev Rep. 2023 Apr 26. doi: 10.1007/s12015-023-10541-1. Online ahead of print.ABSTRACTIntracerebral hemorrhage (ICH) is a severe subtype of stroke for which there is no effective treatment. Stem cell and exosome (Exo) therapies have great potential as new approaches for neuroprotection and neurorestoration in treating ICH. We aimed to investigate whether Exo affects ICH by regulating the ecology of gut microbiota and metabolism and the mechanisms involved. First, differential miRNAs in ICH were screened by bioinformatics and verified by qRT-PCR. Then, Exo was extracted from mouse bone marrow mesenchymal stem cells (MSCs) and identified. Dual-luciferase reporter gene assay was utilized to verify the binding relationship between miR-150-3p and TRAF6. A mouse ICH model was constructed and treated with Exo. Next, we knocked down miR-150-3p and performed fecal microbiota transplantation (FMT). Then changes in gut microbiota and differential metabolites were detected by 16S rRNA sequencing and metabolomics analysis. We found that miR-150-3p expression was lowest in the brain tissue of the ICH group compared to the Sham group. Besides, low miR-150-3p level in ICH was encapsulated by MSC-derived Exo. Moreover, miR-150-3p bound to TRAF6 and was negatively correlated. With the addition of ExomiR-150-3p inhibitor, we found that MSC-derived exosomal miR-150-3p may affect ICH injury via TRAF6/NLRP3 axis. MSC-derived exosomal miR-150-3p caused changes in gut microbiota, including Proteobacteria, Muribaculaceae, Lachnospiraceae_NK4A136_group, and Acinetobacter. Moreover, MSC-derived exosomal miR-150-3p caused changes in metabolism. After further FMT, gut microbiota-mediated MSC-derived Exo affected ICH with reduced apoptosis and reduced levels of inflammatory factors. In conclusion, MSC-derived exosomal miR-150-3p affected ICH by regulating TRAF6/NF-κB axis, gut microbiota and metabolism.PMID:37099039 | DOI:10.1007/s12015-023-10541-1

J Sci Food Agric. 2023 Apr 26. doi: 10.1002/jsfa.12665. Online ahead of print.ABSTRACTBACKGROUND: Bifidobacterium pseudolongum is widely exists in mammal gut and its abundance is associated with human and animal health. The purpose of this study was to investigate the potential mechanisms of B. pseudolongum CCFM1253 on protecting against lipopolysaccharide (LPS)-induced acute liver injury (ALI) by metagenomic analysis and liver metabolomic profiles.RESULTS: B. pseudolongum CCFM1253 preintervention remarkably attenuated the influence of LPS on serum alanine transaminase (ALT) and aspartate amino transferase (AST) activities. B. pseudolongum CCFM1253 preintervention remarkably attenuated the inflammation responses [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] and elevated antioxidative enzymes activities [total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px)] in ALI mice by intervening the Nf-kβ and Nrf2 pathways, respectively. B. pseudolongum CCFM1253 treatment elevated the proportion of Alistipes and Bifidobacterium, and decreased the proportion of uncultured Bacteroidales bacterium, Muribaculum, Parasutterella, Ruminococcaceae UCG-010 in ALI mice, which were strongly correlated with the inhibition of inflammation responses and oxidative stress. Untargeted liver metabolomics exhibited that the hepatoprotective efficacy of B. pseudolongum CCFM1253 might be achieved by altering liver metabolites-related riboflavin metabolism, phenylalanine metabolism, alanine, citrate cycle (TCA cycle), and so on. Furthermore, riboflavin exposure could control the contents of MDA, SOD, and CAT in hydrogen peroxide-treated HepG2 cells.CONCLUSION: B. pseudolongum CCFM1253 can effectively alleviate inflammatory response and oxidative stress, and regulate the intestinal microbiota composition and liver metabolism, and elevate the liver riboflavin content in LPS-treated mice. Therefore, B. pseudolongum CCFM1253 could serves as a potential probiotic to ameliorate the host health. This article is protected by copyright. All rights reserved.PMID:37099000 | DOI:10.1002/jsfa.12665

