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

Analysis of Inhibitory Behaviour of Ferulic Acid and p-Coumaric Acid on Saccharomyces Cerevisiae Cells

Sun, 26/11/2023 - 12:00
Stud Health Technol Inform. 2023 Nov 23;308:365-371. doi: 10.3233/SHTI230861.ABSTRACTMetabolomics has been widely used to identify changes in relevant differential metabolites. The metabolites of Saccharomyces cerevisiae cells supplemented with ferulic acid and p-coumaric acid were prepared and extracted. Untargeted metabolomics analysis of saccharomyces cerevisiae metabolites was performed. In addition, GNPS, Respect and MassBank databases were used to search and compare the information in the whole database. It was found that 100 and 92 different metabolites were significantly changed (P value < 0.05,VIP value > 1,) in Saccharomyces cerevisiae cells treated with ferulic acid and p-coumaric acid respectively. Including isothiocyanate, L-threonine, adenosine, glycerin phospholipid choline, niacinamide and palmitic acid. These metabolites with significant differences were enriched by KEGG pathway using MetPA database.PMID:38007761 | DOI:10.3233/SHTI230861

Multi-omics analysis of hospital-acquired diarrhoeal patients reveals biomarkers of enterococcal proliferation and Clostridioides difficile infection

Sat, 25/11/2023 - 12:00
Nat Commun. 2023 Nov 25;14(1):7737. doi: 10.1038/s41467-023-43671-8.ABSTRACTHospital-acquired diarrhoea (HAD) is common, and often associated with gut microbiota and metabolome dysbiosis following antibiotic administration. Clostridioides difficile is the most significant antibiotic-associated diarrhoeal (AAD) pathogen, but less is known about the microbiota and metabolome associated with AAD and C. difficile infection (CDI) with contrasting antibiotic treatment. We characterised faecal microbiota and metabolome for 169 HAD patients (33 with CDI and 133 non-CDI) to determine dysbiosis biomarkers and gain insights into metabolic strategies C. difficile might use for gut colonisation. The specimen microbial community was analysed using 16 S rRNA gene amplicon sequencing, coupled with untargeted metabolite profiling using gas chromatography-mass spectrometry (GC-MS), and short-chain fatty acid (SCFA) profiling using GC-MS. AAD and CDI patients were associated with a spectrum of dysbiosis reflecting non-antibiotic, short-term, and extended-antibiotic treatment. Notably, extended antibiotic treatment was associated with enterococcal proliferation (mostly vancomycin-resistant Enterococcus faecium) coupled with putative biomarkers of enterococcal tyrosine decarboxylation. We also uncovered unrecognised metabolome dynamics associated with concomitant enterococcal proliferation and CDI, including biomarkers of Stickland fermentation and amino acid competition that could distinguish CDI from non-CDI patients. Here we show, candidate metabolic biomarkers for diagnostic development with possible implications for CDI and vancomycin-resistant enterococci (VRE) treatment.PMID:38007555 | DOI:10.1038/s41467-023-43671-8

Plasma metabolomics profiling of 580 patients from an Early Detection Research Network prostate cancer cohort

Sat, 25/11/2023 - 12:00
Sci Data. 2023 Nov 25;10(1):830. doi: 10.1038/s41597-023-02750-7.ABSTRACTProstate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.PMID:38007532 | DOI:10.1038/s41597-023-02750-7

