PubMed

Anal Chem. 2023 Mar 27. doi: 10.1021/acs.analchem.2c04887. Online ahead of print.ABSTRACTInconsistent peak picking outcomes are a critical concern in processing liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics data. This work systematically studied the mechanisms behind the discrepancies among five commonly used peak picking algorithms, including CentWave in XCMS, linear-weighted moving average in MS-DIAL, automated data analysis pipeline (ADAP) in MZmine 2, Savitzky-Golay in El-MAVEN, and FeatureFinderMetabo in OpenMS. We first collected 10 public metabolomics datasets representing various LC-MS analytical conditions. We then incorporated several novel strategies to (i) acquire the optimal peak picking parameters of each algorithm for a fair comparison, (ii) automatically recognize false metabolic features with poor chromatographic peak shapes, and (iii) evaluate the real metabolic features that are missed by the algorithms. By applying these strategies, we compared the true, false, and undetected metabolic features in each data processing outcome. Our results show that linear-weighted moving average consistently outperforms the other peak picking algorithms. To facilitate a mechanistic understanding of the differences, we proposed six peak attributes: ideal slope, sharpness, peak height, mass deviation, peak width, and scan number. We also developed an R program to automatically measure these attributes for detected and undetected true metabolic features. From the results of the 10 datasets, we concluded that four peak attributes, including ideal slope, scan number, peak width, and mass deviation, are critical for the detectability of a peak. For instance, the focus on ideal slope critically hinders the extraction of true metabolic features with low ideal slope scores in linear-weighted moving average, Savitzky-Golay, and ADAP. The relationships between peak picking algorithms and peak attributes were also visualized in a principal component analysis biplot. Overall, the clear comparison and explanation of the differences between peak picking algorithms can lead to the design of better peak picking strategies in the future.PMID:36972195 | DOI:10.1021/acs.analchem.2c04887

Metabolomics. 2023 Mar 27;19(4):23. doi: 10.1007/s11306-023-01993-0.ABSTRACTINTRODUCTION: The white asparagus season lasts 4 months while the harvest period per field is 8 weeks. Different varieties are better suited for harvesting early or late in the season. Little is known of the dynamics of secondary metabolites of white asparagus during the production season.OBJECTIVE: Characterization of the metabolome of white asparagus spears covering volatile and non-volatile composition in relation to quality aspects.METHODS: Eight varieties, harvested repeatedly during two consecutive seasons were analysed following an untargeted metabolomics workflow using SPME GC-MS and LC-MS. Linear regression, cluster and network analyses were used to explore the profile dynamics, unravel patterns and study the influence of genotype and environment.RESULTS: The metabolite profiles were influenced by the harvest moment and genetic background. Metabolites that significantly changed over time were distributed across seven clusters based on their temporal patterns. Two clusters including monoterpenes, benzenoids and saponins showed the most prominent seasonal changes. The changes depicted by the other five clusters were mainly ≤ 2-fold relative to the harvest start. Known asparagus aroma compounds were found to be relatively stable across the season/varieties. Heat-enhanced cultivation appeared to yield spears early in season with a similar metabolome to those harvested later.CONCLUSION: The dynamics of the white asparagus metabolome is influenced by a complex relationship between the onset of spear development, the moment of harvest and the genetic background. The typical perceived asparagus flavour profile is unlikely to be significantly affected by these dynamics.PMID:36971968 | DOI:10.1007/s11306-023-01993-0