Biotechnol Genet Eng Rev. 2023 Apr 26:1-27. doi: 10.1080/02648725.2023.2204715. Online ahead of print.ABSTRACTHyperuricemia (HUA) is a common complication of chronic kidney disease (CKD). Conversely, HUA can promote the disease progression of CKD. However, the molecular mechanism of HUA in CKD development remains unclear. In the present study, we applied ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze the serum metabolite profiling of 47 HUA patients, 41 non-hyperuricemic CKD (NUA-CKD) patients, and 51 CKD and HUA (HUA-CKD) patients, and then subjected to multivariate statistical analysis, metabolic pathway analysis and diagnostic performance evaluation. Metabolic profiling of serums showed that 40 differential metabolites (fold-change threshold (FC) > 1.5 or<2/3, variable importance in projection (VIP) > 1, and p < 0.05) were screened in HUA-CKD and HUA patients, and 24 differential metabolites (FC > 1.2 or<0.83, VIP>1, and p < 0.05) were screened in HUA-CKD and NUA-CKD patients. According to the analysis of metabolic pathways, significant changes existed in three metabolic pathways (compared with the HUA group) and two metabolic pathways (compared with the HUA-CKD group) in HUA-CKD patients. Glycerophospholipid metabolism was a significant pathway in HUA-CKD. Our findings show that the metabolic disorder in HUA-CKD patients was more serious than that in NUA-CKD or HUA patients. A theoretical basis is provided for HUA to accelerate CKD progress.PMID:37098873 | DOI:10.1080/02648725.2023.2204715

Food Funct. 2023 Apr 26. doi: 10.1039/d2fo03493j. Online ahead of print.ABSTRACTAkkermansia muciniphila (A. muciniphila) plays an important role in intestinal regulation, while it is presently unclear whether live or pasteurized A. muciniphila has different effects on the intestinal health. In the present study, live or pasteurized A. muciniphila was administered to dextran sulfate sodium (DSS)-induced ulcerative colitis mice to investigate its influences on the host intestinal health, gut microbiota, and metabolomic phenotype. The results showed that pasteurized A. muciniphila alleviated the symptoms of colitis in mice more efficiently by encouraging the proliferation of beneficial intestinal bacteria, increasing the production of short-chain fatty acids, and inhibiting intestinal inflammation. Moreover, pasteurized A. muciniphila increased the abundance of Parasutterella and Akkermansia and thus affected the metabolism of lipid and lipid-like molecules associated with lysophosphatidylcholines (LysoPCs). Notably, prophylactic supplementation of pasteurized A. muciniphila increased the relative abundance of the anti-inflammatory microbe Dubosiella, thereby activating intestinal sphingolipid metabolism to alleviate intestinal damage. In conclusion, pasteurized A. muciniphila showed a more effective amelioration of DSS-induced colitis by repairing the dysbiosis of gut microbiota and intestinal metabolism compared to live A. muciniphila, providing a potential strategy to explore the protective effect of A. muciniphila on host intestinal health.PMID:37098829 | DOI:10.1039/d2fo03493j

Chem Commun (Camb). 2023 Apr 26. doi: 10.1039/d3cc01223a. Online ahead of print.ABSTRACTThe microbiome has been identified to have a key role for the physiology of their human host. One of the major impacts is the clearance of bacterial pathogens. We have now developed a chemoselective probe methodology for the absolute quantification of short-chain fatty acids at low nM concentrations, with high reproducibility and spiked isotope labelled internal standards. Immobilization to magnetic beads allows for separation from the matrix and the tagged metabolites upon bioorthogonal cleavage can be analyzed via UHPLC-MS. The major advantage of our sensitive method is the simple combination with global metabolomics analysis as only a small sample volume is required. We have applied this chemical metabolomics strategy for targeted SCFA analysis combined with global metabolomics on gut microbiome co-cultures with Salmonella and investigated the effect of antibiotic treatment.PMID:37098752 | DOI:10.1039/d3cc01223a