Plasma metabolite predictors of metabolic syndrome incidence and reversion

Sat, 25/11/2023 - 12:00
Metabolism. 2023 Nov 23:155742. doi: 10.1016/j.metabol.2023.155742. Online ahead of print.ABSTRACTBACKGROUND: Metabolic Syndrome (MetS) is a progressive pathophysiological state defined by a cluster of cardiometabolic traits. However, little is known about metabolites that may be predictors of MetS incidence or reversion. Our objective was to identify plasma metabolites associated with MetS incidence or MetS reversion.METHODS: The study included 1468 participants without cardiovascular disease (CVD) but at high CVD risk at enrollment from two case-cohort studies nested within the PREvención con DIeta MEDiterránea (PREDIMED) study with baseline metabolomics data. MetS was defined in accordance with the harmonized International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute criteria, which include meeting 3 or more thresholds for waist circumference, triglyceride, HDL cholesterol, blood pressure, and fasting blood glucose. MetS incidence was defined by not having MetS at baseline but meeting the MetS criteria at a follow-up visit. MetS reversion was defined by MetS at baseline but not meeting MetS criteria at a follow-up visit. Plasma metabolome was profiled by LC-MS. Multivariable-adjusted Cox regression models and elastic net regularized regressions were used to assess the association of 385 annotated metabolites with MetS incidence and MetS reversion after adjusting for potential risk factors.RESULTS: Of the 603 participants without baseline MetS, 298 developed MetS over the median 4.8-year follow-up. Of the 865 participants with baseline MetS, 285 experienced MetS reversion. A total of 103 and 88 individual metabolites were associated with MetS incidence and MetS reversion, respectively, after adjusting for confounders and false discovery rate correction. A metabolomic signature comprised of 77 metabolites was robustly associated with MetS incidence (HR: 1.56 (95 % CI: 1.33-1.83)), and a metabolomic signature of 83 metabolites associated with MetS reversion (HR: 1.44 (95 % CI: 1.25-1.67)), both p < 0.001. The MetS incidence and reversion signatures included several lipids (mainly glycerolipids and glycerophospholipids) and branched-chain amino acids.CONCLUSION: We identified unique metabolomic signatures, primarily comprised of lipids (including glycolipids and glycerophospholipids) and branched-chain amino acids robustly associated with MetS incidence; and several amino acids and glycerophospholipids associated with MetS reversion. These signatures provide novel insights on potential distinct mechanisms underlying the conditions leading to the incidence or reversion of MetS.TWEET: A new study from @HarvardChanSPH led by @zsemnani and @MartaGuasch1 shows unique #metabolomic signatures associated with metabolic syndrome incidence and reversion using data from the PREDIMED study.PMID:38007148 | DOI:10.1016/j.metabol.2023.155742

Enhanced reproductive toxicity of photodegraded polylactic acid microplastics in zebrafish

Sat, 25/11/2023 - 12:00
Sci Total Environ. 2023 Nov 23:168742. doi: 10.1016/j.scitotenv.2023.168742. Online ahead of print.ABSTRACTMicroplastics are widely used due to their numerous advantages. However, they can have detrimental effects on marine ecosystems. When microplastics enter the ocean, they can be absorbed by marine organisms, leading to toxic effects. Additionally, the transformation of microplastics during natural degradation can alter their toxicity, necessitating further investigation. Polylactic acid (PLA) biodegradable plastics are commonly used, yet research on their toxicity, particularly their reproductive effects on aquatic organisms, remains limited. In this study, we conducted photodegradation of PLA using potassium persulfate as a catalyst to simulate natural degradation conditions. Our objective was to assess the reproductive toxicity of photodegraded PLA microplastics on zebrafish. The results revealed that photodegraded PLA exhibited elevated reproductive toxicity, resulting in abnormal oocyte differentiation, disruption of sexual hormone levels, and alterations in ovarian tissue metabolism. Metabolomics analysis indicated that both unphotodegraded PLA (UPLA) and photodegraded PLA (DPLA) disrupted oxidative stress homeostasis in zebrafish ovarian tissue by influencing pathways such as purine metabolism, phenylalanine metabolism, glutathione metabolism, and riboflavin metabolism. Furthermore, the DPLA treatment induced abnormal biosynthesis of taurocholic acid, which was not observed in the UPLA treatment group. Importantly, the DPLA treatment group exhibited more pronounced effects on offspring development compared to the UPLA treatment group, characterized by higher mortality rates, inhibition of embryo hatching, accelerated heart rates, and reduced larval body length. These findings underscore the varying levels of toxicity to zebrafish ovaries before and after PLA photodegradation, along with evidence of intergenerational toxicity.PMID:38007130 | DOI:10.1016/j.scitotenv.2023.168742

A review of the epidemiological and laboratory evidence of the role of aluminum exposure in pathogenesis of cardiovascular diseases

