PubMed

Nucleic Acids Res. 2023 May 11:gkad407. doi: 10.1093/nar/gkad407. Online ahead of print.ABSTRACTMicrobiome studies have become routine in biomedical, agricultural and environmental sciences with diverse aims, including diversity profiling, functional characterization, and translational applications. The resulting complex, often multi-omics datasets demand powerful, yet user-friendly bioinformatics tools to reveal key patterns, important biomarkers, and potential activities. Here we introduce MicrobiomeAnalyst 2.0 to support comprehensive statistics, visualization, functional interpretation, and integrative analysis of data outputs commonly generated from microbiome studies. Compared to the previous version, MicrobiomeAnalyst 2.0 features three new modules: (i) a Raw Data Processing module for amplicon data processing and taxonomy annotation that connects directly with the Marker Data Profiling module for downstream statistical analysis; (ii) a Microbiome Metabolomics Profiling module to help dissect associations between community compositions and metabolic activities through joint analysis of paired microbiome and metabolomics datasets; and (iii) a Statistical Meta-Analysis module to help identify consistent signatures by integrating datasets across multiple studies. Other important improvements include added support for multi-factor differential analysis and interactive visualizations for popular graphical outputs, updated methods for functional prediction and correlation analysis, and expanded taxon set libraries based on the latest literature. These new features are demonstrated using a multi-omics dataset from a recent type 1 diabetes study. MicrobiomeAnalyst 2.0 is freely available at microbiomeanalyst.ca.PMID:37166960 | DOI:10.1093/nar/gkad407

Transgenic Res. 2023 May 11. doi: 10.1007/s11248-023-00347-9. Online ahead of print.ABSTRACTExhaustive analysis of genetically modified crops over multiple decades has increased societal confidence in the technology. New Plant Breeding Techniques are now emerging with improved precision and the ability to generate products containing no foreign DNA and mimic/replicate conventionally bred varieties. In the present study, metabolomic analysis was used to compare (i) tobacco genotypes with and without the CRISPR associated protein 9 (Cas9), (ii) tobacco lines with the edited and non-edited DE-ETIOLATED-1 gene without phenotype and (iii) leaf and fruit tissue from stable non-edited tomato progeny with and without the Cas9. In all cases, multivariate analysis based on the difference test using LC-HRMS/MS and GC-MS data indicated no significant difference in their metabolomes. The variations in metabolome composition that were evident could be associated with the processes of tissue culture regeneration and/or transformation (e.g. interaction with Agrobacterium). Metabolites responsible for the variance included quantitative changes of abundant, well characterised metabolites such as phenolics (e.g. chlorogenic acid) and several common sugars such as fructose. This study provides fundamental data on the characterisation of gene edited crops, that are important for the evaluation of the technology and its assessment. The approach also suggests that metabolomics could contribute to routine product-based analysis of crops/foods generated from New Plant Breeding approaches.PMID:37166587 | DOI:10.1007/s11248-023-00347-9

FEBS J. 2023 May 11. doi: 10.1111/febs.16816. Online ahead of print.ABSTRACTAstrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis, and synaptic transmission. They are also the major source of L-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. L-serine is the precursor of the two main co-agonists of the N-methyl-D-aspartate receptor, glycine and D-serine. Strikingly, dysfunctions in both L- and D-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular level of L-serine, glycine, threonine, L- and D-aspartate (which level is unexpectedly higher than that of D-serine) show the same biosynthetic time course. A significant utilization of L-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocytes differentiation, highlight that D-serine synthesis is restricted in differentiated astrocytes, and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations.PMID:37166453 | DOI:10.1111/febs.16816

Gerontology. 2023 Apr 25. doi: 10.1159/000530795. Online ahead of print.ABSTRACTMeasuring the abundance of biological molecules and their chemical modifications in blood and tissues has been the cornerstone of research and medical diagnoses for decades. Although the number and variety of molecules that can be measured have expanded exponentially, the blood biomarkers routinely assessed in medical practice remain limited to a few dozen, which have not substantially changed over the last 30-40 years. The discovery of novel biomarkers would allow, for example, risk stratification or monitoring of disease progression or the effectiveness of treatments and interventions, improving clinical practice in myriad ways. In this review, we combine the biomarker discovery concept with geroscience. Geroscience bridges aging research and translation to clinical applications by combining the framework of medical gerontology with high-technology medical research. With the development of geroscience and the rise of blood biomarkers, there has been a paradigm shift from disease prevention and cure to promoting health and healthy aging. New -omic technologies have played a role in the development of blood biomarkers, including epigenetic, proteomic, metabolomic, and lipidomic markers, which have emerged as correlates or predictors of health status, from disease and exceptional health.PMID:37166337 | DOI:10.1159/000530795

