PubMed
Time of exercise differentially impacts bone growth in mice
Nat Metab. 2024 May 28. doi: 10.1038/s42255-024-01057-0. Online ahead of print.ABSTRACTAlthough physical training has been shown to improve bone mass, the time of day to exercise for optimal bone growth remains uncertain. Here we show that engaging in physical activity during the early active phase, as opposed to the subsequent active or rest phase, results in a more substantial increase in bone length of male and female mice. Transcriptomic and metabolomic methodologies identify that exercise during the early active phase significantly upregulates genes associated with bone development and metabolism. Notably, oxidative phosphorylation-related genes show a rhythmic expression in the chondrification centre, with a peak at the early active phase, when more rhythmic genes in bone metabolism are expressed and bone growth is synergistically promoted by affecting oxidative phosphorylation, which is confirmed by subsequent pharmacological investigations. Finally, we construct a signalling network to predict the impact of exercise on bone growth. Collectively, our research sheds light on the intricacies of human exercise physiology, offering valuable implications for interventions.PMID:38806654 | DOI:10.1038/s42255-024-01057-0
Gut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction
Nat Commun. 2024 May 28;15(1):4155. doi: 10.1038/s41467-024-48355-5.ABSTRACTThe gut microbiome (GM) modulates body weight/composition and gastrointestinal functioning; therefore, approaches targeting resident gut microbes have attracted considerable interest. Intermittent fasting (IF) and protein pacing (P) regimens are effective in facilitating weight loss (WL) and enhancing body composition. However, the interrelationships between IF- and P-induced WL and the GM are unknown. The current randomized controlled study describes distinct fecal microbial and plasma metabolomic signatures between combined IF-P (n = 21) versus a heart-healthy, calorie-restricted (CR, n = 20) diet matched for overall energy intake in free-living human participants (women = 27; men = 14) with overweight/obesity for 8 weeks. Gut symptomatology improves and abundance of Christensenellaceae microbes and circulating cytokines and amino acid metabolites favoring fat oxidation increase with IF-P (p < 0.05), whereas metabolites associated with a longevity-related metabolic pathway increase with CR (p < 0.05). Differences indicate GM and metabolomic factors play a role in WL maintenance and body composition. This novel work provides insight into the GM and metabolomic profile of participants following an IF-P or CR diet and highlights important differences in microbial assembly associated with WL and body composition responsiveness. These data may inform future GM-focused precision nutrition recommendations using larger sample sizes of longer duration. Trial registration, March 6, 2020 (ClinicalTrials.gov as NCT04327141), based on a previous randomized intervention trial.PMID:38806467 | DOI:10.1038/s41467-024-48355-5
The Immune Regulatory Mechanism of Adrenomedullin on Promoting the Proliferation and Differentiation of Dental Pulp Stem Cells
Int Dent J. 2024 May 27:S0020-6539(24)00125-4. doi: 10.1016/j.identj.2024.04.022. Online ahead of print.ABSTRACTOBJECTIVE: This research seeks to analyse the immunomodulatory impacts of adrenomedullin (ADM) on macrophages induced by bacterial lipopolysaccharide and to investigate the influence of macrophage-conditioned media from various stimulating factors on the biological activity of dental pulp stem cells (DPSCs) in vitro.METHODS: The polarisation effect of ADM on macrophages was analysed through cell immunofluorescence staining and flow cytometry. Potential mechanisms were explored through transcriptomics and metabolomics. The impact of different macrophage-conditioned media on the biological activity of DPSCs was evaluated through western blotting, Realtime fluorescence quantitative, alkaline phosphatase activity assay, and eosin red staining. Each experiment was performed with 3 biological and 3 technical duplicate measurements. Statistical analysis was performed with t test and one-way ANOVA, and mathematical significance defined as P < .05.RESULTS: ADM can reverse polarisation of macrophages towards M2 phenotype by Lipopolysaccharide and the conditioned media of ADM-induced M2 polarised macrophages significantly enhances the proliferation and differentiation of DPSCs. The mechanism may involve the metabolic reprogramming of macrophages by ADM, specifically promoting the metabolic shift from glycolysis to mitochondrial oxidative phosphorylation in Lipopolysaccharide-induced macrophages.CONCLUSION: These results indicate that ADM is involved in suppressing inflammation and enhancing the proliferation and differentiation of DPSCs by reprogramming macrophage metabolism.PMID:38806333 | DOI:10.1016/j.identj.2024.04.022