Sat, 25/11/2023 - 12:00
Environ Res. 2023 Nov 23:117740. doi: 10.1016/j.envres.2023.117740. Online ahead of print.ABSTRACTThe objective of the present study was to review the epidemiological and laboratory evidence on the role of aluminum (Al) exposure in the pathogenesis of cardiovascular diseases. Epidemiological data demonstrated an increased incidence of cardiovascular diseases (CVD), including hypertension and atherosclerosis in occupationally exposed subjects and hemodialysis patients. In addition, Al body burden was found to be elevated in patients with coronary heart disease, hypertension, and dyslipidemia. Laboratory studies demonstrated that Al exposure induced significant ultrastructural damage in the heart, resulting in electrocardiogram alterations in association with cardiomyocyte necrosis and apoptosis, inflammation, oxidative stress, inflammation, and mitochondrial dysfunction. In agreement with the epidemiological findings, laboratory data demonstrated dyslipidemia upon Al exposure, resulting from impaired hepatic lipid catabolism, as well as promotion of low-density lipoprotein oxidation. Al was also shown to inhibit paraoxonase 1 activity and to induce endothelial dysfunction and adhesion molecule expression, further promoting atherogenesis. The role of Al in hypertension was shown to be mediated by up-regulation of NADPH-oxidase, inhibition of nitric oxide bioavailability, and stimulation of renin-angiotensin-aldosterone system. It has been also demonstrated that Al exposure targets cerebral vasculature, which may be considered a link between Al exposure and cerebrovascular diseases. Findings from other tissues lend support that ferroptosis, pyroptosis, endoplasmic reticulum stress, and modulation of gut microbiome and metabolome are involved in the development of CVD upon Al exposure. A better understanding of the role of the cardiovascular system as a target for Al toxicity will be useful for risk assessment and the development of treatment and prevention strategies.PMID:38007081 | DOI:10.1016/j.envres.2023.117740

Sophora tonkinensis and active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency in myocardial ischemia mice through regulating the vesicle-mediated transport pathway

Sat, 25/11/2023 - 12:00
Fitoterapia. 2023 Nov 23:105756. doi: 10.1016/j.fitote.2023.105756. Online ahead of print.ABSTRACTAncient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1β, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.PMID:38007052 | DOI:10.1016/j.fitote.2023.105756

Evaluation of novel candidate filtration markers from a global metabolomic discovery for glomerular filtration rate estimation

Sat, 25/11/2023 - 12:00
Kidney Int. 2023 Nov 23:S0085-2538(23)00784-6. doi: 10.1016/j.kint.2023.11.007. Online ahead of print.ABSTRACTCreatinine and cystatin-C are recommended for estimating glomerular filtration rate (eGFR) but accuracy is suboptimal. Here, using untargeted metabolomics data, we sought to identify candidate filtration markers for a new targeted assay using a novel approach based on their maximal joint association with measured GFR (mGFR) and with flexibility to consider their biological properties. We analyzed metabolites measured in seven diverse studies encompasing 2,851 participants on the Metabolon H4 platform that had Pearson correlations with log mGFR and used a stepwise approach to develop models to < -0.5 estimate mGFR with and without inclusion of creatinine that enabled selection of candidate markers. In total, 456 identified metabolites were present in all studies, and 36 had correlations with mGFR < -0.5. A total of 2,225 models were developed that included these metabolites; all with lower root mean square errors and smaller coefficients for demographic variables compared to estimates using untargeted creatinine. Seventeen metabolites were chosen, including 12 new candidate filtration markers. The selected metabolites had strong associations with mGFR and little dependence on demographic factors. Candidate metabolites were identified with maximal joint association with mGFR and minimal dependence on demographic variables across many varied clinical settings. These metabolites are excreted in urine and represent diverse metabolic pathways and tubular handling. Thus, our data can be used to select metabolites for a multi-analyte eGFR determination assay using mass spectrometry that potentially offers better accuracy and is less prone to non-GFR determinants than the current eGFR biomarkers.PMID:38006943 | DOI:10.1016/j.kint.2023.11.007

Species discrimination of multiple botanical origins of Fritillaria species based on infrared spectroscopy, thin layer chromatography-image analysis and untargeted metabolomics

