PubMed

Front Plant Sci. 2023 May 8;14:1186718. doi: 10.3389/fpls.2023.1186718. eCollection 2023.ABSTRACTElephant grass is widely used in feed production and ecological restoration because of its huge biomass and low occurrence of diseases and insect pets. However, drought seriously affects growth and development of this grass. Strigolactone (SL), a small molecular phytohormone, reportedly participates in improving resilience to cope with arid environment. But the mechanism of SL regulating elephant grass to response to drought stress remains unknown and needs further investigation. We conducted RNA-seq experiments and identified 84,296 genes including 765 and 2325 upregulated differential expression genes (DEGs) and 622 and 1826 downregulated DEGs, compared drought rehydration with spraying SL in roots and leaves, respectively. Combined with targeted phytohormones metabolite analysis, five hormones including 6-BA, ABA, MeSA, NAA, and JA had significant changes under re-watering and spraying SL stages. Moreover, a total of 17 co-expression modules were identified, of which eight modules had the most significant correlation with all physiological indicators with weighted gene co-expression network analysis. The venn analysis revealed the common genes between Kyoto Encyclopedia of Genes and Genomes enriched functional DEGs and the top 30 hub genes of higher weights in eight modules, respectively. Finally, 44 DEGs had been identified as key genes which played a major role in SL response to drought stress. After verification of its expression level by qPCR, six key genes in elephant grass including PpPEPCK, PpRuBPC, PpPGK, PpGAPDH, PpFBA, and PpSBPase genes regulated photosynthetic capacity under the SL treatment to respond to drought stress. Meanwhile, PpACAT, PpMFP2, PpAGT2, PpIVD, PpMCCA, and PpMCCB regulated root development and phytohormone crosstalk to respond to water deficit conditions. Our research led to a more comprehensive understanding about exogenous SL that plays a role in elephant grass response to drought stress and revealed insights into the SL regulating molecular mechanism in plants to adapt to the arid environment.PMID:37223793 | PMC:PMC10200884 | DOI:10.3389/fpls.2023.1186718

Front Plant Sci. 2023 May 8;14:1172857. doi: 10.3389/fpls.2023.1172857. eCollection 2023.ABSTRACTPerennial grains provide various ecosystem services compared to the annual counterparts thanks to their extensive root system and permanent soil cover. However, little is known about the evolution and diversification of perennial grains rhizosphere and its ecological functions over time. In this study, a suite of -OMICSs - metagenomics, enzymomics, metabolomics and lipidomics - was used to compare the rhizosphere environment of four perennial wheat lines at the first and fourth year of growth in comparison with an annual durum wheat cultivar and the parental species Thinopyrum intermedium. We hypothesized that wheat perenniality has a greater role in shaping the rhizobiome composition, biomass, diversity, and activity than plant genotypes because perenniality affects the quality and quantity of C input - mainly root exudates - hence modulating the plant-microbes crosstalk. In support of this hypothesis, the continuous supply of sugars in the rhizosphere along the years created a favorable environment for microbial growth which is reflected in a higher microbial biomass and enzymatic activity. Moreover, modification in the rhizosphere metabolome and lipidome over the years led to changes in the microbial community composition favoring the coexistence of more diverse microbial taxa, increasing plant tolerance to biotic and abiotic stresses. Despite the dominance of the perenniality effect, our data underlined that the OK72 line rhizobiome distinguished from the others by the increase in abundance of Pseudomonas spp., most of which are known as potential beneficial microorganisms, identifying this line as a suitable candidate for the study and selection of new perennial wheat lines.PMID:37223792 | PMC:PMC10200949 | DOI:10.3389/fpls.2023.1172857

