Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Exploring the antibiotic resistance of <em>Listeria monocytogenes</em> in food environments - a review

Tue, 15/10/2024 - 12:00
Crit Rev Microbiol. 2024 Oct 15:1-24. doi: 10.1080/1040841X.2024.2412007. Online ahead of print.ABSTRACTListeria monocytogenes, a resilient bacterium in diverse food conditions, such as refrigeration, reduced water activity and low pH, poses a significant threat to the food industry and public health. In recent years, it has been documented an increase in the antibiotic resistance of zoonotic pathogens, including L. monocytogenes. This review provides new insight into the molecular mechanisms involved in both intrinsic and acquired antibiotic resistance of L. monocytogenes with an emphasis on the effect of different environmental and food-related factors. It also explores the relationship of these resistance mechanisms with virulence factors. An analysis of literature data (2009-2021) was conducted to investigate statistically and graphically potential associations between specific antibiotic resistance patterns in the pathogen and food categories using an unbiased variance analysis. The results evidenced that food type had an influence on the antibiotic resistance profiles of L. monocytogenes, with meat and vegetables being the food categories exhibiting the most prevalent profiles. The frequent detection of resistance to ampicillin, penicillin, and tetracycline (non-intrinsic resistances) indicates that specific processing conditions along the food chain may induce them. Many questions remain about the impact of food chain factors (e.g. thermal treatments, cold chain, preservatives, etc.) and food type (low pH, reduced water activity, etc.) on the antibiotic resistance patterns of the pathogen, particularly concerning food-related sources, the resistance mechanisms involved (e.g. cross-protection, horizontal gene transfer, etc.), and the evolutionary processes of antibiotic-resistant microbial populations. Metagenomics, in addition to other -omics technologies (metabolomics and transcriptomics), allows a better understanding of the processes involved in the acquisition of resistance.PMID:39404832 | DOI:10.1080/1040841X.2024.2412007

Gut microbiota carbon and sulfur metabolisms support Salmonella infections

Tue, 15/10/2024 - 12:00
ISME J. 2024 Oct 15:wrae187. doi: 10.1093/ismejo/wrae187. Online ahead of print.ABSTRACTSalmonella enterica serovar Typhimurium is a pervasive enteric pathogen and ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, we performed multi-omics on fecal microbial communities from untreated and Salmonella-infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. These data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella-induced inflammation significantly reduced the diversity of genomes that recruited transcripts in the gut microbiome, yet increased transcript mapping was observed for 7 members, among which Luxibacter and Ligilactobacillus transcript read recruitment was most prevalent. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst members with detected transcript recruitment. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that supports Salmonella respiration. This research advances physiological microbiome insights beyond prior amplicon-based approaches, with the transcriptionally active organismal and metabolic pathways outlined here offering intriguing intervention targets in the Salmonella-infected intestine.PMID:39404095 | DOI:10.1093/ismejo/wrae187

Calycosin-7-O-β-D-Glucoside Ameliorates Palmitate-Induced Lipid Accumulation in HT22 Cells

Tue, 15/10/2024 - 12:00
Actas Esp Psiquiatr. 2024 Oct;52(5):641-652. doi: 10.62641/aep.v52i5.1723.ABSTRACTBACKGROUND: The pathogenesis of Alzheimer's disease (AD) is complex. Recent research suggests that AD patients have early disorders in brain cholesterol metabolism. Cholesterol and its derivatives accumulate in neurons, leading to p-Tau overproduction and synaptic dysfunction, initiating AD progression. Calycosin-7-O-β-D-glucoside (CG), a distinctive constituent of Astragali Radix, holds a representative position. Many clinical trials have demonstrated that CG can attenuate cerebral ischemia/reperfusion injury and preserve the structural integrity of the blood-brain barrier. However, whether CG alleviates tau-mediated neurodegeneration by increasing cholesterol efflux after lipid accumulation remains unexplored.METHODS: Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and multivariate data analysis were employed to investigate metabolic changes in HT22 cells induced by sodium palmitate following 24 hours of CG treatment. The potential therapeutic mechanisms of CG on AD were further examined through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.RESULTS: Metabolomic analysis characterized 24 potential biomarkers, revealing that CG could ameliorate cholesterol metabolic pathways. The results of cell experiments revealed that CG can increase the expression of enzyme cholesterol 24-hydroxylase (CYP46A1) (p < 0.05) and the level of 24 hydroxycholesterol (24-OHC) (p < 0.05), reduce the expression of p-Tau (Thr231)/Tau (p < 0.01), inhibit the formation of lipid droplets.CONCLUSION: CG may inhibit the accumulation of cholesterol and its derivatives in neurons by affecting the CYP46A1-CE-Tau axis, offering a potential therapeutic strategy for AD.PMID:39403908 | DOI:10.62641/aep.v52i5.1723