J Virol. 2023 May 11:e0058023. doi: 10.1128/jvi.00580-23. Online ahead of print.ABSTRACTHepatitis B virus (HBV) infection affects hepatic metabolism. Serum metabolomics studies have suggested that HBV possibly hijacks the glycerol-3-phosphate (G3P) shuttle. In this study, the two glycerol-3-phosphate dehydrogenases (GPD1 and GPD2) in the G3P shuttle were analyzed for determining their role in HBV replication and the findings revealed that GPD2 and not GPD1 inhibited HBV replication. The knockdown of GPD2 expression upregulated HBV replication, while GPD2 overexpression reduced HBV replication. Moreover, the overexpression of GPD2 significantly reduced HBV replication in hydrodynamic injection-based mouse models. Mechanistically, this inhibitory effect is related to the GPD2-mediated degradation of HBx protein by recruiting the E3 ubiquitin ligase TRIM28 and not to the alterations in G3P metabolism. In conclusion, this study revealed GPD2, a key enzyme in the G3P shuttle, as a host restriction factor in HBV replication. IMPORTANCE The glycerol-3-phosphate (G3P) shuttle is important for the delivery of cytosolic reducing equivalents into mitochondria for oxidative phosphorylation. The study analyzed two key components of the G3P shuttle and identified GPD2 as a restriction factor in HBV replication. The findings revealed a novel mechanism of GPD2-mediated inhibition of HBV replication via the recruitment of TRIM28 for degrading HBx, and the HBx-GPD2 interaction could be another potential therapeutic target for anti-HBV drug development.PMID:37166302 | DOI:10.1128/jvi.00580-23

Food Funct. 2023 May 11. doi: 10.1039/d3fo00692a. Online ahead of print.ABSTRACTSelenium (Se), a well-known antioxidant, is important for male fertility and sperm quality. The gut microbiota is involved in vital activities and cross-talk between reproduction and the gut axis. It is still unclear whether the gut microbiota mediates the impact of selenium on semen quality, and what the underlying mechanisms may be. A selenized glucose (SeGlu) derivative is a novel organic Se compound. After 7 days of acclimation, the Sprague-Dawley (SD) male rats (230 g, 6 weeks) were divided into three drinking groups: deionized water group (CK), SeGlu 0.15 group (0.15 mg Se per L), and SeGlu 0.4 group (0.4 mg Se per L). All animals were euthanized 30 days post-treatment. Serum and intratesticular testosterone and semen parameters were measured. Metagenomic and non-targeted metabolomic approaches were used to study the effects of SeGlu on the gut microbiota and serum metabolites of rats. In both the SeGlu 0.15 Group and the SeGlu 0.4 Group, we found a significant increase in seminiferous epithelium thickness. While the SeGlu 0.4 Group had a tendency to increase with insignificant difference, the SeGlu 0.15 Group significantly improved the sperm viability, survival rate, and seminal plasma fructose. SeGlu had no effect on intratesticular testosterone levels, or abnormal sperm counts. Measured serum testosterone levels using ELISA and LC-MS, which showed a decreasing trend. ELISA did not reveal significant differences, but LC-MS indicated a significant decrease in SeGlu 0.4 group. Meanwhile, the SeGlu 0.15 Group reduced the abundance of harmful bacteria such as Rikenella, Barnesiella, Tenacibaculum, and Aeromonas while increasing the abundance of beneficial microbiota such as Intestinimonas, Christensenella, Coprococcus, and Butyrivibrio. Linear discriminant analysis Effect Size (LEfSe) identified the SeGlu 0.15 group's feature genera as Roseburia, Clostridium, Ruminococcus, and Eubacterium. Serum metabolites showed that the SeGlu 0.15 Group increased 5 beta-androstane-3,17-dione while decreasing estrone and 2-methoxyestradiol (2-MeOE2). In conclusion, the SeGlu 0.15 Group can significantly alter the levels of several sex hormones in serum, improve the quality of rats' sperm, and reduce harmful bacterial colonization. SeGlu 0.15 may be used as an effective dietary supplement.PMID:37166164 | DOI:10.1039/d3fo00692a