Sat, 25/11/2023 - 12:00
Phytomedicine. 2023 Nov 19;123:155228. doi: 10.1016/j.phymed.2023.155228. Online ahead of print.ABSTRACTBACKGROUND: Fritillaria Bulbus (FB), a precious medicinal herb renowned for its heat-clearing, lung-moistening, cough-relieving and phlegm-eliminating effects. In pursuit of profits, unscrupulous merchants have engaged in the substitution or adulteration of valuable varieties with cheaper alternatives. It is, therefore, urgent to develop effective technical approaches to identify FBs from adulterants.METHODS: This paper employed infrared spectroscopy (IR), thin layer chromatography-image analysis (TLC-IA), and untargeted metabolomics techniques to discriminate ten species of FBs.RESULTS: Five species of FBs were successfully differentiated using mid-infrared spectroscopy. Furthermore, the power of TLC-IA technology allowed the differentiation of five species of FBs and two origins of FCBs (Fritillariae Cirrhosae Bulbus). Remarkably, through the application of untargeted metabolomics technique, the precise discrimination of five species of FBs, as well as three origins of FCBs were accomplished. Moreover, a comprehensive identification of 101 markers that reliably distinguished diverse FBs was achieved through the employment of untargeted metabolomics technique.CONCLUSION: The investigation presented powerful means of detection for assuring the quality control of Fritillaria herbs.PMID:38006808 | DOI:10.1016/j.phymed.2023.155228

Longitudinal lipidomic profiles during pregnancy and associations with neonatal anthropometry: findings from a multiracial cohort

Sat, 25/11/2023 - 12:00
EBioMedicine. 2023 Nov 24;98:104881. doi: 10.1016/j.ebiom.2023.104881. Online ahead of print.ABSTRACTBACKGROUND: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort.METHODS: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using weighted correlation network analysis and common networks using consensus network analysis across four visits using linear mixed-effects models with the adjustment of false discover rate.FINDINGS: Multiple triglycerides (TG) were positively associated with birth weight (BW), BW Z-score, length and head circumference, while some cholesteryl ester (CE), phosphatidylcholine (PC), sphingomyelines (SM), phosphatidylethanolamines (PE), and lysophosphatidylcholines (LPC 20:3) families were inversely associated with BW, length, abdominal and head circumference at different GWs. Longitudinal trajectories of TG, PC, and glucosylcermides (GlcCer) were associated with BW, and CE (18:2) with BW z-score, length, and sum of skinfolds (SS), while some PC and PE were significantly associated with abdominal and head circumference. Modules of TG at GW 10-14 and 15-26 mainly were associated with BW. At GW 33-39, two networks of LPC (20:3) and of PC, TG, and CE, showed inverse associations with abdominal circumference. Distinct trajectories within two consensus modules with changes in TG, CE, PC, and LPC showed significant differences in BW and length.INTERPRETATION: The results demonstrated that longitudinal changes of TGs during early- and mid-pregnancy and changes of PC, LPC, and CE during late-pregnancy were significantly associated with neonatal anthropometry.FUNDING: National Institute of Child Health and Human Development intramural funding.PMID:38006745 | DOI:10.1016/j.ebiom.2023.104881

Anaerobic pathogens associated with OSA may contribute to pathophysiology via amino-acid depletion

Sat, 25/11/2023 - 12:00
EBioMedicine. 2023 Nov 24;98:104891. doi: 10.1016/j.ebiom.2023.104891. Online ahead of print.ABSTRACTBACKGROUND: The human microbiome is linked to multiple metabolic disorders such as obesity and diabetes. Obstructive sleep apnoea (OSA) is a common sleep disorder with several metabolic risk factors. We investigated the associations between the gut microbiome composition and function, and measures of OSA severity in participants from a prospective community-based cohort study: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).METHODS: Bacterial-Wide Association Analysis (BWAS) of gut microbiome measured via metagenomics with OSA measures was performed adjusting for clinical, lifestyle and co-morbidities. This was followed by functional analysis of the OSA-enriched bacteria. We utilized additional metabolomic and transcriptomic associations to suggest possible mechanisms explaining the microbiome effects on OSA.FINDINGS: Several uncommon anaerobic human pathogens were associated with OSA severity. These belong to the Lachnospira, Actinomyces, Kingella and Eubacterium genera. Functional analysis revealed enrichment in 49 processes including many anaerobic-related ones. Severe OSA was associated with the depletion of the amino acids glycine and glutamine in the blood, yet neither diet nor gene expression revealed any changes in the production or consumption of these amino acids.INTERPRETATION: We show anaerobic bacterial communities to be a novel component of OSA pathophysiology. These are established in the oxygen-poor environments characteristic of OSA. We hypothesize that these bacteria deplete certain amino acids required for normal human homeostasis and muscle tone, contributing to OSA phenotypes. Future work should test this hypothesis as well as consider diagnostics via anaerobic bacteria detection and possible interventions via antibiotics and amino-acid supplementation.FUNDING: Described in methods.PMID:38006744 | DOI:10.1016/j.ebiom.2023.104891