Characterization of CsUGT73AC15 as a Multifunctional Glycosyltransferase Impacting Flavonol Triglycoside Biosynthesis in Tea Plants
J Agric Food Chem. 2024 May 28. doi: 10.1021/acs.jafc.4c03824. Online ahead of print.ABSTRACTFlavonol glycosides, contributing to the health benefits and distinctive flavors of tea (Camellia sinensis), accumulate predominantly as diglycosides and triglycosides in tea leaves. However, the UDP-glycosyltransferases (UGTs) mediating flavonol multiglycosylation remain largely uncharacterized. In this study, we employed an integrated proteomic and metabolomic strategy to identify and characterize key UGTs involved in flavonol triglycoside biosynthesis. The recombinant rCsUGT75AJ1 exhibited flavonoid 4'-O-glucosyltransferase activity, while rCsUGT75L72 preferentially catalyzed 3-OH glucosylation. Notably, rCsUGT73AC15 displayed substrate promiscuity and regioselectivity, enabling glucosylation of rutin at multiple sites and kaempferol 3-O-rutinoside (K3R) at the 7-OH position. Kinetic analysis revealed rCsUGT73AC15's high affinity for rutin (Km = 9.64 μM). Across cultivars, CsUGT73AC15 expression inversely correlated with rutin levels. Moreover, transient CsUGT73AC15 silencing increased rutin and K3R accumulation while decreasing their respective triglycosides in tea plants. This study offers new mechanistic insights into the key roles of UGTs in regulating flavonol triglycosylation in tea plants.PMID:38805380 | DOI:10.1021/acs.jafc.4c03824
Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit
JAMA Netw Open. 2024 May 1;7(5):e2413399. doi: 10.1001/jamanetworkopen.2024.13399.ABSTRACTIMPORTANCE: Disturbances in maternal, placental, and fetal metabolism are associated with developmental outcomes. Associations of maternal, placental, and fetal metabolism with subsequent neurodevelopmental outcomes in the child are understudied.OBJECTIVE: To investigate the metabolic associations within the maternal-placental-fetal unit and subsequent neurodevelopmental outcomes in younger siblings of children with autism spectrum disorder (ASD).DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within a subset of the Markers of Autism Risk in Babies, Learning Early Signs (MARBLES) cohort. MARBLES is a prospective birth cohort of younger siblings of children with ASD assessed for neurodevelopmental outcomes at approximately age 36 months. Participants in MARBLES were recruited through the UC Davis MIND Institute. This subset of the MARBLES cohort included younger siblings born between 2009 and 2015. Maternal third trimester serum, placental tissue, and umbilical cord serum samples were collected from participants. Only pregnancies with at least 2 of these sample types were included in this analysis. Data analysis was conducted from March 1, 2023, to March 15, 2024.EXPOSURES: Quantitative metabolomics analysis was conducted on maternal third trimester serum, as well as placental tissue and umbilical cord serum collected at delivery.MAIN OUTCOMES AND MEASURES: Using the Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning, outcomes were classified as ASD, other nontypical development (non-TD), and typical development (TD).RESULTS: This analysis included 100 maternal serum samples, 141 placental samples, and 124 umbilical cord serum samples from 152 pregnancies (median [IQR] maternal age, 34.6 [30.8-38.3] years; median [IQR] gestational age, 39.0 [38.6-39.7] weeks; 87 [57.2%] male infants). There was no evidence that the maternal third trimester serum metabolome was significantly associated with the other metabolomes. The placental and cord serum metabolomes were highly correlated (first latent variate pair: R2 = 0.75; P < .001) and the variate scores for each tissue were significantly associated with reduced risk of non-TD (placenta: relative risk [RR], 0.13; 95% CI, 0.02-0.71; cord: RR, 0.13; 95% CI, 0.03-0.70) but not ASD (placenta: RR, 1.09; 95% CI, 0.42-2.81; cord: RR, 0.63; 95% CI, 0.23-1.73) compared with the TD reference group.CONCLUSIONS AND RELEVANCE: In this cohort study of children with high familial risk of ASD, placental and cord serum metabolism at delivery were highly correlated. Furthermore, placental and cord serum metabolic profiles were associated with risk of non-TD.PMID:38805224 | DOI:10.1001/jamanetworkopen.2024.13399