Causal relationship between plasma lipidome and four types of pancreatitis: a bidirectional Mendelian randomization study

Tue, 15/10/2024 - 12:00
Front Endocrinol (Lausanne). 2024 Sep 30;15:1415474. doi: 10.3389/fendo.2024.1415474. eCollection 2024.ABSTRACTBACKGROUND: Pancreatitis is a serious and complex inflammatory disease that imposes a severe effect on quality of life. Links between plasma lipidome and pancreatitis have been reported, some of which have not yet been clearly elucidated.METHODS: Therefore, our study aimed to investigate the causal relationships between plasma lipidome and four types of pancreatitis by conducting a bidirectional, two-sample Mendelian randomization (MR) analysis. We obtained genetic variants associated with 179 lipid species from a Genome-wide association analysis of plasma lipidome. The aggregated statistical data of acute pancreatitis (AP), alcohol-induced acute pancreatitis (AAP), chronic pancreatitis (CP), and alcohol-induced chronic pancreatitis (ACP) from the FinnGen consortium were exploited as the outcome. The inverse variance weighted (IVW) technique as the main method was used for MR analysis and sensitivity analyses were used to evaluate heterogeneity and pleiotropy.RESULTS: After FDR correction, SE (27:1/20:4) (OR = 0.938, 95%CI = 0.906-0.972, P = 4.38 × 10-4, PFDR = 0.039) was identified to be significantly associated with AP risk. Eight lipid species were identified to be significantly associated with CP risk: SE (27:1/20:4) (OR = 0.911, 95%CI = 0.869-0.954, P = 8.89 × 10-5, PFDR = 0.016), LPC (20:4) (OR = 0.892, 95%CI = 0.843-0.945, P = 9.74 × 10-5, PFDR = 0.009), PC (16:0_22:5) (OR = 0.880, 95%CI = 0.818-0.947, P = 6.29 × 10-4, PFDR = 0.028), PC (17:0_20:4) (OR = 0.893, 95%CI = 0.842-0.948, P = 1.76 × 10-4, PFDR = 0.010), PC (18:0_20:4) (OR = 0.920, 95%CI = 0.874-0.969, P = 1.70 × 10-3, PFDR = 0.038), PC (O-16:0/20:4) (OR = 0.871, 95%CI = 0.804-0.943, P = 6.95 × 10-4, PFDR = 0.025), PC (O-16:1/20:4) (OR = 0.890, 95%CI = 0.832-0.953, P = 7.85 × 10-4, PFDR = 0.023), and PE (O-18:1/20:4) (OR = 0.866, 95%CI = 0.791-0.947, P = 1.61 × 10-3, PFDR = 0.041). Furthermore, genetically predicted increased LPC (20:4) (OR = 0.862, 95%CI = 0.796-0.934, P = 3.00 × 10-4, PFDR = 0.027) and SM (34:2;O2) (OR = 0.753, 95%CI = 0.659-0.860, P = 2.97 × 10-5, PFDR = 0.005) levels were associated with decreased risk of ACP.CONCLUSIONS: Our findings provide evidence of causal associations between the specific types of lipidome and pancreatitis, offering new insights into future clinical research.PMID:39403583 | PMC:PMC11471641 | DOI:10.3389/fendo.2024.1415474

Regulation of glucose metabolism: Effects on oocyte, preimplantation embryo, assisted reproductive technology and embryonic stem cell