Metabolome subtyping reveals multi-omics characteristics and biological heterogeneity in major psychiatric disorders

Sat, 25/11/2023 - 12:00
Psychiatry Res. 2023 Nov 13;330:115605. doi: 10.1016/j.psychres.2023.115605. Online ahead of print.ABSTRACTGrowing evidence suggests that major psychiatric disorders (MPDs) share common etiologies and pathological processes. However, the diagnosis is currently based on descriptive symptoms, which ignores the underlying pathogenesis and hinders the development of clinical treatments. This highlights the urgency of characterizing molecular biomarkers and establishing objective diagnoses of MPDs. Here, we collected untargeted metabolomics, proteomics and DNA methylation data of 327 patients with MPDs, 131 individuals with genetic high risk and 146 healthy controls to explore the multi-omics characteristics of MPDs. First, differential metabolites (DMs) were identified and we classified MPD patients into 3 subtypes based on DMs. The subtypes showed distinct metabolomics, proteomics and DNA methylation signatures. Specifically, one subtype showed dysregulation of complement and coagulation proteins, while the DNA methylation showed abnormalities in chemical synapses and autophagy. Integrative analysis in metabolic pathways identified the important roles of the citrate cycle, sphingolipid metabolism and amino acid metabolism. Finally, we constructed prediction models based on the metabolites and proteomics that successfully captured the risks of MPD patients. Our study established molecular subtypes of MPDs and elucidated their biological heterogeneity through a multi-omics investigation. These results facilitate the understanding of pathological mechanisms and promote the diagnosis and prevention of MPDs.PMID:38006718 | DOI:10.1016/j.psychres.2023.115605

Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study

Sat, 25/11/2023 - 12:00
Atherosclerosis. 2023 Nov 10;386:117382. doi: 10.1016/j.atherosclerosis.2023.117382. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: The lipid profile is consistently associated with coronary artery disease (CAD) and ischemic stroke (IS). However, the lipoprotein subfractions have not been deeply explored in stroke subtypes, especially in IS outcome.METHODS: We performed two-sample Mendelian randomization (MR) analysis using 92 lipid traits measured by nuclear magnetic resonance in 115,000 subjects from the UK Biobank. Data for genetic associations with IS, its subtypes, and long-term outcome (LTO) were obtained from three cohorts of European ancestry: GIGASTROKE (73,652 cases, 1,234,808 controls), GODS (n = 1791) and GISCOME (n = 6165). Results obtained using CARDIoGRAMPlusC4D were used to identify differences with CAD.RESULTS: Genetically determined low concentration of medium high-density lipoprotein (HDL) particles (odds ratio (OR) = 0.92, 95% CI 0.88-0.96; p = 3.6 × 10-4) and its cholesterol content (OR = 0.92, 95% CI 0.88-0.96; p = 1.9 × 10-4) showed causal associations with an increased risk of stroke. Genetic predisposition to high apolipoprotein (apo)B to apoA-I ratio was causally associated with an increased risk of IS (OR = 1.12, 95% CI 1.06-1.18, p = 1.1 × 10-4), and a highly suggestive association was found between non-esterified cholesterol in low-density lipoprotein (LDL) and increased risk of atherothrombotic stroke (LAS) (OR = 1.35, 95% CI 1.10-1.66; p = 4.0 × 10-3). Low cholesterol in small and medium LDL was suggestively associated with poor LTO.CONCLUSIONS: Our results support that low medium HDL concentration was causally associated with an increased stroke risk, while high levels of non-esterified cholesterol in LDL were suggestively associated with an increased risk of LAS and with a better LTO.PMID:38006695 | DOI:10.1016/j.atherosclerosis.2023.117382