The white lupin trehalase gene LaTRE1 regulates cluster root formation and function under phosphorus deficiency
Plant Physiol. 2024 May 28:kiae290. doi: 10.1093/plphys/kiae290. Online ahead of print.ABSTRACTUnder phosphorus (P) deficiency, white lupin (Lupinus albus L.) forms specialized root structure, called cluster root (CR), to improve soil exploration and nutrient acquisition. Sugar signaling is thought to play a vital role in the development of CR. Trehalose and its associated metabolites are the essential sugar signal molecules that link growth and development to carbon metabolism in plants, however, their roles in the control of CR are still unclear. Here, we investigated the function of the trehalose metabolism pathway by pharmacological and genetic manipulation of the activity of trehalase in white lupin, the only enzyme that degrades trehalose into glucose. Under P deficiency, validamycin A treatment, which inhibits trehalase, led to the accumulation of trehalose and promoted the formation of CR with enhanced organic acid production, whereas overexpression of the white lupin TREHALASE1 (LaTRE1) led to decreased trehalose levels, lateral rootlet density, and organic acid production. Transcriptomic and virus-induced gene silencing (VIGS) results revealed that LaTRE1 negatively regulates the formation of CRs, at least partially, by the suppression of LaLBD16, whose putative ortholog in Arabidopsis (Arabidopsis thaliana) acts downstream of ARF7- and ARF19-dependent auxin signaling in lateral root formation. Overall, our findings provide an association between the trehalose metabolism gene LaTRE1 and CR formation and function with respect to organic acid production in white lupin under P deficiency.PMID:38805210 | DOI:10.1093/plphys/kiae290
Comparison of data processing strategies using commercial vs. open-source software in GC-Orbitrap-HRMS untargeted metabolomics analysis for food authentication: thyme geographical differentiation and marker identification as a case study
Anal Bioanal Chem. 2024 May 28. doi: 10.1007/s00216-024-05347-0. Online ahead of print.ABSTRACTUntargeted analysis of gas chromatography-high-resolution mass spectrometry (GC-HRMS) data is a key and time-consuming challenge for identifying metabolite markers in food authentication applications. Few studies have been performed to evaluate the capability of untargeted data processing tools for feature extraction, metabolite annotation, and marker selection from untargeted GC-HRMS data since most of them are focused on liquid chromatography (LC) analysis. In this framework, this study provides a comprehensive evaluation of data analysis tools for GC-Orbitrap-HRMS plant metabolomics data, including the open-source MS-DIAL software and commercial Compound Discoverer™ software (designed for Orbitrap data processing), applied for the geographical discrimination and search for thyme markers (Spanish vs. Polish differentiation) as the case study. Both approaches showed that the feature detection process is highly affected by unknown metabolites (Levels 4-5 of identification confidence), background signals, and duplicate features that must be carefully assessed before further multivariate data analysis for reliable putative identification of markers. As a result, Compound Discoverer™ and MS-DIAL putatively annotated 52 and 115 compounds at Level 2, respectively. Further multivariate data analysis allowed the identification of differential compounds, showing that the putative identification of markers, especially in challenging untargeted analysis, heavily depends on the data processing parameters, including available databases used during compound annotation. Overall, this method comparison pointed out both approaches as good options for untargeted analysis of GC-Orbitrap-HRMS data, and it is presented as a useful guide for users to implement these data processing approaches in food authenticity applications depending on their availability.PMID:38805060 | DOI:10.1007/s00216-024-05347-0