Adv Exp Med Biol. 2023 Mar 28. doi: 10.1007/5584_2023_770. Online ahead of print.ABSTRACTStudies analyzing the relationship between microbiota composition and the thyroid have been increasing rapidly in recent years, and evidence has recently come to light about the involvement of the gut microbiota in various aspects of thyroid pathology. Recently, besides studies analyzing the microbiota composition of different biological niches (salivary microbiota or thyroid tumor microenvironment) in patients with thyroid disorders, some studies have been carried out in peculiar subcategories of patients (pregnant women or obese). Other studies added a metabolomic insight into the characterization of fecal microflora in an attempt to enlighten specific metabolic pathways that could be involved in thyroid disorder pathogenesis. Lastly, some studies described the use of probiotics or symbiotic supplementation aimed at modulating gut microbiota composition for therapeutic purposes. The aim of this systematic review is to analyze the last advancements in the relationship between gut microbiota composition and thyroid autoimmunity, extending the analysis also to nonautoimmune thyroid disorders as well as to the characterization of the microbiota belonging to different biological niches in these patients. The overall results of the present review article strengthen the existence of a bidirectional relationship between the intestine, with its microbial set, and thyroid homeostasis, thus supporting the newly recognized entity known as the gut-thyroid axis.PMID:36971966 | DOI:10.1007/5584_2023_770

Metabolomics. 2023 Mar 27;19(4):24. doi: 10.1007/s11306-023-01983-2.ABSTRACTINTRODUCTION AND OBJECTIVE: Taking into consideration the challenges of lipid analytics, present study aims to design the best high-throughput workflow for detection and annotation of lipids.MATERIAL AND METHODS: Serum lipid profiling was performed on CSH-C18 and EVO-C18 columns using UHPLC Q-TOF-MS and generated lipid features were annotated based on m/z and fragment ion using different software.RESULT AND DISCUSSION: Better detection of features was observed in CSH-C18 than EVO-C18 with enhanced resolution except for Glycerolipids (triacylglycerols) and Sphingolipids (sphingomyelin).CONCLUSION: The study revealed an optimized untargeted Lipidomics-workflow with comprehensive lipid profiling (CSH-C18 column) and confirmatory annotation (LipidBlast).PMID:36971892 | DOI:10.1007/s11306-023-01983-2

Am J Hematol. 2023 Mar 27. doi: 10.1002/ajh.26923. Online ahead of print.ABSTRACTDespite a wealth of exploratory plasma metabolomics studies in sickle cell disease (SCD), no study to date has evaluate a large and well phenotyped cohort to compare the primary erythrocyte metabolome of hemoglobin SS, SC and transfused AA red blood cells (RBCs) in vivo. The current study evaluates the RBC metabolome of 587 subjects with sickle cell sickle cell disease (SCD) from the WALK-PHaSST clinical cohort. The set includes hemoglobin SS, hemoglobin SC SCD patients, with variable levels of HbA related to RBC transfusion events. Here we explore the modulating effects of genotype, age, sex, severity of hemolysis, and transfusion therapy on sickle RBC metabolism. Results show that RBCs from patients with Hb SS genotypes - compared to AA RBCs from recent transfusion events or SC RBCs - are characterized by significant alterations of RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine and urate metabolism. Surprisingly, the RBC metabolism of SC RBCs is dramatically different from SS, with all glycolytic intermediates significantly elevated in SS RBCs, with the exception of pyruvate. This result suggests a metabolic blockade at the ATP-generating phosphoenolpyruvate to pyruvate step of glycolysis, which is catalyzed by redox-sensitive pyruvate kinase. Metabolomics, clinical and hematological data were collated in a novel online portal. In conclusion, we identified metabolic signatures of HbS RBCs that correlate with the degree of steady state hemolytic anemia, cardiovascular and renal dysfunction and mortality. This article is protected by copyright. All rights reserved.PMID:36971592 | DOI:10.1002/ajh.26923