Adv Sci (Weinh). 2023 May 11:e2300806. doi: 10.1002/advs.202300806. Online ahead of print.ABSTRACTPoor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig -treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD-L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti-PD-L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo-immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced.PMID:37166035 | DOI:10.1002/advs.202300806

Plant Genome. 2023 May 10:e20337. doi: 10.1002/tpg2.20337. Online ahead of print.ABSTRACTDrought is one of the major constraints limiting chickpea productivity. To unravel complex mechanisms regulating drought response in chickpea, we generated transcriptomics, proteomics, and metabolomics datasets from root tissues of four contrasting drought-responsive chickpea genotypes: ICC 4958, JG 11, and JG 11+ (drought-tolerant), and ICC 1882 (drought-sensitive) under control and drought stress conditions. Integration of transcriptomics and proteomics data identified enriched hub proteins encoding isoflavone 4'-O-methyltransferase, UDP-d-glucose/UDP-d-galactose 4-epimerase, and delta-1-pyrroline-5-carboxylate synthetase. These proteins highlighted the involvement of pathways such as antibiotic biosynthesis, galactose metabolism, and isoflavonoid biosynthesis in activating drought stress response mechanisms. Subsequently, the integration of metabolomics data identified six metabolites (fructose, galactose, glucose, myoinositol, galactinol, and raffinose) that showed a significant correlation with galactose metabolism. Integration of root-omics data also revealed some key candidate genes underlying the drought-responsive "QTL-hotspot" region. These results provided key insights into complex molecular mechanisms underlying drought stress response in chickpea.PMID:37165696 | DOI:10.1002/tpg2.20337

Curr Vasc Pharmacol. 2023 May 10. doi: 10.2174/1570161121666230510141338. Online ahead of print.ABSTRACTCardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential risk-enhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of "omics" technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.PMID:37165508 | DOI:10.2174/1570161121666230510141338

Curr Med Chem. 2023 May 9. doi: 10.2174/0929867330666230509110111. Online ahead of print.ABSTRACTINTRODUCTION: Circulating microRNAs (miRNAs) serve as noninvasive diagnostic markers in many cancers. This meta-analysis aims to evaluate the diagnostic efficacy of circulating microRNAs for melanoma.MATERIAL AND METHODS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and ROC curve were evaluated using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software packages. To investigate the heterogeneity, the I2 and Chi-square tests were used. The publishing bias was evaluated using Begg's rank correlation and Egger regression asymmetry tests.RESULTS: A total of 9 articles covering 13 studies (more than 50 miRs individually and in combination) were included, containing 1,355 participants (878 cases and 477 controls). The overall pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and AUC were 0.78 (95% CI: 0.76-0.81), 0.80 (95% CI: 0.77-0.83), 4.32 (95% CI: 3.21-5.82), 0.17 (95% CI: 0.09-0.32), 28.0 (95% CI: 15.34-51.09), and 0.91, respectively. According to Begg's and Egger's tests, there was no publication bias (Begg's p = 0.160 and Egger's p = 0.289).CONCLUSION: Circulating miRNAs can serve as fair and non-invasive diagnostic biomarkers for melanoma. Additionally, specific miRNAs still need to be discovered for diagnosing melanoma.PMID:37165504 | DOI:10.2174/0929867330666230509110111

Curr Med Chem. 2023 May 9. doi: 10.2174/0929867330666230509110108. Online ahead of print.ABSTRACTIdentifying metabolic signatures induced by the immune response to vaccines allows to discriminate vaccinated from non-vaccinated subjects and decipher the molecular mechanisms associated with the host immune response. This review illustrates and discusses the results of metabolomics-based studies on the innate and adaptive immune response to vaccines, long-term functional reprogramming (immune memory), and adverse reactions. Glycolysis is not overexpressed by vaccines, suggesting that the immune cell response to vaccinations does not require rapid energy availability as that is necessary during an infection. Vaccines strongly impact lipids metabolism, including saturated or unsaturated fatty acids, inositol phosphate, and cholesterol. Cholesterol is strategic for synthesizing 25-hydroxycholesterol in activated macrophages and dendritic cells and stimulates the conversion of macrophages and T cells in M2 macrophage and Treg, respectively. In conclusion, the large-scale application of metabolomics enables the identification of candidate predictive biomarkers of vaccine efficacy/tolerability.PMID:37165503 | DOI:10.2174/0929867330666230509110108