Tue, 15/10/2024 - 12:00
Heliyon. 2024 Sep 28;10(19):e38551. doi: 10.1016/j.heliyon.2024.e38551. eCollection 2024 Oct 15.ABSTRACTGlucose is a major energy substrate for cellular life activities, and its metabolic pathways include glycolysis, the pentose phosphate pathway, the hexosamine biosynthesis pathway, and the polyol pathway. Here, we review the glucose uptake pathways, metabolic characteristics, glucose transport, glucose metabolism-related enzymes, and biological importance in mammalian oocyte maturation, early embryo development, and embryonic stem cell proliferation and differentiation. Moreover, the interrelationships among glucose metabolism, female reproduction-related diseases and assisted reproductive technologies are focused. In addition, we review a number of analytical methodologies with the intention to integrate a multi-tiered strategy that encompasses cutting-edge metabolomics, artificial intelligence, epigenetics, and morphological assessments, setting the stage for a pivotal approach to cultivating high-caliber embryos in the future.PMID:39403464 | PMC:PMC11471579 | DOI:10.1016/j.heliyon.2024.e38551

Based on electronic nose and multi-omics, investigate the dynamic changes of volatile and non-volatile organic compounds in waxy wheat Baijiu from different years

Tue, 15/10/2024 - 12:00
Food Chem X. 2024 Sep 28;24:101864. doi: 10.1016/j.fochx.2024.101864. eCollection 2024 Dec 30.ABSTRACTChinese baijiu is highly regarded for its unique flavor, and a variety of crops can be utilized as raw materials in its production. Waxy crops are essential ingredients in the brewing of high-quality baijiu; however, there is currently no comprehensive identification of volatile organic compounds (VOCs) and non-volatile compounds (N-VOCs) in waxy wheat baijiu (WWB). This study aims to investigate the dynamic changes of VOCs and N-VOCs in WWB during several important time periods from new to aged. A total of 25 amino acids underwent changes in the samples, with numerous physiologically active beneficial amino acids showing significant accumulation after aging. Additionally, 517 VOCs changed after aging, predominantly comprising esters and terpenoids, with 72 major VOCs being identified. A total of 718 metabolites were identified in the metabolome, primarily comprising alterations in lipids, amino acids, phenolic acids, organic acids, and alkaloids. These metabolites significantly influenced the levels of amino acids and VOCs. Our study is the first to provide a comprehensive examination of these aspects of WWB, highlighting its unique advantages over other crops. We believe that this research will establish a theoretical foundation for the application of waxy wheat in the baijiu industry, improve baijiu quality, and promote the development of functional baijius.PMID:39403296 | PMC:PMC11471596 | DOI:10.1016/j.fochx.2024.101864

Metabolomic analysis of the impact of red ginseng on equine physiology

Tue, 15/10/2024 - 12:00
Front Vet Sci. 2024 Sep 30;11:1425089. doi: 10.3389/fvets.2024.1425089. eCollection 2024.ABSTRACTINTRODUCTION: Red ginseng (RG), a traditional herbal remedy, has garnered attention owing to its diverse health benefits resulting from its complex composition. However, extensive research is needed to substantiate the efficacy of RG and understand the underlying mechanisms supporting these benefits. This study aimed to identify potential biomarkers and investigate the impact of RG on related metabolic pathways in horse plasma using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics.METHODS: Ten horses were divided into control and RG groups, with the latter administered RG at a dose of 600 mg⋅kg-1⋅day-1 for 3 weeks. Subsequently, the plasma samples were collected and analyzed using LC-MS. Multivariate statistical analysis, volcano plots, and feature-based molecular networking were employed.RESULTS: The analysis identified 16 metabolites that substantially decreased and 21 metabolites that substantially increased following RG consumption. Among the identified metabolites were oleanolic acid, ursolic acid, and ginsenoside Rb1, which are known for their antioxidant and anti-inflammatory properties, as well as lipid species that influence sphingolipid and glycerophospholipid metabolism. Additionally, potential biomarkers, including major RG components, demonstrated distinct group clustering in principal component analysis and partial least squares-discriminant analysis, indicating their utility in assessing the physiological effects of RG consumption.DISCUSSION: This study contributes to a comprehensive understanding of the effects of RG on health.PMID:39403214 | PMC:PMC11471734 | DOI:10.3389/fvets.2024.1425089

Aqueous Extract of Rhubarb Promotes Hepatotoxicity via Facilitating PKM2-Mediated Aerobic Glycolysis in a Rat Model of Diethylnitrosamine-Induced Liver Cancer