Mol Omics. 2023 Apr 26. doi: 10.1039/d2mo00274d. Online ahead of print.ABSTRACTDespite some advances in the study of radiation injuries, effective methods of prevention and treatment of severe acute radiation syndrome or illness (ARS) are still lacking. Therefore, an in-depth understanding of the biological characteristics associated with high dose radiation is essential to reveal the mechanisms underlying the varied biological processes following high dose radiation and the development of novel potent radioprotective agents. In the present study, plasma metabolic characteristics were investigated using hematopoietic stem cell transplantation patients (n = 36) undergoing total body ionizing irradiation (TBI) utilizing gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Plasma was collected pre-irradiation, 3 days after completion of fractionated radiation therapy with a total dose of 12 Gy delivered at a dose rate of 8 cGy min-1. These metabolic disorders involve the dysregulation of the gut microflora, a shift in energy supply from aerobic respiration toward ketogenesis, protein synthesis and metabolism in response to TBI. Furthermore, the panel of four metabolic markers with most potential consisting of PC (O-38:5), urate, ornithine, and GCDCS for radiation injury was chosen by combining multiple methods of data processing that included univariate analysis, partial least squares discriminant analysis (PLS-DA), and multivariable stepwise linear regression analysis. While similar patterns of metabolic alterations were observed in patients of different genders, disease types and ages, specific changes were also found in specific patients following high doses of exposure. These findings provide valuable information for selecting metabolic biomarker panels for radiation injury, clues for radiation pathology and therapeutic interventions involved in high-dose radiation exposure.PMID:37098727 | DOI:10.1039/d2mo00274d

Biotechnol Biofuels Bioprod. 2023 Apr 25;16(1):70. doi: 10.1186/s13068-023-02321-3.ABSTRACTBACKGROUND: Soybean (Glycine max (L.) Merr) is an important source of human food, animal feed, and bio-energy. Although the genetic network of lipid metabolism is clear in Arabidopsis, the understanding of lipid metabolism in soybean is limited.RESULTS: In this study, 30 soybean varieties were subjected to transcriptome and metabolome analysis. In total, 98 lipid-related metabolites were identified, including glycerophospholipid, alpha-linolenic acid, linoleic acid, glycolysis, pyruvate, and the sphingolipid pathway. Of these, glycerophospholipid pathway metabolites accounted for the majority of total lipids. Combining the transcriptomic and metabolomic analyses, we found that 33 lipid-related metabolites and 83 lipid-related genes, 14 lipid-related metabolites and 17 lipid-related genes, and 12 lipid-related metabolites and 25 lipid-related genes were significantly correlated in FHO (five high-oil varieties) vs. FLO (five low-oil varieties), THO (10 high-oil varieties) vs. TLO (10 low-oil varieties), and HO (15 high-oil varieties) vs. LO (15 low-oil varieties), respectively.CONCLUSIONS: The GmGAPDH and GmGPAT genes were significantly correlated with lipid metabolism genes, and the result revealed the regulatory relationship between glycolysis and oil synthesis. These results improve our understanding of the regulatory mechanism of soybean seed oil improvement.PMID:37098528 | DOI:10.1186/s13068-023-02321-3

Food Microbiol. 2023 Aug;113:104273. doi: 10.1016/j.fm.2023.104273. Epub 2023 Apr 5.ABSTRACTSpoilage of juice and beverages by a thermo-acidophilic bacterium, Alicyclobacillus acidoterrestris, has been considered to be a major and widespread concern for juice industry. Acid-resistant property of A. acidoterrestris supports its survival and multiplication in acidic juice and challenges the development of corresponding control measures. In this study, intracellular amino acid differences caused by acid stress (pH 3.0, 1 h) were determined by targeted metabolomics. The effect of exogenous amino acids on acid resistance of A. acidoterrestris and the related mechanisms were also investigated. The results showed that acid stress affected the amino acid metabolism of A. acidoterrestris, and the selected glutamate, arginine, and lysine contributed to its survival under acid stress. Exogenous glutamate, arginine, and lysine significantly increased the intracellular pH and ATP level, alleviated cell membrane damage, reduced surface roughness, and suppressed deformation caused by acid stress. Additionally, the up-regulated gadA and speA genes and the enhanced enzymatic activity confirmed that glutamate and arginine decarboxylase systems played a crucial role in maintaining pH homeostasis of A. acidoterrestris under acid stress. Our research reveals an important factor contributing to acid resistance of A. acidoterrestris, which provides an alternative target for effectively controlling this contaminant in fruit juices.PMID:37098432 | DOI:10.1016/j.fm.2023.104273