Harmful Algae. 2023 May;124:102406. doi: 10.1016/j.hal.2023.102406. Epub 2023 Feb 18.ABSTRACTAs a tropical filamentous cyanobacterium, Raphidiopsis raciborskii has attracted much attention due to its expansion and toxin production. However, the mechanisms of its expansion to temperate regions have not been studied in detail. To address the potential strategies, the physiological and metabolomic profiles of R. raciborskii FACHB 1096 isolated from a temperate lake in China were determined and measured at different temperatures (10 °C, 15 °C, 20 °C, 25 °C, and 32 °C). The results demonstrated that temperature significantly changed cell viability, chlorophyll a content, specific growth rate, Chl a fluorescence, and filamentous shape of R. raciborskii. Low temperature decreased cell viability, specific growth rate, and photosynthetic efficiency, while the proportion of akinete and carbon fixation per unit cell were significantly increased compared with high temperature (32 °C). A constructed unimodal model indicated that filament length, cell volume, and cell length/width of R. raciborskii were significantly reduced in both high and low temperature environments. Under low-temperature conditions, R. raciborskii suffered different degrees of oxidative damage and produced corresponding antioxidant substances to resist oxidative stress, suggesting that low temperature changes the metabolic level of the cells, causing the cells to gradually switch from development to defense. Metabolomic data further confirmed that temperature change induced shifts in metabolic pathways in R. raciborskii, including starch and sucrose metabolic pathways, glutathione metabolic pathways, and the pentose phosphate pathways (PPP), as well as metabolic pathways related to the tricarboxylic acid (TCA) cycle. Our results indicated that the trade-offs of R. raciborskii cells among the growth, cell size, and metabolites can be significantly regulated by temperature, with broad implications for its global expansion in temperate waterbodies.PMID:37164561 | DOI:10.1016/j.hal.2023.102406

Int J Spine Surg. 2023 May 10:8502. doi: 10.14444/8502. Online ahead of print.ABSTRACTAdult spinal deformity (ASD) surgery is still associated with high surgical risks. Machine learning algorithms applied to multicenter databases have been created to predict outcomes and complications, optimize patient selection, and improve overall results. However, the multiple data points currently used to create these models allow for 70% of accuracy in prediction. We need to find new variables that can capture the spectrum of probability that is escaping from our control. These proposed variables are based on patients' biological dimensions, such as frailty, sarcopenia, muscle and bone (tissue) sampling, serological assessment of cellular senescence, and circulating biomarkers that can measure epigenetics, inflammaging, and -omics. Many of these variables are proven to be modifiable and could be improved with proper nutrition, toxin avoidance, endurance exercise, and even surgery. The purpose of this manuscript is to describe the different future data points that can be implemented in ASD assessment to improve modeling prediction, allow monitoring their response to prerehabilitation programs, and improve patient counseling.PMID:37164480 | DOI:10.14444/8502

Eur J Prev Cardiol. 2023 Apr 28:zwad113. doi: 10.1093/eurjpc/zwad113. Online ahead of print.ABSTRACTAIMS: To evaluate the associations of dietary indices and quantitative cardiorespiratory fitness (CRF) measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.METHODS AND RESULTS: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO2) and completed semi-quantitative food frequency questionnaires. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified. In 2380 FHS participants (54 ± 9 years, 54% female, body mass index 28 ± 5 kg/m2), 1 SD higher AHEI and MDS were associated with 5.2% (1.2 mL/kg/min, 95% CI 4.3-6.0%, P < 0.0001) and 4.5% (1.0 mL/kg/min, 95% CI 3.6-5.3%, P < 0.0001) greater peak VO2 in linear models adjusted for age, sex, total daily energy intake, cardiovascular risk factors, and physical activity. In participants with metabolite profiling (N = 1154), 24 metabolites were concordantly associated with both dietary indices and peak VO2 in multivariable-adjusted linear models (FDR < 5%). Metabolites that were associated with lower CRF and poorer dietary quality included C6 and C7 carnitines, C16:0 ceramide, and dimethylguanidino valeric acid, and metabolites that were positively associated with higher CRF and favourable dietary quality included C38:7 phosphatidylcholine plasmalogen and C38:7 and C40:7 phosphatidylethanolamine plasmalogens.CONCLUSION: Higher diet quality is associated with greater CRF cross-sectionally in a middle-aged community-dwelling sample, and metabolites highlight potential shared favourable effects on cardiometabolic health.PMID:37164358 | DOI:10.1093/eurjpc/zwad113