Microlife. 2022 Dec 20;4:uqac025. doi: 10.1093/femsml/uqac025. eCollection 2023.ABSTRACTBacterial membrane vesicles (MVs) are abundant in the oceans, but their potential functional roles remain unclear. In this study we characterized MV production and protein content of six strains of Alteromonas macleodii, a cosmopolitan marine bacterium. Alteromonas macleodii strains varied in their MV production rates, with some releasing up to 30 MVs per cell per generation. Microscopy imaging revealed heterogenous MV morphologies, including some MVs aggregated within larger membrane structures. Proteomic characterization revealed that A. macleodii MVs are rich in membrane proteins related to iron and phosphate uptake, as well as proteins with potential functions in biofilm formation. Furthermore, MVs harbored ectoenzymes, such as aminopeptidases and alkaline phosphatases, which comprised up to 20% of the total extracellular enzymatic activity. Our results suggest that A. macleodii MVs may support its growth through generation of extracellular 'hotspots' that facilitate access to essential substrates. This study provides an important basis to decipher the ecological relevance of MVs in heterotrophic marine bacteria.PMID:37223730 | PMC:PMC10117737 | DOI:10.1093/femsml/uqac025

Microlife. 2023 Mar 23;4:uqad010. doi: 10.1093/femsml/uqad010. eCollection 2023.ABSTRACTMicrobial taxonomy is critical for describing ecosystem composition, yet the link between taxonomy and properties of microbes, such as their cellular architecture, remains poorly defined. We hypothesized that the cellular architecture represents microbial niche adaptation. We used cryo-electron microscopy and tomography to analyze microbial morphology in order to associate cellular architecture with phylogeny and genomic contents. As a model system, we chose the core rumen microbiome and imaged a large isolate collection covering 90% of its richness at the order level. Based on quantifications of several morphological features, we found that the visual similarity of microbiota is significantly related to their phylogenetic distance. Up to the Family level, closely related microbes have similar cellular architectures, which are highly correlated with genome similarity. However, in more distantly related bacteria, the correlation both with taxonomy and genome similarity is lost. This is the first comprehensive study of microbial cellular architecture and our results highlight that structure remains an important parameter in classification of microorganisms, along with functional parameters such as metabolomics. Furthermore, the high-quality images presented in this study represent a reference database for the identification of bacteria in anaerobic ecosystems.PMID:37223726 | PMC:PMC10117717 | DOI:10.1093/femsml/uqad010

Research (Wash D C). 2023 Apr 28;6:0127. doi: 10.34133/research.0127. eCollection 2023.ABSTRACTNatural killer (NK) cells, as key immune cells, play essential roles in tumor cell immune escape and immunotherapy. Accumulating evidence has demonstrated that the gut microbiota community affects the efficacy of anti-PD1 immunotherapy and that remodeling the gut microbiota is a promising strategy to enhance anti-PD1 immunotherapy responsiveness in advanced melanoma patients; however, the details of the mechanism remain elusive. In this study, we found that Eubacterium rectale was significantly enriched in melanoma patients who responded to anti-PD1 immunotherapy and that a high E. rectale abundance was related to longer survival in melanoma patients. Furthermore, administration of E. rectale remarkably improved the efficacy of anti-PD1 therapy and increased the overall survival of tumor-bearing mice; moreover, application of E. rectale led to a significant accumulation of NK cells in the tumor microenvironment. Interestingly, conditioned medium isolated from an E. rectale culture system dramatically enhanced NK cell function. Gas chromatography-mass spectrometry/ultrahigh performance liquid chromatography-tandem mass spectrometry-based metabolomic analysis showed that l-serine production was significantly decreased in the E. rectale group; moreover, administration of an l-serine synthesis inhibitor dramatically increased NK cell activation, which enhanced anti-PD1 immunotherapy effects. Mechanistically, supplementation with l-serine or application of an l-serine synthesis inhibitor affected NK cell activation through Fos/Fosl. In summary, our findings reveal the role of bacteria-modulated serine metabolic signaling in NK cell activation and provide a novel therapeutic strategy to improve the efficacy of anti-PD1 immunotherapy in melanoma.PMID:37223471 | PMC:PMC10202379 | DOI:10.34133/research.0127