Food Microbiol. 2023 Aug;113:104281. doi: 10.1016/j.fm.2023.104281. Epub 2023 Apr 5.ABSTRACTArginine deiminase pathway, controlled by arginine deiminase, ornithine carbamoyltransferase and carbamate kinase, could affect and modulate the intracellular pH homeostasis of lactic acid bacteria under acid stress. Herein, strategy based on exogenous addition of arginine had been proposed to improve the robustness of Tetragenococcus halophilus during acid stressed condition. Results indicated cells cultured in the presence of arginine acquired high tolerance to acid stress mainly through maintaining the homeostasis of intracellular microenvironment. Additionally, metabolomic analysis and q-PCR showed the content of intracellular metabolites and expression levels of genes involved in ADI pathway significantly increased when cells encountered acid stress with the presence of exogenous arginine. Furthermore, Lactococcus lactis NZ9000 with heterologous overexpression of arcA and arcC from T. halophilus exhibited high stress tolerance to acidic condition. This study may provide an insight into the systematical understanding about the mechanism underlying acid tolerance and improve the fermentation performance of LAB during harsh condition.PMID:37098426 | DOI:10.1016/j.fm.2023.104281

Cell Host Microbe. 2023 Apr 18:S1931-3128(23)00147-6. doi: 10.1016/j.chom.2023.04.003. Online ahead of print.ABSTRACTClostridioides difficile infections (CDIs) remain a healthcare problem due to high rates of relapsing/recurrent CDIs (rCDIs). Breakdown of colonization resistance promoted by broad-spectrum antibiotics and the persistence of spores contribute to rCDI. Here, we demonstrate antimicrobial activity of the natural product class of chlorotonils against C. difficile. In contrast to vancomycin, chlorotonil A (ChA) efficiently inhibits disease and prevents rCDI in mice. Notably, ChA affects the murine and porcine microbiota to a lesser extent than vancomycin, largely preserving microbiota composition and minimally impacting the intestinal metabolome. Correspondingly, ChA treatment does not break colonization resistance against C. difficile and is linked to faster recovery of the microbiota after CDI. Additionally, ChA accumulates in the spore and inhibits outgrowth of C. difficile spores, thus potentially contributing to lower rates of rCDI. We conclude that chlorotonils have unique antimicrobial properties targeting critical steps in the infection cycle of C. difficile.PMID:37098342 | DOI:10.1016/j.chom.2023.04.003

Food Chem. 2023 Apr 1;420:136050. doi: 10.1016/j.foodchem.2023.136050. Online ahead of print.ABSTRACTThe aim of the present study was to comparatively investigate the relative phytochemical profiles (phenolic content, organic and amino acids, free sugars, and other metabolites using metabolomics approach), and bioactive potentials of young (YS) and mature soybean (MS) upon in vitro simulated gastrointestinal digestion (SGID). Cumulatively, a total of 198 metabolites were identified in MS and YS, 119 metabolites in undigested YS, and a total of 136 metabolites in undigested MS, which further increased to 156 and 152 in YS and MS upon SGID, respectively. Gastric digesta of both YS and MS exhibited higher inhibitory properties towards α-amylase and DPP-IV enzymes than their intestinal digesta. Furthermore, the intestinal digesta of MS showed higher antioxidant and anti-inflammatory activities compared to the YS intestinal digesta. Overall, the results suggested that the gastrointestinal digestion of YS and MS displayed distinctive metabolic profiles together with varied bioactive potentials.PMID:37098305 | DOI:10.1016/j.foodchem.2023.136050