J Sci Food Agric. 2023 Mar 27. doi: 10.1002/jsfa.12575. Online ahead of print.ABSTRACTBACKGROUND: Hempseeds (Cannabis sativa L.) are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber, which are of highly nutritional value. Probiotics have been found to relieve constipation, which solved a health problem that constantly troubles most people. Therefore, the changes in the metabolites of fermented yogurt with or without 10% defatted hempseed meal (10% SHY or 0% SHY) were studied and their laxative effects were performed through animal experiment.RESULTS: Amino acids and peptides, terpene glycosides, carbohydrates, lineolic acids, and fatty acids were found to be the major contributors to the discrimination of metabolic profile between 0% SHY and 10% SHY. The differentially accumulated metabolites may lead to the discrepancy on yogurts' functionality. Animal experiments showed that 10% SHY treatment prevented constipation by increasing fecal number, fecal water content and small intestinal transit rate, and reducing inflammatory injury in loperamide-induced constipation rats. Further analysis of the gut microbiota revealed that 10% SHY gavage increased the relative abundances of the genera Lactobacillus, Allobaculum, Turicibacter, Oscillibacter, Ruminococcus, and Phascolarctobacterium in the constipated rats, whereas decreased that of Akkermansia, Clostridium_XlVa, Bacteroides, Staphylococcus, and Clostridium_lV. The combination of defatted hempseed meal and probiotics was found to be effective in relieving constipation, probably due to the enriched amino acids and peptides, such as Thr-Leu and lysinoalanine through correlation analysis.CONCLUSION: Our findings indicated that defatted hempseed meal in yogurt altered the metabolic profile and effectively alleviated constipation in rats, which is a promising therapeutic candidate for constipation. This article is protected by copyright. All rights reserved.PMID:36971462 | DOI:10.1002/jsfa.12575

J Agric Food Chem. 2023 Mar 27. doi: 10.1021/acs.jafc.2c07163. Online ahead of print.ABSTRACTDrought adaptation of plants is closely related to resistance and tolerance to drought stress as well as the ability to recover after the elimination of the stress. Glycyrrhiza uralensis Fisch is a commonly applied herb whose growth and development are greatly affected by drought. Here, we provide the first comprehensive analysis of the transcriptomic, epigenetic, and metabolic responses of G. uralensis to drought stress and rewatering. The hyper-/hypomethylation of genes may lead to up-/downregulated gene expression, and epigenetic changes can be regarded as an important regulatory mechanism of G. uralensis under drought stress and rewatering. Moreover, integrated transcriptome and metabolome analysis revealed that genes and metabolites involved in pathways of antioxidation, osmoregulation, phenylpropanoid biosynthesis, and flavonoid biosynthesis may regulate the drought adaptation of G. uralensis. This work provides crucial insights into the drought adaptation of G. uralensis and offers epigenetic resources for cultivating G. uralensis with high drought adaptation.PMID:36971245 | DOI:10.1021/acs.jafc.2c07163

Biotechnol Genet Eng Rev. 2023 Mar 27:1-24. doi: 10.1080/02648725.2023.2195082. Online ahead of print.ABSTRACTSecondary lymphoedema is one of the common complications after lymph node dissection for gynecologic malignancies and breast cancer. In this study, the relationship between PLA2 and postoperative lymphoedema in cancer at the molecular level has been explored through transcriptomics and metabolomic assays. Transcriptome sequencing technology, as well as metabolomic assays, were utilized to explore the expression of PLA2 in lymphoedema patients, and search for potential pathways in the pathogenesis and exacerbation mechanism of lymphoedema. The effect of sPLA2 on human lymphatic endothelial cells was investigated by culturing human lymphatic endothelial cells. Secretory phospholipases A2 (sPLA2) showed high expression levels in lymphoedema tissues, however, cytoplasmic phospholipases A2 (cPLA2), showed low expression in lymphoedema, as demonstrated by RT-qPCR. By culturing human lymphatic vascular endothelial cells, the study found that sPLA2 causes HLEC vacuolization and has an inhibitory effect on HLEC proliferation and migration. By detecting sPLA2 in the serum of lymphoedema patients and analyzing clinical data, it was found that sPLA2 was positively correlated with the severity of lymphoedema. Secretory Phospholipase A2 (sPLA2) is highly expressed in lymphoedema tissue, damages lymphatic vessel endothelial cells, is strongly associated with disease severity, and can be used as a potential predictor of disease severity.Abbreviations: PLA2: Phospholipase A2; DEGs: differentially expressed genes; DMP: differential metabolic production.PMID:36971244 | DOI:10.1080/02648725.2023.2195082