Tue, 15/10/2024 - 12:00
Drug Des Devel Ther. 2024 Oct 9;18:4497-4510. doi: 10.2147/DDDT.S476273. eCollection 2024.ABSTRACTOBJECTIVE: To identify the polar parts in Rhubarb that cause hepatotoxicity and explore the underlying mechanisms.METHODS: The rat model of liver cancer was established by gavage of diethylnitrosamine (DEN; 0.002 g/rat) for 14 weeks. Starting from the 11th week, Rhubarb granule (4 g/kg), aqueous, ethyl acetate and n-butanol extract of Rhubarb or Rhein equivalent to a dose of 4 g/kg Rhubarb granule were administered intragastrically for 4 consecutive weeks. Liver tissues from rats treated with DEN and Rhubarb granules were used for non-targeted metabolomics analysis. The correlation between pyruvate kinase isozyme type M2 (PKM2) expression level and the progress and prognosis of hepatocellular carcinoma (HCC) was evaluated through bioinformatics analysis based on TCGA database. Liver tissues and blood samples from rats treated with DEN and aqueous, ethyl acetate and n-butanol extract of Rhubarb were used for the screening of hepatotoxic polar parts of Rhubarb. The liver injuries were evaluated by the changes in pathology, liver function, and the expression levels of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta1 (TGF-β1). The mechanism studies focus on PKM2 expression, and the metabolic reprogramming via detecting the activities of lactate dehydrogenase A (LDHA) and isocitrate dehydrogenase (ICDH). Furthermore, molecular docking analysis was performed to validate the target interaction between Rhein and PKM2, and the hepatotoxicity of Rhein was evaluated by testing liver function in the DEN-induced liver cancer model.RESULTS: The non-targeted metabolomics analysis revealed that Rhubarb promoted aerobic glycolysis in the rat model of DEN-induced liver cancer. And bioinformatics analysis revealed that high PKM2 expression was closely related to the progression and poor prognosis of HCC. In vivo studies indicated that the aqueous extract of Rhubarb, but not ethyl acetate and n-butanol extract, promoted the liver injuries induced by DEN. The mechanism study showed that the aqueous extract of Rhubarb increased the expression of PKM2 and promoted aerobic glycolysis. Moreover, Rhein had a strong binding affinity for PKM2 and aggravated liver injury in the DEN-induced liver cancer model.CONCLUSION: Aqueous extract of Rhubarb promoted hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in the rat model of DEN-induced liver cancer.PMID:39403095 | PMC:PMC11471889 | DOI:10.2147/DDDT.S476273

Itaconate induces tolerance of <em>Staphylococcus aureus</em> to aminoglycoside antibiotics

Tue, 15/10/2024 - 12:00
Front Microbiol. 2024 Sep 30;15:1450085. doi: 10.3389/fmicb.2024.1450085. eCollection 2024.ABSTRACTINTRODUCTION: Staphylococcus aureus is one of the chief pathogens that cause chronic and recurrent infections. Failure of the antibiotics to curb the infections contributes to relapse and is an important reason for the high mortality rate. Treatment failure may also be due to antibiotic tolerance. Accumulating evidence suggests that t the host immune environment plays an important role in inducing antibiotic tolerance of S. aureus, but research in this area has been limited.METHODS: In this study,the minimum inhibitory concentration (MIC) of the antibiotics against S. aureus was determined using the standard broth microdilution method.The study evaluated whether itaconate induces antibiotic tolerance in S. aureus through an antibiotic bactericidal activity assay.The effect of itaconate on the growth of S. aureus was evaluated by monitoring the growth of S. aureus in medium supplemented with itaconate. Additionally, RNA sequencing and metabolomics analyses were used to determine transcriptional and metabolic changes in S. aureus when exposed to itaconate.RESULTS AND DISCUSSION: According to the study,we found that the immune metabolite itaconate can induce tolerance in both methicillin-resistant and -susceptible S. aureus to aminoglycosides. When S. aureus was exposed to itaconate, its growth slowed down and transcriptomic and metabolomic alterations associated with decreased energy metabolism, including the tricarboxylate cycle, glycolysis, pyruvate metabolism, and arginine biosynthesis, were observed. These changes are associated with aminoglycoside tolerance. This study highlights the role of immune signaling metabolites in bacterial antibiotic tolerance and suggests new strategies to improve antibiotic treatment by modulating the host immune response and stimulating the metabolism of bacteria.PMID:39403084 | PMC:PMC11471559 | DOI:10.3389/fmicb.2024.1450085

Metabolomics of related C3 and C4 Flaveria species indicate differences in the operation of photorespiration under fluctuating light