RSC Adv. 2023 May 22;13(23):15379-15390. doi: 10.1039/d3ra00802a. eCollection 2023 May 22.ABSTRACTLonicera japonica Thunb. has attracted much attention for its treatment of bacterial and viral infectious diseases, while its active ingredients and potential mechanisms of action have not been fully elucidated. Here, we combined metabolomics, and network pharmacology to explore the molecular mechanism of Bacillus cereus ATCC14579 inhibition by Lonicera japonica Thunb. In vitro inhibition experiments showed that the Lonicera japonica Thunb.'s water extracts, ethanolic extract, luteolin, quercetin, and kaempferol strongly inhibited Bacillus cereus ATCC14579. In contrast, chlorogenic acid and macranthoidin B had no inhibitory effect on Bacillus cereus ATCC14579. Meanwhile, the minimum inhibitory concentrations of luteolin, quercetin, and kaempferol against Bacillus cereus ATCC14579 were 15.625 μg mL-1, 31.25 μg mL-1, and 15.625 μg mL-1. Based on the previous experimental basis, the metabolomic analysis showed the presence of 16 active ingredients in Lonicera japonica Thunb.'s water extracts and ethanol extracts, with differences in the luteolin, quercetin, and kaempferol contents between the water extracts and ethanol extracts. Network pharmacology studies indicated that fabZ, tig, glmU, secA, deoD, nagB, pgi, rpmB, recA, and upp were potential key targets. Active ingredients of Lonicera japonica Thunb. may exert their inhibitory effects by inhibiting ribosome assembly, the peptidoglycan biosynthesis process, and the phospholipid biosynthesis process of Bacillus cereus ATCC14579. An alkaline phosphatase activity assay, peptidoglycan concentration assay, and protein concentration assay showed that luteolin, quercetin, and kaempferol disrupted the Bacillus cereus ATCC14579 cell wall and cell membrane integrity. Transmission electron microscopy results showed significant changes in the morphology and ultrastructure of the cell wall and cell membrane of Bacillus cereus ATCC14579, further confirming the disruption of the cell wall and cell membrane integrity of Bacillus cereus ATCC14579 by luteolin, quercetin, and kaempferol. In conclusion, Lonicera japonica Thunb. can be used as a potential antibacterial agent for Bacillus cereus ATCC14579, which may exert its antibacterial activity by destroying the integrity of the cell wall and membrane.PMID:37223411 | PMC:PMC10201548 | DOI:10.1039/d3ra00802a

Infect Drug Resist. 2023 May 18;16:3073-3084. doi: 10.2147/IDR.S405033. eCollection 2023.ABSTRACTBACKGROUND: Qiguiyin decoction (QGYD) was a traditional Chinese medicine (TCM) used to treat Pseudomonas aeruginosa infection in China. This study investigated the therapeutic effect and the potential mechanism of QGYD on carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection.MATERIALS AND METHODS: Pulmonary infections were induced in mice by CRPA. The therapeutic effect of QGYD was evaluated by lung index and pulmonary pathology. The potential effects of QGYD on intestinal flora were detected by gut microbiome. The overall metabolism regulation of QGYD in blood was investigated by metabonomics. Next, the correlation between intestinal flora and metabolites was analyzed to illustrate the relationship between the regulatory effects of QGYD on metabolites and the beneficial effects of intestinal flora.RESULTS: QGYD has significant therapeutic effect on CRPA infection. QGYD profoundly inhibited the excessive accumulation of Deferribacteres and Mucispirillum at phylum and genus levels, respectively. Eleven potential metabolites that were abnormally expressed by CRPA infection and significantly reversed by QGYD were identified. Ten of the eleven metabolites significantly regulated by QGYD were related to Deferribacteres. Deferribacteres showed significant positive correlation with DL-lactic acid, phenylalanine and other metabolites and significant negative correlation with vitamin k1. At the genus level, Mucispirillum was closely related to metabolites significantly regulated by QGYD. Mucispirillum was positively correlated with metabolites such as Dl-lactate and negatively correlated with vitamin k1.CONCLUSION: QGYD can improve CRPA infection and has the effect of regulating intestinal flora and metabolism. It was a promising drug against infection.PMID:37222987 | PMC:PMC10202261 | DOI:10.2147/IDR.S405033