AntDAS-GCMS: A New Comprehensive Data Analysis Platform for GC-MS-Based Untargeted Metabolomics with the Advantage of Addressing the Time Shift Problem
Anal Chem. 2024 May 28. doi: 10.1021/acs.analchem.4c00100. Online ahead of print.ABSTRACTOver the years, a number of state-of-the-art data analysis tools have been developed to provide a comprehensive analysis of data collected from gas chromatography-mass spectrometry (GC-MS). Unfortunately, the time shift problem remains unsolved in these tools. Here, we developed a novel comprehensive data analysis strategy for GC-MS-based untargeted metabolomics (AntDAS-GCMS) to perform total ion chromatogram peak detection, peak resolution, time shift correction, component registration, statistical analysis, and compound identification. Time shift correction was specifically optimized in this work. The information on mass spectra and elution profiles of compounds was used to search for inherent landmarks within analyzed samples to resolve the time shift problem across samples efficiently and accurately. The performance of our AntDAS-GCMS was comprehensively investigated by using four complex GC-MS data sets with various types of time shift problems. Meanwhile, AntDAS-GCMS was compared with advanced GC-MS data analysis tools and classic time shift correction methods. Results indicated that AntDAS-GCMS could achieve the best performance compared to the other methods.PMID:38805056 | DOI:10.1021/acs.analchem.4c00100
Fluorescence Lifetime Imaging of Lipid Heterogeneity in the Inner Mitochondrial Membrane with a Super-photostable Environment-Sensitive Probe
Angew Chem Int Ed Engl. 2024 May 28:e202404328. doi: 10.1002/anie.202404328. Online ahead of print.ABSTRACTThe inner mitochondrial membrane (IMM) undergoes dynamic morphological changes, which are crucial for the maintenance of mitochondrial functions as well as cell survival. As the dynamics of the membrane are governed by its lipid components, a fluorescent probe that can sense spatiotemporal alterations in the lipid properties of the IMM over long periods of time is required to understand mitochondrial physiological functions in detail. Herein, we report a red-emissive IMM-labeling reagent with excellent photostability and sensitivity to its environment, which enables the visualization of the IMM ultrastructure using super-resolution microscopy as well as of the lipid heterogeneity based on the fluorescence lifetime at the single mitochondrion level. Combining the probe and fluorescence lifetime imaging microscopy (FLIM) showed that peroxidation of unsaturated lipids in the IMM by reactive oxygen species caused an increase in the membrane order, which took place prior to mitochondrial swelling.PMID:38804831 | DOI:10.1002/anie.202404328
Foliar applications of a Malvaceae-derived protein hydrolysate and its fractions differentially modulate yield and functional traits of tomato under optimal and suboptimal nitrogen application
J Sci Food Agric. 2024 May 28. doi: 10.1002/jsfa.13596. Online ahead of print.ABSTRACTBACKGROUND: Protein hydrolysates (PHs) can enhance plant nitrogen nutrition and improve the quality of vegetables, depending on their bioactive compounds. A tomato greenhouse experiment was conducted under both optimal (14 mM) and suboptimal (2 mM) nitrogen (N-NO3) conditions. Tomatoes were treated with a new Malvaceae-derived PH (MDPH) and its molecular fractions (MDPH1, >10 kDa; MDPH2, 1-10 kDa and MDPH3, <1 kDa).RESULTS: Under optimal N conditions, the plants increased biomass and fruit yield, and showed a higher photosynthetic pigment content in leaves in comparison with suboptimal N, whereas under N-limiting conditions, an increase in dry matter, soluble solid content (SSC) and lycopene, a reduction in firmness, and changes in organic acid and phenolic compounds were observed. With 14 mM N-NO3, MDPH3 stimulated an increase in dry weight and increased yield components and lycopene in the fruit. The MDPH2 fraction also resulted in increased lycopene accumulation in fruit under 14 mM N-NO3. At a low N level, the PH fractions showed distinct effects compared with the whole MDPH and the control, with an increase in biomass for MDPH1 and MDPH2 and a higher pigment content for MDPH3. Regardless of N availability, all the fractions affected fruit quality by increasing SSC, whereas MDPH2 and MDPH3 modified organic acid content and showed a higher concentration of flavonols, lignans, and stilbenes.CONCLUSION: The molecular weight of the peptides modifies the effect of PHs on plant performance, with different behavior depending on the level of N fertilization, confirming the effectiveness of fractioning processes. © 2024 Society of Chemical Industry.PMID:38804737 | DOI:10.1002/jsfa.13596
Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma
Clin Transl Med. 2024 Jun;14(6):e1727. doi: 10.1002/ctm2.1727.ABSTRACTBACKGROUND: The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC.METHODS: A high throughput liquid chromatography-tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment-resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient-derived organoid (PDO) assays.RESULTS: A multiomics profiling of 8536 high-confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment-resolved classification were divided into three subtypes. The C1 subtype showed enrichment in ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5-lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively.CONCLUSION: Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.PMID:38804617 | DOI:10.1002/ctm2.1727
Combining metabolomics and transcriptomics to reveal the potential medicinal value of rare species Glycyrrhiza squamulose
Heliyon. 2024 May 10;10(10):e30868. doi: 10.1016/j.heliyon.2024.e30868. eCollection 2024 May 30.ABSTRACTLicorice is a well-known Chinese medicinal plant that is widely used to treat multiple diseases and process food; however, wild licorice is now facing depletion. Therefore, there is an urgent need to identify and protect licorice germplasm diversity. In this study, metabolomic and transcriptomic analyses were conducted to investigate the biodiversity and potential medicinal value of the rare wild Glycyrrhiza squamulose. A total of 182 differentially accumulated metabolites and 395 differentially expressed genes were identified by comparing Glycyrrhiza uralensis and Glycyrrhiza squamulose. The molecular weights of the chemical component of G. squamulose were comparable with those of G. uralensis, suggesting that G. squamulose may have medicinal value. Differentially accumulated metabolites (DAMs), mainly flavonoids such as kaempferol-3-O-galactoside, kaempferol-3-O-(6"malonyl) glucoside, and hispidulin-7-O-glucoside, showed potential vitality in G. squamulose. Comparative transcriptomics with G. uralensis showed that among the 395 differentially expressed genes (DEGs), 69 were enriched in the isoflavonoid biosynthesis pathway. Multiomics analysis showed that the distinction in flavonoid biosynthesis between G. squamulose and G. uralensis was strongly associated with the expression levels of IF7GT and CYP93C. In addition to identifying similarities and differences between G. squamulose and G. uralensis, this study provides a theoretical basis to protect and investigate rare species such as G. squamulose.PMID:38803917 | PMC:PMC11128877 | DOI:10.1016/j.heliyon.2024.e30868
<em>gys1</em> regulates maternal glycogen reserve essential for embryonic development in zebrafish
Heliyon. 2024 May 14;10(10):e31149. doi: 10.1016/j.heliyon.2024.e31149. eCollection 2024 May 30.ABSTRACTThe reserve of glycogen is essential for embryonic development. In oviparous fish, egg is an isolated system after egg laying with all the required energy deposits by their mothers. However, the key regulated factor mediates the storage of maternal glycogen reserve which support for embryogenesis in the offspring is largely unknown. Glycogen synthase (GYS) is a central enzyme for glycogen synthesis. In our previous study, we generated a gys1 knockout zebrafish line, showed an embryonic developmental defect in F3 generation. In this study, firstly we determined that the gys1 was maternal origin by backcrossing the F2 mutant with wildtype lines. PAS staining and glycogen content measurement showed that glycogen reserve was reduced both in ovaries and embryos in the mutant group compared to wildtypes. Free glucose measurement analysis showed a 50 % of reduction in gys1 mutant embryos compared to wildtype embryos at 24 hpf; showed an approximal 50 % of reduction in gys1 mutant adults compared to wildtypes. Microinjection of 2-NBDG in embryos and comparison of fluorescent signal demonstrated that glucose uptake ability was decreased in the mutant embryos, indicating an impaired glucose metabolism. Untargeted metabolomics analysis then was employed and revealed that key modified metabolites enriched into vitamin B pathway, carbohydrate and unsaturated fatty acid pathways. These results demonstrated that gys1 played a role on glycogen metabolism, involved into the maternal glycogen reserve which essentially contribute to embryonic development.PMID:38803914 | PMC:PMC11128933 | DOI:10.1016/j.heliyon.2024.e31149