Tue, 15/10/2024 - 12:00
Plant Direct. 2024 Oct 14;8(10):e70012. doi: 10.1002/pld3.70012. eCollection 2024 Oct.ABSTRACTC3 photosynthesis can be complemented with a C4 carbon concentrating mechanism (CCM) to minimize photorespiratory losses. C4 photosynthesis is often more efficient than C3 under steady-state conditions. However, the C4 CCM depends on inter-cellular metabolite concentration gradients, which must increase following increases in light intensity and could decrease rates of C4 photosynthesis under fluctuating light. Additionally, incomplete flux through photorespiration could prove beneficial to C4 assimilation during light induction of the CCM. Here, we compare metabolic profiles in the closely related C3 Flaveria robusta and C4 Flaveria bidentis during a light transient from low to high light to determine if these non-steady state accumulation patterns provide insight to the induction of the metabolite gradients needed to drive C4 intermediate transport and if there is incomplete cycling of photorespiratory intermediates. In these C3 and C4 species, metabolite steady-state pool sizes suggest that C4 transport acids maintain concentration gradients across the bundle sheath and mesophyll cell types under these light fluctuations. However, there was incomplete flux through photorespiration in the C4 F. bidentis, which could reduce photorespiratory CO2 loss via glycine decarboxylation and help maintain higher rates of assimilation during following induction periods.PMID:39403073 | PMC:PMC11473189 | DOI:10.1002/pld3.70012

Blood L-cystine levels positively related to increased risk of hypertension

Tue, 15/10/2024 - 12:00
J Clin Hypertens (Greenwich). 2024 Oct 15. doi: 10.1111/jch.14902. Online ahead of print.ABSTRACTHypertension is one component of metabolic syndrome (MetS). Here, the study evaluated hypertension-associated metabolites in relation to other MetS components. Fasting plasma samples were collected from 22 hypertensive and 63 normotensive subjects for non-targeted metabolomics. Compared with normotensive subjects, hypertensive patients were more diabetic (6.3% vs. 36.4%) and had dyslipidemia (27.0% vs. 63.6%) (both p < .05). By non-targeted metabolomics, 758 metabolites in 22 classes were identified and 56 were differentially regulated between hypertensive and normotensive groups. Amongst these 56 metabolites, receiver operating characteristic analysis showed that 14 had an area under the curve above 0.6. Multivariate-adjusted logistic regression analysis demonstrated that per one-fold increase of L-glutmatic acid, L-cystine, (9S,10E,12Z,15Z)-9-Hydroxy-10,12,15-octadecatrienoic acid, deoxyribose 5-phosphate, and falcarinolone, the odds ratios were 3.64, 4.61, 0.26, 0.26, and 0.37 for having the risk of hypertension, respectively. Of five metabolites, by Spearman's correlation analysis, only L-glutmatic acid and L-cystine levels were positively associated with systolic and diastolic blood pressure (all p < .05). Spearman's correlation analysis further revealed that L-glutmatic acid levels were positively correlated with to body mass index (BMI), fasting blood glucose, and serum triglyceride but negatively associated with HDL-c (all p < .05) whereas L-cystine levels were not related to any of these components (p ≥ .13). Multivariate-adjusted linear regression analysis confirmed the positive correlation between L-cystine levels and systolic or diastolic blood pressure (β = 2.66 for SBP; β = 2.50 for DBP; both p < .05). In conclusion, L-cystine could be a potent metabolite for increased risk of hypertension.PMID:39403054 | DOI:10.1111/jch.14902

Lifelong impacts of puberty timing on human plasma metabolic profiles: A metabolome-wide Mendelian randomization study