Chin J Integr Med. 2023 May 24. doi: 10.1007/s11655-023-3552-0. Online ahead of print.ABSTRACTOBJECTIVE: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics.METHODS: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively.RESULTS: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on.CONCLUSION: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.PMID:37222828 | DOI:10.1007/s11655-023-3552-0

J Neurochem. 2023 May 24. doi: 10.1111/jnc.15845. Online ahead of print.ABSTRACTWhite matter hyperintensities (WMH) are the most compelling risk factors of stroke, dementia, and early mortality. We aimed to investigate the associations between WMH and circulating metabolites. We studied up to 8190 individuals from the UK Biobank, who have both measurements of 249 plasma metabolites and WMH volume. Linear regression models were applied in pooled samples, and age-stratified and sex-stratified subsamples to estimate the associations between WMH and metabolomic measures. We conducted three analytic models. In the basic model, we identified 45 metabolomic measures associated with WMH after multiple testing correction (p < 0.0022), 15 of which remained significant in additional adjustments, but no metabolites passed the full adjustment in pooled samples. The 15 WMH-related metabolites were subfractions of various sizes of high-density lipoprotein (HDL), fatty acids, and glycoprotein acetyls. Among them, one fatty acid metabolite and 12 HDL-related traits showed significant negative associations with WMH. Higher glycoprotein acetyls were associated with large WMH. Strong age and sex specificities were observed indicating distinct metabolomic features accompany WMH in different samples. More metabolites were identified in males and adults under 50 years old. Circulating metabolites showed remarkably widespread associations with WMH. Population specificities may shed light on the different pertinent implications of WMH.PMID:37222503 | DOI:10.1111/jnc.15845

Hepatology. 2023 May 25. doi: 10.1097/HEP.0000000000000474. Online ahead of print.ABSTRACTThere is great interest in identifying microbiome features as reliable noninvasive diagnostic and/or prognostic biomarkers for non-cirrhotic NASH fibrosis. Several cross-sectional studies have reported gut microbiome features associated with advanced NASH fibrosis and cirrhosis, where the most prominent features are associated with cirrhosis. However, no large, prospectively collected data exist establishing microbiome features that discern non-cirrhotic NASH fibrosis, integrate the fecal metabolome as disease biomarkers, and are unconfounded by BMI and age. Results from shotgun metagenomic sequencing performed on fecal samples prospectively collected from 279 US patients with biopsy-proven NASH (F1-F3 fibrosis) enrolled in the REGENERATE I303 study were compared to those from three healthy control cohorts and integrated with the absolute quantification of fecal bile acids. Microbiota beta-diversity was different, and BMI- and age-adjusted logistic regression identified 12 NASH-associated species. Random forest prediction models resulted in an AUC of 0.75 to 0.81 in a receiver operator characteristic analysis. Additionally, specific fecal bile acids were significantly lower in NASH and correlated with plasma C4 levels. Microbial gene abundance analysis revealed 127 genes increased in controls, many involving protein synthesis, whereas 362 genes were increased in NASH many involving bacterial environmental responses (FDR < 0.01). Finally, we provide evidence that fecal bile acid levels may be a better discriminator of non-cirrhotic NASH versus health than either plasma bile acids or gut microbiome features. These results may have value as a set of baseline characteristics of non-cirrhotic NASH against which therapeutic interventions to prevent cirrhosis can be compared and microbiome-based diagnostic biomarkers identified.PMID:37222264 | DOI:10.1097/HEP.0000000000000474