J Agric Food Chem. 2023 Mar 27. doi: 10.1021/acs.jafc.2c08949. Online ahead of print.ABSTRACTZanthoxylum plants (ZPs), including multiple Chinese prickly ash species, are dual-purpose functional foods favored by the general population around the world in foods, cosmetics, and traditional medicines and have antipruritic, insecticidal, and fungicidal bioactivities. For the first time, the anti-roundworm bioactivity of ZPs and the active ingredients were compared and investigated. Through nontarget metabolomics following targeted quantitative analysis, qinbunamides, sanshools, sanshooel, asarinin, and sesamin were found to be the main different components of Zanthoxylum species. Coincidentally, the 12 chemical components were also the dominant anti-roundworm ingredients of ZP extracts. The extracts of three species of Chinese prickly ash (1 mg/mL) decreased the hatchability of roundworm eggs significantly, and the ChuanJiao seed killed roundworms (insecticidal rate 100%) and alleviated the symptoms of pneumonia in mice. Furthermore, retention time-accurate mass-tandem mass spectrometry-ion ratio (RT-AM-MS/MS-IR) were modeled by assaying 108 authentic compounds of ZP extracts, and 20 metabolites were confidently identified in biological samples from ZP extract-treated mice by analyzing the m/z values and the empirical substructures. This study provides a good reference for the proper application of ZPs.PMID:36971186 | DOI:10.1021/acs.jafc.2c08949

Neuro Oncol. 2023 Mar 27:noad064. doi: 10.1093/neuonc/noad064. Online ahead of print.ABSTRACTBACKGROUND: Pediatric high-grade glioma (pHGG) is largely incurable and accounts for most brain tumor-related deaths in children. Radiation is a standard therapy, yet the benefit from this treatment modality is transient, and most children succumb to disease within 2 years. Recent large-scale genomic studies suggest that pHGG have alterations in DNA damage response (DDR) pathways that induce resistance to DNA damaging agents. The aim of this study was to evaluate the therapeutic potential and molecular consequences of combining radiation with selective DDR inhibition in pHGG.METHODS: We conducted an unbiased screen in pHGG cells that combined radiation with clinical candidates targeting the DDR and identified the ATM inhibitor AZD1390. Subsequently, we profiled AZD1390 + radiation in an extensive panel of early passage pHGG cell lines, mechanistically characterized response to the combination in vitro in sensitive and resistant cells and evaluated the combination in vivo using TP53 wild-type and TP53 mutant orthotopic xenografts.RESULTS: AZD1390 significantly potentiated radiation across molecular subgroups of pHGG by increasing mutagenic non-homologous end joining and augmenting genomic instability. In contrast to previous reports, ATM inhibition significantly improved the efficacy of radiation in both TP53 wild-type and TP53 mutant isogenic cell lines and distinct orthotopic xenograft models. Furthermore, we identified a novel mechanism of resistance to AZD1390 + radiation that was marked by an attenuated ATM pathway response which dampened sensitivity to ATM inhibition and induced synthetic lethality with ATR inhibition.CONCLUSIONS: Our study supports the clinical evaluation of AZD1390 in combination with radiation in pediatric patients with HGG.PMID:36971093 | DOI:10.1093/neuonc/noad064