Food Chem Toxicol. 2023 May 8:113817. doi: 10.1016/j.fct.2023.113817. Online ahead of print.ABSTRACTNanoplastics is a major environmental concern and may cause potential harm to organisms. Previous studies have found that exposure to nanoplastics inhibited hematopoietic function, however, the effect of polystyrene nanoplastics (PSNPs) on the human CD34+ hematopoietic stem/progenitor cells (HSPCs) and its underlying mechanism remains unknown. In this study, the toxic effects were evaluated and the metabolites changes were systematically analyzed using the metabolomics study in combination with multivariate statistical analysis in HSPCs with PSNPs treatment. The results show that PSNPs could be uptake by cells, significantly decrease cell viability and cause cell membrane damage manifested as increased LDH release in cellular supernatant. Besides, the colony formation assay shows that PSNPs exposure can inhibit the proliferation and differentiation of HSPCs. Meanwhile, we found that PSNPs disturbed the metabolic activity, including amino acids, SCFAs, organic acids, fatty acids and carbohydrates, and mainly affect citrate cycle (TCA cycle) metabolism pathway. Those findings are helpful in evaluating the toxicity mechanisms and providing guidance in the selection of potential metabolism-related biomarkers of hematopoietic damage caused by nanoplastics exposure.PMID:37164248 | DOI:10.1016/j.fct.2023.113817

Toxicol Lett. 2023 May 8:S0378-4274(23)00167-4. doi: 10.1016/j.toxlet.2023.04.008. Online ahead of print.ABSTRACTIn long term rodent studies administering Cyclobutrifluram (TYMIRIUM® Technology), a new agrochemical, there was a slight elevation of incidence of hepatocellular carcinomas in male CD-1 mice that was within the historical control range but appeared to be dose responsive. Cyclobutrifluram's ability to activate mouse constitutive androstane receptor (CAR) mediated gene transcription was confirmed in vitro, therefore a 28-day dietary toxicity study was conducted in vivo in male CD-1 mice to assess the CAR activation mode of action hypothesis of Cyclobutrifluram along with phenobarbital, a known CAR activator. In addition to other end points comprehensive (polar and lipidomic) hybrid metabolomics analyses were performed on terminal plasma and liver samples following 2-, 7- and 28-days dietary exposure to cyclobutrifluram and phenobarbital. The data generation and quality assessments were performed in line with the principles of the MEtabolomics standaRds Initiative in Toxicology (MERIT). First the full annotated feature set was used to compare the metabolomic changes induced by the administration of the two test substances using Shared and Unique Structures plots. This gave a comprehensive overview of the similarity of the two effect profiles showing good correlation and demonstrated that no other, alternative effect signatures were detected. Then the phenobarbital induced differentially abundant metabolites were selected, compared to the literature and their direction of change was assessed in cyclobutrifluram profiles, finding good agreement. Both approaches concluded that the metabolomics data supports the CAR activation hypothesis. Comparison of the metabolomic effect profiles can be a line of evidence in mode of action hypothesis testing in the chemical risk assessment process.PMID:37164126 | DOI:10.1016/j.toxlet.2023.04.008

Curr Biol. 2023 Apr 30:S0960-9822(23)00528-6. doi: 10.1016/j.cub.2023.04.046. Online ahead of print.ABSTRACTMost eukaryotes respire oxygen, using it to generate biomass and energy. However, a few organisms have lost the capacity to respire. Understanding how they manage biomass and energy production may illuminate the critical points at which respiration feeds into central carbon metabolism and explain possible routes to its optimization. Here, we use two related fission yeasts, Schizosaccharomyces pombe and Schizosaccharomyces japonicus, as a comparative model system. We show that although S. japonicus does not respire oxygen, unlike S. pombe, it is capable of efficient NADH oxidation, amino acid synthesis, and ATP generation. We probe possible optimization strategies through the use of stable isotope tracing metabolomics, mass isotopologue distribution analysis, genetics, and physiological experiments. S. japonicus appears to have optimized cytosolic NADH oxidation via glycerol-3-phosphate synthesis. It runs a fully bifurcated TCA pathway, sustaining amino acid production. Finally, we propose that it has optimized glycolysis to maintain high ATP/ADP ratio, in part by using the pentose phosphate pathway as a glycolytic shunt, reducing allosteric inhibition of glycolysis and supporting biomass generation. By comparing two related organisms with vastly different metabolic strategies, our work highlights the versatility and plasticity of central carbon metabolism in eukaryotes, illuminating critical adaptations supporting the preferential use of glycolysis over oxidative phosphorylation.PMID:37164017 | DOI:10.1016/j.cub.2023.04.046