CNS Neurosci Ther. 2023 May 24. doi: 10.1111/cns.14253. Online ahead of print.ABSTRACTAIMS: This metabolomic study aimed to evaluate the role of N-acetylneuraminic acid (Neu5Ac) in the neurological deficits of normal pressure hydrocephalus (NPH) and its potential therapeutic effect.METHODS: We analyzed the metabolic profiles of NPH using cerebrospinal fluid with multivariate and univariate statistical analyses in a set of 42 NPH patients and 38 controls. We further correlated the levels of differential metabolites with severity-related clinical parameters, including the normal pressure hydrocephalus grading scale (NPHGS). We then established kaolin-induced hydrocephalus in mice and treated them using N-acetylmannosamine (ManNAc), a precursor of Neu5Ac. We examined brain Neu5Ac, astrocyte polarization, demyelination, and neurobehavioral outcomes to explore its therapeutic effect.RESULTS: Three metabolites were significantly altered in NPH patients. Only decreased Neu5Ac levels were correlated with NPHGS scores. Decreased brain Neu5Ac levels have been observed in hydrocephalic mice. Increasing brain Neu5Ac by ManNAc suppressed the activation of astrocytes and promoted their transition from A1 to A2 polarization. ManNAc also attenuated the periventricular white matter demyelination and improved neurobehavioral outcomes in hydrocephalic mice.CONCLUSION: Increasing brain Neu5Ac improved the neurological outcomes associated with the regulation of astrocyte polarization and the suppression of demyelination in hydrocephalic mice, which may be a potential therapeutic strategy for NPH.PMID:37222223 | DOI:10.1111/cns.14253

J Periodontal Res. 2023 May 23. doi: 10.1111/jre.13140. Online ahead of print.ABSTRACTBACKGROUND/AIMS: Hyperglycemia in diabetes is closely associated with periodontal disease progression. This study aimed to investigate the effect of hyperglycemia on the barrier function of gingival epithelial cells as a cause of hyperglycemia-exacerbated periodontitis in diabetes mellitus.METHODS: The abnormal expression of adhesion molecules in gingival epithelium in diabetes was compared between db/db and control mice. To study the effects of hyperglycemia on interepithelial cell permeability, the mRNA and protein expressions of adhesion molecules were investigated using a human gingival epithelial cell line (epi 4 cells) in the presence of either 5.5 mM glucose (NG) or 30 mM glucose (HG). Immunocytochemical and histological analyses were performed. We also studied HG-related intracellular signaling to assess abnormal adhesion molecule expression in the cultured epi 4 cells.RESULTS: The results of the proteomic analysis implied the abnormal regulation of cell-cell adhesion, and mRNA and protein expression assessments revealed the significant downregulation of Claudin1 expression in the gingival tissues of db/db mice (p < .05 vs control). Similarly, the mRNA and protein expressions of adhesion molecules were lower in epi 4 cells cultured under HG conditions than in those cultured under NG conditions (p < .05). Three-dimensional culture and transmission electron microscopy revealed reduced thickness of the epithelial cell layers with no flattened apical cells and heterogeneously arranged intercellular spaces among adjacent epi 4 cells under the HG. These results were consistent with the increased permeability of epi 4 cells under the HG relative to that of cells under the NG. This abnormal expression of intercellular adhesion molecules under the HG was related to the increased expression of receptors for advanced glycation end products (AGEs) and oxidative stress relative to that seen under the NG, along with stimulation of ERK1/2 phosphorylation in epi 4 cells.CONCLUSIONS: High glucose-induced impairment of intercellular adhesion molecule expression in gingival epithelial cells was related to the intercellular permeability of gingival cells, representing a possible link to hyperglycemia-related AGE signaling, oxidative stress, and ERK1/2 activation.PMID:37221815 | DOI:10.1111/jre.13140

BMC Bioinformatics. 2023 May 23;24(1):214. doi: 10.1186/s12859-023-05342-9.ABSTRACTBACKGROUND: A variety of high-throughput analyses, such as transcriptome, proteome, and metabolome analysis, have been developed, producing unprecedented amounts of omics data. These studies generate large gene lists, of which the biological significance shall be deeply understood. However, manually interpreting these lists is difficult, especially for non-bioinformatics-savvy scientists.RESULTS: We developed an R package and a corresponding web server-Genekitr, to assist biologists in exploring large gene sets. Genekitr comprises four modules: gene information retrieval, ID (identifier) conversion, enrichment analysis and publication-ready plotting. Currently, the information retrieval module can retrieve information on up to 23 attributes for genes of 317 organisms. The ID conversion module assists in ID-mapping of genes, probes, proteins, and aliases. The enrichment analysis module organizes 315 gene set libraries in different biological contexts by over-representation analysis and gene set enrichment analysis. The plotting module performs customizable and high-quality illustrations that can be used directly in presentations or publications.CONCLUSIONS: This web server tool will make bioinformatics more accessible to scientists who might not have programming expertise, allowing them to perform bioinformatics tasks without coding.PMID:37221491 | DOI:10.1186/s12859-023-05342-9