Tue, 15/10/2024 - 12:00
Diabetes Obes Metab. 2024 Oct 14. doi: 10.1111/dom.16000. Online ahead of print.ABSTRACTAIM: The aim was to investigate the causal relationship between puberty timing and plasma metabolites, accounting for birth weight, childhood and adulthood adiposity.MATERIALS AND METHODS: The meta-analysis of genome-wide association studies (GWAS) for puberty timing was extracted from the ReproGen Consortium, involving 329 345 women of European ancestry. Summary data for 174 plasma metabolites were retrieved from a recently conducted cross-platform GWAS that involved a meta-analysis of three cohort studies (i.e. the Fenland, European Prospective Investigation into Cancer-Norfolk and INTERVAL studies) and three publicly available studies and included up to 86 507 participants. We conducted a two-sample Mendelian randomization (MR) analysis to infer the causal relationship of puberty timing on 174 plasma metabolites, complemented by a two-step and multivariable Mendelian randomization (MVMR) analysis to assess direct and indirect effects. Additionally, summary-level data from the UK Biobank were used for our replication analysis.RESULTS: The results of the two-sample MR provide moderate evidence supporting a causal relationship between puberty timing and 23 of 174 plasma metabolites (i.e. 7 acylcarnitines, 8 amino acids, 2 biogenic amines and 6 lysophosphatidylcholines). Even after single-nucleotide polymorphisms associated with birth weight and childhood adiposity were excluded, causal effects persisted for 16 metabolites (i.e. 8 acylcarnitines, 4 amino acids, 2 biogenic amines and 2 lysophosphatidylcholines). The two-step MR analysis provided evidence that the relationship between puberty timing and plasma metabolites was mediated by adulthood adiposity. Additionally, moderate evidence emerged for an independent causal effect of puberty timing on 10 metabolites through an MVMR analysis (i.e. 5 acylcarnitines, 2 amino acids, 1 biogenic amine, 1 lysophosphatidylcholine and 1 phosphatidylcholine). Furthermore, the replication analysis suggested the robustness of our results.CONCLUSIONS: In summary, our study provides compelling evidence that puberty timing has a causal influence on certain plasma metabolites, although this influence is largely mediated by adulthood adiposity.PMID:39402736 | DOI:10.1111/dom.16000

Met4DX: A Unified and Versatile Data Processing Tool for Multidimensional Untargeted Metabolomics Data

Tue, 15/10/2024 - 12:00
J Am Soc Mass Spectrom. 2024 Oct 14. doi: 10.1021/jasms.4c00290. Online ahead of print.ABSTRACTLiquid chromatography-mass spectrometry (LC-MS) is a powerful tool in untargeted metabolomics, enabling the high-sensitivity and high-specificity characterization of metabolites. The integration of ion mobility (IM) with LC-MS, known as LC-IM-MS, enhances the analytical depth, facilitating more comprehensive metabolite profiling. However, the complexity of data generated by these technologies presents significant challenges in data processing. Addressing these challenges, we developed Met4DX, a unified and versatile software tool for processing both 3D and 4D untargeted metabolomics data. Met4DX incorporates a new MS1-oriented peak detection approach coupled with our bottom-up assembly algorithm, enabling highly sensitive and comprehensive peak detection in untargeted metabolomics data. Additionally, Met4DX employs a uniform quantification strategy to enhance the precision of peak integration across different samples. The software provides a user-friendly interface that simplifies data processing with default parameter sets, consolidating peak detection, alignment, quantification, and other procedures into a single streamlined workflow. Together, Met4DX offers a comprehensive solution for multidimensional metabolomics data processing, transforming raw data from diverse MS instruments into a final feature table containing quantification and identification results. We postulate Met4DX facilitates metabolite discovery in biological samples by deciphering the complex untargeted metabolomics data. Met4DX is freely available on the Internet (https://met4dx.zhulab.cn/).PMID:39402731 | DOI:10.1021/jasms.4c00290

Altered metabolic profiles in male offspring conceived from intracytoplasmic sperm injection

Mon, 14/10/2024 - 12:00
BMC Med. 2024 Oct 14;22(1):462. doi: 10.1186/s12916-024-03654-y.ABSTRACTBACKGROUND: While most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity.METHODS: We recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0-11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI).RESULTS: A total of 14,196 offspring visits were identified. In offspring aged 4-11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.03; total cholesterol z-score: adjusted mean difference: - 0.13, 95% CI: - 0.23 to - 0.02; LDL-C z-score: adjusted mean difference: - 0.12, 95% CI: - 0.22 to - 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: - 0.20, 95% CI: - 0.32 to - 0.08; total cholesterol z-score: adjusted mean difference: - 0.15, 95% CI: - 0.27 to - 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: - 0.21, 95% CI: - 0.37 to - 0.05).CONCLUSIONS: The findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children.PMID:39402563 | DOI:10.1186/s12916-024-03654-y

Genomic and functional characterization of the Atlantic salmon gut microbiome in relation to nutrition and health