Transfusion. 2023 Mar 27. doi: 10.1111/trf.17332. Online ahead of print.ABSTRACTBACKGROUND: Exposure to radiation through battlefield use of nuclear weapons, terrorist attacks or accidents at nuclear power plants is a current concern for the military. Beyond the risk of exposure to personnel is the intentional or accidental irradiation of our blood banking supply system. It is unknown how large doses of ionizing radiation affect storage of blood and blood products, including platelets. The major function of platelets is clot formation which includes aggregation, shape change, vesicle release, and fibrinogen attachment; these tasks require a significant amount of energy. Here we determine if ionizing radiation effects the energy metabolome of platelets in storage.STUDY DESIGN AND METHODS: Fresh whole blood from healthy volunteers was subjected to 0, 25 or 75Gy of X-irradiation, and stored at 4°C. Platelets were isolated from stored WB at 0, 1, 7, 14 and 21 days of storage. Krebs cycle intermediates, nicotinamide adenine dinucleotides, and the tri-, di and mono- phosphorylated versions of adenosine and guanosine were extracted and measured by tandem mass spectroscopy.RESULTS: Irradiation at either 25Gy or 75Gy had no significant effect on the amount of any metabolite measured compared to control (0Gy). However, there was a significant fall over time in storage for most of the metabolites measured.DISCUSSION: These data show that irradiation at high doses has no effect on the concentration of the energy metabolome of platelets derived from whole blood stored in 4°C for up to 21 days and suggests that platelets can maintain their metabolome even after radiation exposure. This article is protected by copyright. All rights reserved.PMID:36971034 | DOI:10.1111/trf.17332

Benef Microbes. 2023 Mar 27:1-12. doi: 10.3920/BM2022.0053. Online ahead of print.ABSTRACTIntestinal microbiota correction in the therapy of irritable bowel syndrome (IBS) is an important medical problem. We conducted a laboratory and pilot clinical trial to investigate the effect of autoprobiotic bacteria, indigenous bifidobacteria and enterococci isolated from faeces and grown on artificial media to use as personified food additives in IBS treatment. Convincing evidence of the clinical efficacy of autoprobiotic was demonstrated by the disappearance of dyspeptic symptoms. The microbiome of patients with IBS was compared to a group of healthy volunteers and changes in the microbiome after autoprobiotic use were detected by quantitative polymerase chain reaction and 16S rRNA metagenome analysis. The possibility of reducing opportunistic microorganisms in the treatment of IBS with autoprobiotics has been convincingly proven. The quantitative content of enterococci in the intestinal microbiota was higher in IBS patients than in healthy volunteers and increased after therapy. An increase in the relative abundance of genera Coprococcus, Blautia and a decrease in the relative abundance of Paraprevotella spp. were found at the end of therapy. A metabolome study which was performed by gas chromatography and mass spectrometry demonstrated an increase in the content of oxalic acid, a decrease of dodecanoate, lauric acid, and other metabolome components after taking autoprobiotics. Some of these parameters correlated with the relative abundances of Paraprevotella spp., Enterococcus spp., and Coprococcus spp. representative of the microbiome. Apparently, they reflected the peculiarities of metabolic compensation and changes in the microbiota. Therefore, the use of autoprobiotics for treatment of IBS may lead to a stable positive clinical effect, associated with compensatory changes in the intestinal microbiota, and accompanied by corresponding changes in metabolic processes in the organism.PMID:36970947 | DOI:10.3920/BM2022.0053

J Alzheimers Dis. 2023 Mar 23. doi: 10.3233/JAD-221199. Online ahead of print.ABSTRACTBACKGROUND: An increasing number of experimental and clinical studies show a link between Alzheimer's disease and heart diseases such as heart failure, ischemic heart disease, and atrial fibrillation. However, the mechanisms underlying the potential role of amyloid-β (Aβ) in the pathogenesis of cardiac dysfunction in Alzheimer's disease remain unknown. We have recently shown the effects of Aβ 1 - 40 and Aβ 1 - 42 on cell viability and mitochondrial function in cardiomyocytes and coronary artery endothelial cells.OBJECTIVE: In this study, we investigated the effects of Aβ 1 - 40 and Aβ 1 - 42 on the metabolism of cardiomyocytes and coronary artery endothelial cells.METHODS: Gas chromatography-mass spectrometry was used to analyze metabolomic profiles of cardiomyocytes and coronary artery endothelial cells treated with Aβ 1 - 40 and Aβ 1 - 42. In addition, we determined mitochondrial respiration and lipid peroxidation in these cells.RESULTS: We found that the metabolism of different amino acids was affected by Aβ 1 - 42 in each cell type, whereas the fatty acid metabolism is consistently disrupted in both types of cells. Lipid peroxidation was significantly increased, whereas mitochondrial respiration was reduced in both cell types in response to Aβ 1 - 42.CONCLUSION: This study revealed the disruptive effects of Aβ on lipid metabolism and mitochondria function in cardiac cells.PMID:36970904 | DOI:10.3233/JAD-221199