BMC Plant Biol. 2023 May 24;23(1):273. doi: 10.1186/s12870-023-04280-1.NO ABSTRACTPMID:37221477 | DOI:10.1186/s12870-023-04280-1

Harmful Algae. 2023 Jun;125:102430. doi: 10.1016/j.hal.2023.102430. Epub 2023 Mar 25.ABSTRACTFreshwater cyanobacteria are known worldwide for their potential to produce toxins. However, these organisms are also found in marine, terrestrial and extreme environments and produce unique compounds, other than toxins. Nevertheless, their effects on biological systems are still barely known. This work tested extracts of different cyanobacterial strains against zebrafish (Danio rerio) larvae and analyzed their metabolomic profiles using liquid chromatography combined with mass spectrometry. Strains Desertifilum tharense, Anagnostidinema amphibium, and Nostoc sp. promoted morphological abnormalities such as pericardial edema, edema in the digestive system region, curvature of the tail and spine in zebrafish larvae in vivo. In contrast, Microcystis aeruginosa and Chlorogloeopsis sp. did not promote such changes. Metabolomics revealed unique compounds belonging to the classes of terpenoids, peptides, and linear lipopeptides/microginins in the nontoxic strains. The toxic strains were shown to contain unique compounds belonging to the classes of cyclic peptides, amino acids and other peptides, anabaenopeptins, lipopeptides, terpenoids, and alkaloids and derivatives. Other unknown compounds were also detected, highlighting the rich structural diversity of secondary metabolites produced by cyanobacteria. The effects of cyanobacterial metabolites on living organisms, mainly those related to potential human and ecotoxicological risks, are still poorly known. This work highlights the diverse, complex, and unique metabolomic profiles of cyanobacteria and the biotechnological potential and associated risks of exposure to their metabolites.PMID:37220983 | DOI:10.1016/j.hal.2023.102430

BMB Rep. 2023 May 24:5912. Online ahead of print.ABSTRACTThis study investigates the relationship between cancer cachexia and the gut microbiota, focusing on the influence of cancer on microbial composition. Lewis lung cancer cell allografts were used to induce cachexia in mice, and body and muscle weight changes were monitored. Fecal samples were collected for targeted metabolomic analysis for short chain fatty acids and microbiome analysis. The cachexia group exhibited lower alpha diversity and distinct beta diversity in gut microbiota compared to the control group. Differential abundance analysis revealed higher Bifidobacterium and Romboutsia, but lower Streptococcus abundance in the cachexia group. Additionally, lower proportions of acetate and butyrate were observed in the cachexia group. The study observed that a significant impact of cancer cachexia on gut microbiota and their generated metabolites, indicating the host-to-gut microbiota axis.PMID:37220909

aBIOTECH. 2023 Jan 11;4(1):47-56. doi: 10.1007/s42994-022-00091-4. eCollection 2023 Mar.ABSTRACTPlants are the most important sources of food for humans, as well as supplying many ingredients that are of great importance for human health. Developing an understanding of the functional components of plant metabolism has attracted considerable attention. The rapid development of liquid chromatography and gas chromatography, coupled with mass spectrometry, has allowed the detection and characterization of many thousands of metabolites of plant origin. Nowadays, elucidating the detailed biosynthesis and degradation pathways of these metabolites represents a major bottleneck in our understanding. Recently, the decreased cost of genome and transcriptome sequencing rendered it possible to identify the genes involving in metabolic pathways. Here, we review the recent research which integrates metabolomic with different omics methods, to comprehensively identify structural and regulatory genes of the primary and secondary metabolic pathways. Finally, we discuss other novel methods that can accelerate the process of identification of metabolic pathways and, ultimately, identify metabolite function(s).PMID:37220537 | PMC:PMC10199974 | DOI:10.1007/s42994-022-00091-4