Mon, 14/10/2024 - 12:00
Nat Microbiol. 2024 Oct 14. doi: 10.1038/s41564-024-01830-7. Online ahead of print.ABSTRACTTo ensure sustainable aquaculture, it is essential to understand the path 'from feed to fish', whereby the gut microbiome plays an important role in digestion and metabolism, ultimately influencing host health and growth. Previous work has reported the taxonomic composition of the Atlantic salmon (Salmo salar) gut microbiome; however, functional insights are lacking. Here we present the Salmon Microbial Genome Atlas consisting of 211 high-quality bacterial genomes, recovered by cultivation (n = 131) and gut metagenomics (n = 80) from wild and farmed fish both in freshwater and seawater. Bacterial genomes were taxonomically assigned to 14 different orders, including 35 distinctive genera and 29 previously undescribed species. Using metatranscriptomics, we functionally characterized key bacterial populations, across five phyla, in the salmon gut. This included the ability to degrade diet-derived fibres and release vitamins and other exometabolites with known beneficial effects, which was supported by genome-scale metabolic modelling and in vitro cultivation of selected bacterial species coupled with untargeted metabolomic studies. Together, the Salmon Microbial Genome Atlas provides a genomic and functional resource to enable future studies on salmon nutrition and health.PMID:39402236 | DOI:10.1038/s41564-024-01830-7

Multi-omics analysis of soil microbiota and metabolites in dryland wheat fields under different tillage methods

Mon, 14/10/2024 - 12:00
Sci Rep. 2024 Oct 14;14(1):24066. doi: 10.1038/s41598-024-74620-0.ABSTRACTNo-tillage and subsoiling can improve soil aggregate structure and realize a synergistic effect of soil carbon and nitrogen retention compared with deep tillage. This study aimed to investigate the effects of different tillage methods on the microbiome and metabolites in wheat rhizosphere. Results indicated that no significant differences in the diversity of soil bacterial and fungal communities were observed among the tillage methods. Analysis revealed that no-tillage enriched specific genera such as Cryptosporangium, Crossiella, Rhodothermaceae, Leptothrix, Stilbella, Diutina, and Pyrenochaetopsis, while subsoiling was associated with Rubrobacter, Latescibacteraceae, Nitrospira, Rokubacteriales, and Ctenomyces. Deep tillage, on the other hand, showed significant associations with Nocardia, Aeromicrobium, Sphingopyxis, Cordyceps, and Subulicystidium. Metabolomic analysis identified differential metabolites involved in various pathways, including the biosynthesis of plant secondary metabolites, ABC transporters, and starch and sucrose metabolism. Correlation analysis revealed a significant interaction between microorganisms and metabolites in wheat rhizosphere. Bacteria at the genus level exhibited greater associations with differential metabolites. In conclusion, different tillage practices can alter the composition of microbial communities and metabolites in wheat rhizosphere, and their interactions may affect soil fertility and wheat growth.PMID:39402065 | DOI:10.1038/s41598-024-74620-0

AKT/mTOR-mediated autophagic signaling is associated with TCDD-induced cleft palate

Mon, 14/10/2024 - 12:00
Reprod Toxicol. 2024 Oct 12:108731. doi: 10.1016/j.reprotox.2024.108731. Online ahead of print.ABSTRACTIn utero exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can contribute to high rates of cleft palate (CP) formation, but the mechanistic basis for these effects remains uncertain. Here, multi-omics-based metabolomic and transcriptomic analyses were employed to characterize the etiological basis for TCDD-induced CP on gestational day 14.5 (GD14.5). These analyses revealed that TCDD-induced CP formation is associated with calcium, MAPK, PI3K-Akt, and mTOR pathway signaling. PI3K-Akt and mTOR signaling activity is closely linked with the maintenance of cellular proliferation and survival. Moreover, mTOR-mediated regulation of autophagic activity is essential for ensuring an appropriate balance between metabolic activity and growth. Murine embryonic palatal mesenchymal (MEPM) cell proliferation was thus characterized, autophagic activity in these cells was evaluated through electron microscopy and western immunoblotting was used to compare the levels of autophagy- and AKT/mTOR-related protein between the control and TCDD groups on GD14.5. These analyses indicated that MEPM cell proliferative and autophagic activity was inhibited in response to TCDD exposure with the concomitant activation of AKT/mTOR signaling, in line with the multi-omics data. Together, these findings suggested that following TCDD exposure, the activation of AKT/mTOR-related autophagic signaling may play a role in the loss of appropriate palatal cell homeostasis, culminating in the incidence of CP.PMID:39401686 | DOI:10.1016/j.reprotox.2024.108731