Adv Sci (Weinh). 2023 Mar 27:e2207224. doi: 10.1002/advs.202207224. Online ahead of print.ABSTRACTHeterotopic ossification (HO) is a double-edged sword. Pathological HO presents as an undesired clinical complication, whereas controlled heterotopic bone formation by synthetic osteoinductive materials shows promising therapeutic potentials for bone regeneration. However, the mechanism of material-induced heterotopic bone formation remains largely unknown. Early acquired HO being usually accompanied by severe tissue hypoxia prompts the hypothesis that hypoxia caused by the implantation coordinates serial cellular events and ultimately induces heterotopic bone formation in osteoinductive materials. The data presented herein shows a link between hypoxia, macrophage polarization to M2, osteoclastogenesis, and material-induced bone formation. Hypoxia inducible factor-1α (HIF-1α), a crucial mediator of cellular responses to hypoxia, is highly expressed in an osteoinductive calcium phosphate ceramic (CaP) during the early phase of implantation, while pharmacological inhibition of HIF-1α significantly inhibits M2 macrophage, subsequent osteoclast, and material-induced bone formation. Similarly, in vitro, hypoxia enhances M2 macrophage and osteoclast formation. Osteoclast-conditioned medium enhances osteogenic differentiation of mesenchymal stem cells, such enhancement disappears with the presence of HIF-1α inhibitor. Furthermore, metabolomics analysis reveals that hypoxia enhances osteoclastogenesis via the axis of M2/lipid-loaded macrophages. The current findings shed new light on the mechanism of HO and favor the design of more potent osteoinductive materials for bone regeneration.PMID:36970815 | DOI:10.1002/advs.202207224

Front Microbiol. 2023 Mar 10;14:1149978. doi: 10.3389/fmicb.2023.1149978. eCollection 2023.ABSTRACTINTRODUCTION: The survival of bacterial cells exposed to antibiotics depends on the mode of action, the antibiotics concentration, and the duration of treatment. However, it also depends on the physiological state of the cells and the environmental conditions. In addition, bacterial cultures contain sub-populations that can survive high antibiotic concentrations, so-called persisters. Research on persisters is challenging due to multiple mechanisms for their formation and low fractions, down to and below one millionth of the total cell population. Here, we present an improved version of the persister assay used to enumerate the amount of persisters in a cell population.METHODS: The persister assay with high antibiotic stress exposure was performed at both growth supporting and non-supporting conditions. Escherichia coli cells were pregrown to various growth stages in shake flasks and bench-top bioreactors. In addition, the physiological state of E. coli before antibiotic treatment was determined by quantitative mass spectrometry-based metabolite profiling.RESULTS: Survival of E. coli strongly depended on whether the persister assay medium supported growth or not. The results were also highly dependent on the type of antibiotic and pregrown physiological state of the cells. Therefore, applying the same conditions is critical for consistent and comparable results. No direct connection was observed between antibiotic efficacy to the metabolic state. This also includes the energetic state (i.e., the intracellular concentration of ATP and the adenylate energy charge), which has earlier been hypothesized to be decisive for persister formation.DISCUSSION: The study provides guides and suggestions for the design of future experimentation in the research fields of persisters and antibiotic tolerance.PMID:36970700 | PMC:PMC10036391 | DOI:10.3389/fmicb.2023.1149978