Growth performance, bile acid profile, fecal microbiome and serum metabolomics of growing-finishing pigs fed diets with bile acids supplementation

Sat, 25/11/2023 - 12:00
J Anim Sci. 2023 Nov 25:skad393. doi: 10.1093/jas/skad393. Online ahead of print.ABSTRACTThe present experiment was conducted to determine the effect of bile acids (BAs) supplementation on growth performance, BAs profile, fecal microbiome, and serum metabolomics in growing-finishing pigs. A total of 60 pigs [Duroc × (Landrace ×Yorkshire)] with an average body weight of 27.0 ± 1.5 kg were selected and allotted into one of 2 groups (castrated male to female ratio = 1:1), with 10 replicates per treatment and 3 pigs per replicate. The 2 treatments were the control group (Control) and a porcine bile extract supplemented group dosed at 0.5 g/kg feed (BA). After a 16-wk treatment, growth performance, BAs profiles in serum and feces and fecal microbial composition were determined. An untargeted metabolomics approach using gas chromatography with a time-of-flight mass spectrometer (GC-TOF-MS) was conducted to identify the metabolic pathways and associated metabolites in the serum of pigs. We found that BAs supplementation had no effect on the growth performance of the growing-finishing pig. However, it tended to increase the gain to feed ratio for the whole period (P = 0.07). Bile acids supplementation resulted in elevated serum concentrations of secondary BAs (SBA), including hyodeoxycholic acid (HDCA), glycoursodeoxycholic acid (GUDCA), and tauro-hyodeoxycholic acid (THDCA), as well as fecal concentration of HDCA (P < 0.05). Fecal microbiota analysis revealed no differences in alpha and beta diversity indices or the relative abundance of Operational Taxonomic Units (OTUs) at both phylum and genus levels between groups. Metabolic pathway analysis revealed that the differential metabolites between Control and BA groups mainly involved in purine metabolism, ether lipid metabolism, glycerophospholipid metabolism, and amino sugar and nucleotide sugar metabolism, as well as primary bile acid biosynthesis. Our findings indicate that BAs supplementation tended to improve the feed efficiency, and significantly altered the BA profile in the serum and feces of growing-finished pigs, regardless of any changes in the gut microbial composition. The altered metabolic pathways could potentially play a vital role in improving the feed efficiency of growing-finished pigs with BAs supplementation.PMID:38006392 | DOI:10.1093/jas/skad393

Seminal plasma metabolomics analysis of differences in liquid preservation ability of boar sperm

Sat, 25/11/2023 - 12:00
J Anim Sci. 2023 Nov 25:skad392. doi: 10.1093/jas/skad392. Online ahead of print.ABSTRACTThe preservation of semen is pivotal in animal reproduction to ensure successful fertilization and genetic improvement of livestock and poultry. However, investigating the underlying causes of differences in sperm liquid preservation ability and identifying relevant biomarkers remains a challenge. This study utilized liquid chromatography-mass spectrometry (LC-MS) to analyze the metabolite composition of seminal plasma (SP) from two groups with extreme differences in sperm liquid preservation ability. The two groups namely the good liquid preservation ability (GPA) and the poor preservation ability (PPA). The aim was to explore the relationship between metabolite composition in SP and sperm liquid preservation ability, and to identify candidate biomarkers associated with this ability of sperm. The results revealed the identification of 756 metabolites and 70 differentially expressed metabolites (DEM) in the SP from two groups of boar semen with differing liquid preservation abilities at 17 ℃. The majority of identified metabolites in the SP belonged to organic acids and derivatives as well as lipids and lipid-like molecules. The DEM in the SP primarily consisted of amino acids, peptides, and analogues. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis also demonstrated that the DEM are mainly concentrated in amino acid synthesis and metabolism related pathways (P < 0.05). Furthermore, eleven key metabolites were identified and six target amino acids were verified, and the results were consistent with the non-targeted metabolic analysis. These findings indicated that amino acids and their associated pathways play a potential role in determining boar sperm quality and liquid preservation ability. D-proline, arginine, L-citrulline, phenylalanine, leucine, DL-proline, DL-serine, and indole may serve as potential biomarkers for early assessment of boar sperm liquid preservation ability. The findings of this study are helpful to understand the causes and mechanisms of differences in liquid preservation ability of boar sperm, and provide valuable insights for improving semen quality assessment methods and developing novel extenders or protocols.PMID:38006391 | DOI:10.1093/jas/skad392