J Plant Physiol. 2023 May 5;285:153995. doi: 10.1016/j.jplph.2023.153995. Online ahead of print.ABSTRACTPlant growth-promoting rhizobacteria (PGPR) can promote plant growth and protect plants from pathogens, which contributes to sustainable agricultural development. Several studies have reported their beneficial characteristics in facilitating plant growth and development and enhancing plant stress resistance through different mechanisms. However, there is still a challenge to study the molecular mechanism of plant response to PGPR. We integrated the transcriptome and metabolome of Arabidopsis thaliana (Arabidopsis) to understand its responses to the inoculation with an isolated PGPR strain (BT22) of Bacillus megaterium. Fresh shoot weight, dry shoot weight and leaf number of Arabidopsis were increased by BT22 treatment, showing a positive growth-promoting effect. According multi-omics analysis, 878 differentially expressed genes (296 up-regulated, 582 down-regulated) and 139 differentially expressed metabolites (66 up-regulated, 73 down-regulated) response to BT22 inoculation. GO enrichment results indicate that the up-regulated genes mainly enriched in the regulation of growth and auxin response pathways. In contrast, the down-regulated genes mainly enriched in wounding response, jasmonic acid and ethylene pathways. BT22 inoculation regulated plant hormone signal transduction of Arabidopsis, including auxin and cytokinin response genes AUX/IAA, SAUR, and A-ARR related to cell enlargement and cell division. The contents of nine flavonoids and seven phenylpropanoid metabolites were increased, which help to induce systemic resistance in plants. These results suggest that BT22 promoted Arabidopsis growth by regulating plant hormone homeostasis and inducing metabolome reprogramming.PMID:37163868 | DOI:10.1016/j.jplph.2023.153995

Environ Sci Pollut Res Int. 2023 May 10. doi: 10.1007/s11356-023-27145-4. Online ahead of print.ABSTRACT2,5-Dichloro-1,4-benzenediol (2,5-DCBQ) is a putative disinfection by-product that belongs to the halogenated benzoquinone class. However, its developmental toxicity and related mechanism remained unclarified. In our study, we used zebrafish embryos as the model and exposed them to graded concentrations of 2,5-DCBQ (100, 200, 300, 400 μg/L). We found that the rate of epiboly abnormalities increased significantly in a concentration-dependent manner. The results of whole-mount in situ hybridization (WISH) indicated that the expression patterns and levels of chordin (dorsoventral marker), foxa2 (endodermal marker), eve1 (ventral mesodermal marker), and foxb1a (ectodermal marker) were altered, suggesting that 2,5-DCBQ might affect the germ layer development of zebrafish embryos. Integrated transcriptomic and metabolomic analyses were adopted to explore the molecular mechanisms of embryonic developmental delays. The results showed that 2,5-DCBQ exposure induced 1163 differentially expressed genes (DEGs) and 37 differential metabolites (DEMs). Bioinformatic analysis enriched the most affected molecular pathways (Wnt signaling pathway, cell adhesion molecules, actin cytoskeleton regulation) and metabolic pathways (purine metabolism, aminoacyl-tRNA biosynthesis, arginine and proline metabolism) in zebrafish embryos. To summarize, our findings broadened the molecular mechanisms of 2,5-DCBQ embryotoxicity through multi-omics and bioinformatic analyses.PMID:37165267 | DOI:10.1007/s11356-023-27145-4

Nature. 2023 May 10. doi: 10.1038/s41586-023-05989-7. Online ahead of print.ABSTRACTThe spatiotemporal structure of the human microbiome1,2, proteome3 and metabolome4,5 reflects and determines regional intestinal physiology and may have implications for disease6. Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals7. To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease.PMID:37165188 | DOI:10.1038/s41586-023-05989-7