Front Microbiol. 2023 Mar 8;14:1111962. doi: 10.3389/fmicb.2023.1111962. eCollection 2023.ABSTRACTSepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1β. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.PMID:36970673 | PMC:PMC10030955 | DOI:10.3389/fmicb.2023.1111962

Front Microbiol. 2023 Mar 9;14:1093372. doi: 10.3389/fmicb.2023.1093372. eCollection 2023.ABSTRACTThe process of serpentinization supports life on Earth and gives rise to the habitability of other worlds in our Solar System. While numerous studies have provided clues to the survival strategies of microbial communities in serpentinizing environments on the modern Earth, characterizing microbial activity in such environments remains challenging due to low biomass and extreme conditions. Here, we used an untargeted metabolomics approach to characterize dissolved organic matter in groundwater in the Samail Ophiolite, the largest and best characterized example of actively serpentinizing uplifted ocean crust and mantle. We found that dissolved organic matter composition is strongly correlated with both fluid type and microbial community composition, and that the fluids that were most influenced by serpentinization contained the greatest number of unique compounds, none of which could be identified using the current metabolite databases. Using metabolomics in conjunction with metagenomic data, we detected numerous products and intermediates of microbial metabolic processes and identified potential biosignatures of microbial activity, including pigments, porphyrins, quinones, fatty acids, and metabolites involved in methanogenesis. Metabolomics techniques like the ones used in this study may be used to further our understanding of life in serpentinizing environments, and aid in the identification of biosignatures that can be used to search for life in serpentinizing systems on other worlds.PMID:36970670 | PMC:PMC10033605 | DOI:10.3389/fmicb.2023.1093372

Front Microbiol. 2023 Mar 8;14:1140498. doi: 10.3389/fmicb.2023.1140498. eCollection 2023.ABSTRACTINTRODUCTION: The gut microbial community, which can be disturbed or repaired by changes in the internal environment, contributes to the development of acute myocardial infarction (AMI). Gut probiotics play a role in microbiome remodeling and nutritional intervention post-AMI. A newly isolated Lactobacillus johnsonii strain EU03 has shown potential as a probiotic. Here, we investigated the cardioprotective function and mechanism of L. johnsonii through gut microbiome remodeling in AMI rats.METHODS: A rat model of left anterior descending coronary artery ligation (LAD)-mediated AMI was assessed with echocardiography, histology, and serum cardiac biomarkers to evaluate the beneficial effects of L. johnsonii. The immunofluorescence analysis was utilized to visualize the intestinal barrier changes. Antibiotic administration model was used for assessing the gut commensals' function in the improvement of cardiac function post-AMI. The underlying beneficial mechanism through L. johnsonii enrichment was further investigated by metagenomics and metabolomics analysis.RESULTS: A 28-day treatment with L. johnsonii protected cardiac function, delayed cardiac pathology, suppressed myocardial injury cytokines, and improved gut barrier integrity. The microbiome composition was reprogrammed by enhancing the abundance of L. johnsonii. Microbiome dysbiosis by antibiotics abrogated the improvement of cardiac function post-AMI by L. johnsonii. L. johnsonii enrichment caused remodeling of gut microbiome by increasing the abundance of Muribaculaceae, Lactobacillus, and decreasing Romboutsia, Clostridia UCG-014, which were correlated with cardiac traits and serum metabolic biomarkers 16,16-dimethyl-PGA2, and Lithocholate 3-O-glucuronide.CONCLUSION: These findings reveal that gut microbiome remodeling by L. johnsonii ameliorates the cardiac function post-AMI and might advance microbiome-targeted nutritional intervention.Graphical Abstract.PMID:36970663 | PMC:PMC10030800 | DOI:10.3389/fmicb.2023.1140498