Potential anti-inflammatory biomarkers from Myrtaceae essential oils revealed by untargeted metabolomics

Sat, 25/11/2023 - 12:00
Nat Prod Res. 2023 Nov 24:1-8. doi: 10.1080/14786419.2023.2283758. Online ahead of print.ABSTRACTMany species from Myrtaceae have traditionally been used in traditional medicine as anti-inflammatory, antimicrobial, antidiarrheal, antioxidant and antirheumatic, besides in blood cholesterol reduction. In the present work, the anti-inflammatory activity of essential oils from eighteen Myrtaceae spp. were evaluated according to their ex-vivo anti-inflammatory activity in human blood, and the corresponding biomarkers were determined using untargeted metabolomics data and multivariate data analysis. From these studied species, six displayed anti-inflammatory activity with percentage rates of inhibition of PGE2 release above 70%. Caryophyllene oxide (1), humulene epoxide II (2), β-selinene (3), α-amorphene (4), α-selinene (5), germacrene A (6), β-bisabolene (7), α-muurolene (8), α-humulene (9), β-gurjunene (10), myrcene (11), β-elemene (12), α-cadinol (13), α-copaene (14), E-nerolidol (15) and ledol (16) were annotated as potential anti-inflammatory biomarkers. The results obtained in this study point to essential oils from species of the Myrtaceae family as a rich source of anti-inflammatory agents.PMID:38006221 | DOI:10.1080/14786419.2023.2283758

Molecular Mechanisms Regulating Phenylpropanoid Metabolism in Exogenously-Sprayed Ethylene Forage Ramie Based on Transcriptomic and Metabolomic Analyses

Sat, 25/11/2023 - 12:00
Plants (Basel). 2023 Nov 18;12(22):3899. doi: 10.3390/plants12223899.ABSTRACTRamie (Boehmeria nivea [L.] Gaud.), a nutritious animal feed, is rich in protein and produces a variety of secondary metabolites that increase its palatability and functional composition. Ethylene (ETH) is an important plant hormone that regulates the growth and development of various crops. In this study, we investigated the impact of ETH sprays on the growth and metabolism of forage ramie. We explored the mechanism of ETH regulation on the growth and secondary metabolites of forage ramie using transcriptomic and metabolomic analyses. Spraying ramie with ETH elevated the contents of flavonoids and chlorogenic acid and decreased the lignin content in the leaves and stems. A total of 1076 differentially expressed genes (DEGs) and 51 differentially expressed metabolites (DEMs) were identified in the leaves, and 344 DEGs and 55 DEMs were identified in the stems. The DEGs that affect phenylpropanoid metabolism, including BGLU41, LCT, PER63, PER42, PER12, PER10, POD, BAHD1, SHT, and At4g26220 were significantly upregulated in the leaves. Ethylene sprays downregulated tyrosine and chlorogenic acid (3-O-caffeoylquinic acid) in the leaves, but lignin biosynthesis HCT genes, including ACT, BAHD1, and SHT, were up- and downregulated. These changes in expression may ultimately reduce lignin biosynthesis. In addition, the upregulation of caffeoyl CoA-O-methyltransferase (CCoAOMT) may have increased the abundance of its flavonoids. Ethylene significantly downregulated metabolites, affecting phenylpropanoid metabolism in the stems. The differential 4CL and HCT metabolites were downregulated, namely, phenylalanine and tyrosine. Additionally, ETH upregulated 2-hydroxycinnamic acid and the cinnamyl hydroxyl derivatives (caffeic acid and p-coumaric acid). Cinnamic acid is a crucial intermediate in the shikimic acid pathway, which serves as a precursor for the biosynthesis of flavonoids and lignin. The ETH-decreased gene expression and metabolite alteration reduced the lignin levels in the stem. Moreover, the HCT downregulation may explain the inhibited lignin biosynthesis to promote flavonoid biosynthesis. In conclusion, external ETH application can effectively reduce lignin contents and increase the secondary metabolites of ramie without affecting its growth and development. These results provide candidate genes for improving ramie and offer theoretical and practical guidance for cultivating ramie for forage.PMID:38005796 | DOI:10.3390/plants12223899