Exploring the impact of irradiation on the sensory quality of pork based on a metabolomics approach
Food Chem X. 2024 May 14;22:101460. doi: 10.1016/j.fochx.2024.101460. eCollection 2024 Jun 30.ABSTRACTThe effects of irradiation on pork quality characteristics were investigated by combining sensory experiments, pork color, TBARS, volatile components, and differential metabolites. Pork irradiated at a dose of 1 kGy received the highest sensory scores, whereas pork irradiated at doses of 3 and 5 kGy obtained lower sensory scores, particularly with regard to odor. Irradiation makes pork more ruddy and promotes fat oxidation, leading to increased a* and TBARS values. The main volatile substances in irradiated pork were hydrocarbons, aldehydes, and alcohols, and hexanal, heptanal, and valeric acid were considered as important substances responsible for the generation of radiation-induced off-flavors. 65 differential metabolites were identified. l-pyroglutamic acid, l-glutamate, l-proline, fumarate acids, betaine, and l-anserine were considered as the main substances contributing to the differences in pork quality. In addition, metabolic pathways such as arginine biosynthesis, alanine, aspartate and glutamate metabolism were found to be considerably affected by irradiation.PMID:38803672 | PMC:PMC11129168 | DOI:10.1016/j.fochx.2024.101460
Drought stress tolerance and metabolomics of Medicago sativa induced by Bacillus amyloliquefaciens DGL1
Front Plant Sci. 2024 May 13;15:1378707. doi: 10.3389/fpls.2024.1378707. eCollection 2024.ABSTRACTINTRODUCTION: This study used Bacillus amyloliquefaciens DGL1 isolated from the arid sandy land of the Qinghai-Tibetan Plateau as the research strain and investigated the effects of DGL1 on the biomass, physiology, and metabolites of Medicago sativa under different intensities of drought stress to provide a high-quality bacterial source and a theoretical basis for the research and development of biological fertilizer suitable for arid areas.METHODS: The exopolysaccharides (EPS), 1-Aminocyclopropane-1-carboxylate deaminase (ACC), and phosphorus solubilizing capacity of DGL1 were determined. The effects of a DGL1 suspension on alfalfa biomass, physiological indexes, degree of peroxidation of cell membranes, and activity of antioxidant enzymes were determined after irrigating roots under drought stress. The effects on soil physicochemical properties were also evaluated, and metabolomics analysis was performed to explore the effect of DGL1 on the metabolites of alfalfa under drought stress.RESULTS: Strain DGL1 produced extracellular polysaccharide EPS and ACC deaminase and was capable of phosphorus solubilization. Treatment with DGL1 increased the biomass of alfalfa under different degrees of drought stress, significantly increased the activities of alfalfa antioxidant enzymes Super Oxide Dismutase (SOD), Peroxidase (POD), and catalase (CAT), reduced the content of MDA and H2O2, and increased the content of quick-acting phosphorus, quick-acting potassium, ammonium nitrogen, and nitrate nitrogen in the soil, thus improving soil fertility. Through metabolomics analysis, DGL1 was shown to affect amino acid metabolic pathways, such as arginine, leucine, glutamate, and tyrosine, as well as the levels of energy-providing polysaccharides and lipids, in alfalfa under 15% PEG-6000 drought stress, enhancing alfalfa's capacity to resist drought stress.DISCUSSION: Strain DGL1 enhances the drought suitability of alfalfa and has the potential for dryland development as a biological agent.PMID:38803604 | PMC:PMC11128672 | DOI:10.3389/fpls.2024.1378707
Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis
Front Nutr. 2024 May 13;11:1379390. doi: 10.3389/fnut.2024.1379390. eCollection 2024.ABSTRACTINTRODUCTION: The branched-chain amino acids (BCAAs) are essential to mammalian growth and development but aberrantly elevated in obesity and diabetes. Each BCAA has an independent and specific physio-biochemical effect on the host. However, the exact molecular mechanism of the detrimental effect of valine on metabolic health remains largely unknown.METHODS AND RESULTS: This study showed that for lean mice treated with valine, the hepatic lipid metabolism and adipogenesis were enhanced, and the villus height and crypt depth of the ileum were significantly increased. Transcriptome profiling on white and brown adipose tissues revealed that valine disturbed multiple signaling pathways (e.g., inflammation and fatty acid metabolism). Integrative cecal metagenome and metabolome analyses found that abundances of Bacteroidetes decreased, but Proteobacteria and Helicobacter increased, respectively; and 87 differential metabolites were enriched in several molecular pathways (e.g., inflammation and lipid and bile acid metabolism). Furthermore, abundances of two metabolites (stercobilin and 3-IAA), proteins (AMPK/pAMPK and SCD1), and inflammation and adipogenesis-related genes were validated.DISCUSSION: Valine treatment affects the intestinal microbiota and metabolite compositions, induces gut inflammation, and aggravates hepatic lipid deposition and adipogenesis. Our findings provide novel insights into and resources for further exploring the molecular mechanism and biological function of valine on lipid metabolism.PMID:38803448 | PMC:PMC11128663 | DOI:10.3389/fnut.2024.1379390
The gut metabolome in a cohort of pregnant and lactating women from Antioquia-Colombia
Front Mol Biosci. 2024 May 13;11:1250413. doi: 10.3389/fmolb.2024.1250413. eCollection 2024.ABSTRACTNutrition during the perinatal period is an essential component of health and one that can severely impact the correct development of a human being and its overall condition, in all the subsequent stages of life. The availability of several compounds, mainly macronutrients and micronutrients, plays a key role in the balanced nutrition of both mother and baby and is a process with direct relation to the gut microbiome. Thus, we hereby refer to the set of small molecules derived from gut microbiome metabolism as the gut metabolome. These continuous processes occurring in the gut of a gestating or lactating mother related to microbial communities and nutrients, can be revealed by metabolomics. In this study, we explore for the first time the gut metabolome of pregnant and lactating women, from our region of Antioquia-Colombia, applying untargeted metabolomics by LC-QTOF-MS, and molecular networking. Regarding the gut metabolome composition of the cohort, we found, key metabolites that can be used as biomarkers of microbiome function, overall metabolic health, dietary intake, pharmacology, and lifestyle. In our cohort, pregnant women evidenced a significantly higher abundance of prostaglandins, alkaloids, corticosteroids, organosilicons, and natural toxins, while in lactating women, lipids stand out. Our results suggest that unveiling the metabolic phenotype of the gut microbiome of an individual, by untargeted metabolomics, allows a broad visualization of the chemical space present in this important niche and enables the recognition of influential indicators of the host's health status and habits, especially of women during this significant perinatal period. This study constitutes the first evidence of the use of untargeted LC-QTOF-MS coupled with molecular networking analysis, of the gut microbiome in a Colombian cohort and establishes a methodology for finding relative abundances of key metabolites, with potential use in nutritional and physiological state assessments, for future personalized health and nutrition practices.PMID:38803424 | PMC:PMC11128665 | DOI:10.3389/fmolb.2024.1250413
Metagenomic and metabolomic analyses reveal differences in rumen microbiota between grass- and grain-fed Sanhe heifers
Front Microbiol. 2024 May 13;15:1336278. doi: 10.3389/fmicb.2024.1336278. eCollection 2024.ABSTRACTINTRODUCTION: The aim of this study was to investigate the effects of diets on the composition and function of rumen microbiome and metabolites in Sanhe heifers.METHODS: Metagenomic and metabolomic analyses were performed using rumen fluid samples collected from Sanhe heifers (n = 20) with similar body weights and ages from grass-fed and grain-fed systems.RESULTS: The grain-fed group exhibited more intensive rumen fermentation than the grass-fed group. However, the grass-fed group exhibited carbohydrate metabolism and methane production higher than that of the grain-fed group; these increases were observed as a higher abundance of various bacterial phyla (Firmicutes, Bacteroidetes, Actinobacteria, Lentisphaerae, and Verrucomicrobia), families (Lachnospiraceae, Eubacteriaceae, and Eggerthellaceae), and the archaeal family Methanobacteriaceae. A comparison of genes encoding carbohydrate-active enzymes, using Kyoto Encyclopedia of Genes and Genome profiles, revealed noteworthy differences in the functions of rumen microbiota; these differences were largely dependent on the feeding system.CONCLUSION: These results could help manipulate and regulate feed efficiency in Sanhe cattle.PMID:38803375 | PMC:PMC11128563 | DOI:10.3389/fmicb.2024.1336278