Toxicity of parental co-exposure of microplastic and bisphenol compounds on adult zebrafish: Multi-omics investigations on offspring

Mon, 14/10/2024 - 12:00
Sci Total Environ. 2024 Oct 12:176897. doi: 10.1016/j.scitotenv.2024.176897. Online ahead of print.ABSTRACTIn recent years, the widespread use of bisphenol compounds and microplastics (MP) have attracted attention due to their harmful effects. Here, individual and combined effects of MP and bisphenol compounds, were assessed on adult zebrafish after co-exposure of bisphenol A (BPA) or bisphenol S (BPS) and 25 μm polyethylene MP. Impacts on their offspring (the F1 generation) were also investigated. The reproductive toxicity in adult zebrafish impacted exerted by bisphenol compounds were aggravated by the co-presence of MP. Transcriptomics and metabolomics further showed single or co-exposure of bisphenol compounds and MP could together regulate apoptosis, calcium signaling pathway and glycerophospholipid signaling pathways. Our results also showed the different toxicity mechanisms on transcriptional and metabolic profiles in the combination effects of bisphenol compounds and MP. The co-exposure of BPA and MP predominantly influenced neurotoxicity via the MAPK signaling pathway and voltage-dependent calcium channels, whereas the co-exposure of BPS and MP principally affected visual development through phototransduction and retinol metabolism. The co-exposure of BPA and MP, as well as BPS and MP, specifically regulate lipid metabolism and carbohydrate metabolism in zebrafish offspring, respectively. Overall, this study provided a deep understanding of the toxicity differences between co-exposure and single exposure of bisphenol compound and MP in zebrafish, as well as the transgenerational effects and potential molecular mechanisms of bisphenol compounds and MP in zebrafish offspring.PMID:39401590 | DOI:10.1016/j.scitotenv.2024.176897

Multi-omics analysis reveal the fall armyworm Spodoptera frugiperda tolerate high temperature by mediating chitin-related genes

Mon, 14/10/2024 - 12:00
Insect Biochem Mol Biol. 2024 Oct 12:104192. doi: 10.1016/j.ibmb.2024.104192. Online ahead of print.ABSTRACTClimate change facilitates the rapid invasion of agricultural pests, threatening global food security. The fall armyworm Spodoptera frugiperda is a highly polyphagous migratory pest tolerant to high temperatures, allowing its proliferation in harsh thermal environments. We aimed to demonstrated mechanisms of its high-temperature tolerance, particularly transcriptional and metabolic regulation, which are poorly understood. To achieve the aim, we examined the impact and mechanism of heat events on S. frugiperda by using multiple approaches: ecological measurements, transcriptomics, metabolomics, RNAi, and CRISPR/Cas9 technology. We observed that several physiological indices (larval survival rate, larval period, pupation rate, pupal weight, eclosion rate, and average fecundity) decreased as the temperature increased, with the 32°C treatment displaying a significant difference from the control group at 26°C. Significantly upregulated expression of genes encoding endochitinase and chitin deacetylase was observed in the chitin-binding, extracellular region, and carbohydrate metabolic process GO terms of hemolymph, fat body, and brain, exhibiting a tissue-specific pattern. Significantly enriched pathways (e.g., cutin, suberin, and wax biosynthesis; oxidative phosphorylation and cofactor biosynthesis; diverse amino acid biosynthesis and degradation; carbon metabolism; and energy metabolism), all of which are essential for S. frugiperda larvae to tolerate temperature, were found in metabolites that were expressed differently. Successful RNA interference targeting of the three chitin-related genes reduced gene expression levels and larval survival rate. Knockout of the endochitinase gene by using the CRISPR/Cas9 system significantly reduced the relative gene expression and increased sensitivity to high-temperature exposure. On the basis of our findings, theoretical foundations for understanding the high-temperature tolerance of S. frugiperda populations and latent genetic control strategies were established.PMID:39401552 | DOI:10.1016/j.ibmb.2024.104192

Correction to Teruya et al., Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites

Mon, 14/10/2024 - 12:00
Proc Natl Acad Sci U S A. 2024 Oct 22;121(43):e2419538121. doi: 10.1073/pnas.2419538121. Epub 2024 Oct 14.NO ABSTRACTPMID:39401367 | DOI:10.1073/pnas.2419538121

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