PeerJ. 2023 May 18;11:e15302. doi: 10.7717/peerj.15302. eCollection 2023.ABSTRACTBACKGROUND: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma.METHODS: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers.RESULTS: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid.CONCLUSIONS: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.PMID:37220527 | PMC:PMC10200095 | DOI:10.7717/peerj.15302

Plant Physiol. 2023 May 23:kiad298. doi: 10.1093/plphys/kiad298. Online ahead of print.ABSTRACTAcclimation and adaptation of metabolism to a changing environment are key processes for plant survival and reproductive success. In the present study, 241 natural accessions of Arabidopsis (Arabidopsis thaliana) were grown under two different temperature regimes, 16 °C and 6 °C, and growth parameters were recorded, together with metabolite profiles, to investigate the natural genome × environment effects on metabolome variation. The plasticity of metabolism, which was captured by metabolic distance measures, varied considerably between accessions. Both relative growth rates and metabolic distances were predictable by the underlying natural genetic variation of accessions. Applying machine learning methods, climatic variables of the original growth habitats were tested for their predictive power of natural metabolic variation among accessions. We found specifically habitat temperature during the first quarter of the year to be the best predictor of the plasticity of primary metabolism, indicating habitat temperature as the causal driver of evolutionary cold adaptation processes. Analyses of epigenome- and genome-wide associations revealed accession-specific differential DNA-methylation levels as potentially linked to the metabolome and identified FUMARASE2 as strongly associated with cold adaptation in Arabidopsis accessions. These findings were supported by calculations of the biochemical Jacobian matrix based on variance and covariance of metabolomics data, which revealed that growth under low temperatures most substantially affects the accession-specific plasticity of fumarate and sugar metabolism. Our findings indicate that the plasticity of metabolic regulation is predictable from the genome and epigenome and driven evolutionarily by Arabidopsis growth habitats.PMID:37220420 | DOI:10.1093/plphys/kiad298

Anal Chem. 2023 May 23. doi: 10.1021/acs.analchem.2c05371. Online ahead of print.ABSTRACTIn recent years, feces has surfaced as the matrix of choice for investigating the gut microbiome-health axis because of its non-invasive sampling and the unique reflection it offers of an individual's lifestyle. In cohort studies where the number of samples required is large, but availability is scarce, a clear need exists for high-throughput analyses. Such analyses should combine a wide physicochemical range of molecules with a minimal amount of sample and resources and downstream data processing workflows that are as automated and time efficient as possible. We present a dual fecal extraction and ultra high performance liquid chromatography-high resolution-quadrupole-orbitrap-mass spectrometry (UHPLC-HR-Q-Orbitrap-MS)-based workflow that enables widely targeted and untargeted metabolome and lipidome analysis. A total of 836 in-house standards were analyzed, of which 360 metabolites and 132 lipids were consequently detected in feces. Their targeted profiling was validated successfully with respect to repeatability (78% CV < 20%), reproducibility (82% CV < 20%), and linearity (81% R2 > 0.9), while also enabling holistic untargeted fingerprinting (15,319 features, CV < 30%). To automate targeted processing, we optimized an R-based targeted peak extraction (TaPEx) algorithm relying on a database comprising retention time and mass-to-charge ratio (360 metabolites and 132 lipids), with batch-specific quality control curation. The latter was benchmarked toward vendor-specific targeted and untargeted software and our isotopologue parameter optimization/XCMS-based untargeted pipeline in LifeLines Deep cohort samples (n = 97). TaPEx clearly outperformed the untargeted approaches (81.3 vs 56.7-66.0% compounds detected). Finally, our novel dual fecal metabolomics-lipidomics-TaPEx method was successfully applied to Flemish Gut Flora Project cohort (n = 292) samples, leading to a sample-to-result time reduction of 60%.PMID:37220321 | DOI:10.1021/acs.analchem.2c05371