Transcriptomic and metabolomic correlation analysis: effect of initial SO(2) addition on higher alcohol synthesis in Saccharomyces cerevisiae and identification of key regulatory genes
Front Microbiol. 2024 May 13;15:1394880. doi: 10.3389/fmicb.2024.1394880. eCollection 2024.ABSTRACTINTRODUCTION: Higher alcohols are volatile compounds produced during alcoholic fermentation that affect the quality and safety of the final product. This study used a correlation analysis of transcriptomics and metabolomics to study the impact of the initial addition of SO2 (30, 60, and 90 mg/L) on the synthesis of higher alcohols in Saccharomyces cerevisiae EC1118a and to identify key genes and metabolic pathways involved in their metabolism.METHODS: Transcriptomics and metabolomics correlation analyses were performed and differentially expressed genes (DEGs) and differential metabolites were identified. Single-gene knockouts for targeting genes of important pathways were generated to study the roles of key genes involved in the regulation of higher alcohol production.RESULTS: We found that, as the SO2 concentration increased, the production of total higher alcohols showed an overall trend of first increasing and then decreasing. Multi-omics correlation analysis revealed that the addition of SO2 affected carbon metabolism (ko01200), pyruvate metabolism (ko00620), glycolysis/gluconeogenesis (ko00010), the pentose phosphate pathway (ko00030), and other metabolic pathways, thereby changing the precursor substances. The availability of SO2 indirectly affects the formation of higher alcohols. In addition, excessive SO2 affected the growth of the strain, leading to the emergence of a lag phase. We screened the ten most likely genes and constructed recombinant strains to evaluate the impact of each gene on the formation of higher alcohols. The results showed that ADH4, SER33, and GDH2 are important genes of alcohol metabolism in S. cerevisiae. The isoamyl alcohol content of the EC1118a-ADH4 strain decreased by 21.003%; The isobutanol content of the EC1118a-SER33 strain was reduced by 71.346%; and the 2-phenylethanol content of EC1118a-GDH2 strain was reduced by 25.198%.CONCLUSION: This study lays a theoretical foundation for investigating the mechanism of initial addition of SO2 in the synthesis of higher alcohols in S. cerevisiae, uncovering DEGs and key metabolic pathways related to the synthesis of higher alcohols, and provides guidance for regulating these mechanisms.PMID:38803372 | PMC:PMC11128613 | DOI:10.3389/fmicb.2024.1394880
Overview of the Metabolite Composition and Antioxidant Capacity of Seven Major and Minor Cereal Crops and Their Milling Fractions
J Agric Food Chem. 2024 May 28. doi: 10.1021/acs.jafc.4c01312. Online ahead of print.ABSTRACTCereal grains play an important role in human health as a source of macro- and micronutrients, besides phytochemicals. The metabolite diversity was investigated in cereal crops and their milling fractions by untargeted metabolomics ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) of 69 samples: 7 species (barley, oat, pearl millet, rye, sorghum, triticale, and wheat), 23 genotypes, and 4 milling fractions (husk, bran, flour, and wholegrain). Samples were also analyzed by in vitro antioxidant activity. UHPLC-MS/MS signals were processed using XCMS, and metabolite annotation was based on SIRIUS and GNPS libraries. Bran and husk showed the highest antioxidant capacity and phenolic content/diversity. The major metabolite classes were phenolic acids, flavonoids, fatty acyls, and organic acids. Sorghum, millet, barley, and oats showed distinct metabolite profiles, especially related to the bran fraction. Molecular networking and chemometrics provided a comprehensive insight into the metabolic profiling of cereal crops, unveiling the potential of coproducts and super cereals such as sorghum and millet as sources of polyphenols.PMID:38803291 | DOI:10.1021/acs.jafc.4c01312