Exploring Human Metabolome after Wine Intake-A Review

Sat, 25/11/2023 - 12:00
Molecules. 2023 Nov 15;28(22):7616. doi: 10.3390/molecules28227616.ABSTRACTWine has a rich history dating back to 2200 BC, originally recognized for its medicinal properties. Today, with the aid of advanced technologies like metabolomics and sophisticated analytical techniques, we have gained remarkable insights into the molecular-level changes induced by wine consumption in the human organism. This review embarks on a comprehensive exploration of the alterations in human metabolome associated with wine consumption. A great number of 51 studies from the last 25 years were reviewed; these studies systematically investigated shifts in metabolic profiles within blood, urine, and feces samples, encompassing both short-term and long-term studies of the consumption of wine and wine derivatives. Significant metabolic alterations were observed in a wide variety of metabolites belonging to different compound classes, such as phenolic compounds, lipids, organic acids, and amino acids, among others. Within these classes, both endogenous metabolites as well as diet-related metabolites that exhibited up-regulation or down-regulation following wine consumption were included. The up-regulation of short-chain fatty acids and the down-regulation of sphingomyelins after wine intake, as well as the up-regulation of gut microbial fermentation metabolites like vanillic and syringic acid are some of the most important findings reported in the reviewed literature. Our results confirm the intact passage of certain wine compounds, such as tartaric acid and other wine acids, to the human organism. In an era where the health effects of wine consumption are of growing interest, this review offers a holistic perspective on the metabolic underpinnings of this centuries-old tradition.PMID:38005338 | DOI:10.3390/molecules28227616

Detrimental Impacts of Pharmaceutical Excipient PEG400 on Gut Microbiota and Metabolome in Healthy Mice

Sat, 25/11/2023 - 12:00
Molecules. 2023 Nov 13;28(22):7562. doi: 10.3390/molecules28227562.ABSTRACTPolyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.PMID:38005284 | DOI:10.3390/molecules28227562

Non-Targeted Spectranomics for the Early Detection of <em>Xylella fastidiosa</em> Infection in Asymptomatic Olive Trees, cv. Cellina di Nardò

Sat, 25/11/2023 - 12:00
Molecules. 2023 Nov 9;28(22):7512. doi: 10.3390/molecules28227512.ABSTRACTOlive quick decline syndrome (OQDS) is a disease that has been seriously affecting olive trees in southern Italy since around 2009. During the disease, caused by Xylella fastidiosa subsp. pauca sequence type ST53 (Xf), the flow of water and nutrients within the trees is significantly compromised. Initially, infected trees may not show any symptoms, making early detection challenging. In this study, young artificially infected plants of the susceptible cultivar Cellina di Nardò were grown in a controlled environment and co-inoculated with additional xylem-inhabiting fungi. Asymptomatic leaves of olive plants at an early stage of infection were collected and analyzed using nuclear magnetic resonance (NMR), hyperspectral reflectance (HSR), and chemometrics. The application of a spectranomic approach contributed to shedding light on the relationship between the presence of specific hydrosoluble metabolites and the optical properties of both asymptomatic Xf-infected and non-infected olive leaves. Significant correlations between wavebands located in the range of 530-560 nm and 1380-1470 nm, and the following metabolites were found to be indicative of Xf infection: malic acid, fructose, sucrose, oleuropein derivatives, and formic acid. This information is the key to the development of HSR-based sensors capable of early detection of Xf infections in olive trees.PMID:38005234 | DOI:10.3390/molecules28227512

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