Front Microbiol. 2023 Mar 8;14:1022248. doi: 10.3389/fmicb.2023.1022248. eCollection 2023.ABSTRACTINTRODUCTION: The fermentative production of auxin/indole 3-acetate (IAA) using selected Pantoea agglomerans strains can be a promising approach to developing novel plant biostimulants for agriculture use.METHODS: By integrating metabolomics and fermentation technologies, this study aimed to define the optimal culture conditions to obtain auxin/IAA-enriched plant postbiotics using P. agglomerans strain C1. Metabolomics analysis allowed us to demonstrate that the production of a selected.RESULTS AND DISCUSSION: Array of compounds with plant growth-promoting- (IAA and hypoxanthine) and biocontrol activity (NS-5, cyclohexanone, homo-L-arginine, methyl hexadecenoic acid, and indole-3-carbinol) can be stimulated by cultivating this strain on minimal saline medium amended with sucrose as a carbon source. We applied a three-level-two-factor central composite design (CCD) based response surface methodology (RSM) to explore the impact of the independent variables (rotation speed and medium liquid-to-flask volume ratio) on the production of IAA and IAA precursors. The ANOVA component of the CCD indicated that all the process-independent variables investigated significantly impacted the auxin/IAA production by P. agglomerans strain C1. The optimum values of variables were a rotation speed of 180 rpm and a medium liquid-to-flask volume ratio of 1:10. Using the CCD-RSM method, we obtained a maximum indole auxin production of 208.3 ± 0.4 mg IAAequ/L, which was a 40% increase compared to the growth conditions used in previous studies. Targeted metabolomics allowed us to demonstrate that the IAA product selectivity and the accumulation of the IAA precursor indole-3-pyruvic acid were significantly affected by the increase in the rotation speed and the aeration efficiency.PMID:36970660 | PMC:PMC10030972 | DOI:10.3389/fmicb.2023.1022248

Front Bioeng Biotechnol. 2023 Mar 9;11:1150842. doi: 10.3389/fbioe.2023.1150842. eCollection 2023.ABSTRACTBackground: Plant cell culture technology is a potential way to produce polyphenols, however, this way is still trapped in the dilemma of low content and yield. Elicitation is regarded as one of the most effective ways to improve the output of the secondary metabolites, and therefore has attracted extensive attention. Methods: Five elicitors including 5-aminolevulinic acid (5-ALA), salicylic acid (SA), methyl jasmonate (MeJA), sodium nitroprusside (SNP) and Rhizopus Oryzae Elicitor (ROE) were used to improve the content and yield of polyphenols in the cultured Cyclocarya paliurus (C. paliurus) cells, and a co-induction technology of 5-ALA and SA was developed as a result. Meanwhile, the integrated analysis of transcriptome and metabolome was adopted to interpret the stimulation mechanism of co-induction with 5-ALA and SA. Results: Under the co-induction of 50 μM 5-ALA and SA, the content and yield of total polyphenols of the cultured cells reached 8.0 mg/g and 147.12 mg/L, respectively. The yields of cyanidin-3-O-galactoside, procyanidin B1 and catechin reached 28.83, 4.33 and 2.88 times that of the control group, respectively. It was found that expressions of TFs such as CpERF105, CpMYB10 and CpWRKY28 increased significantly, while CpMYB44 and CpTGA2 decreased. These great changes might further make the expression of CpF3'H (flavonoid 3'-monooxygenase), CpFLS (flavonol synthase), CpLAR (leucoanthocyanidin reductase), CpANS (anthocyanidin synthase) and Cp4CL (4-coumarate coenzyme A ligase) increase while CpANR (anthocyanidin reductase) and CpF3'5'H (flavonoid 3', 5'-hydroxylase) reduce, ultimately enhancing the polyphenols accumulation Conclusion: The co-induction of 5-ALA and SA can significantly promote polyphenol biosynthesis in the cultured C. paliurus cells by regulating the expression of key transcription factors and structural genes associated with polyphenol synthesis, and thus has a promising application.PMID:36970633 | PMC:PMC10034720 | DOI:10.3389/fbioe.2023.1150842