PubMed

PLoS One. 2023 Apr 20;18(4):e0284599. doi: 10.1371/journal.pone.0284599. eCollection 2023.ABSTRACTTesting the composition, quality and authenticity of edible oils is crucial to safeguard the consumers' rights and health. The aim of our study was to identify oil-specific markers to enable the differentiation and authentication of sunflower, sesame, flaxseed and rapeseed oils, and to evaluate their antioxidant activity, total phenolic and carotenoid content. A metabolomic approach based on liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry was employed for marker discovery. Spectrophotometric method was used for determination of antioxidant activity, total phenolic and carotenoid content. 76 oil samples from the four different manufacturers were examined. We identified 13 oil-specific markers for sunflower seed oil, 8 for rapeseed oil, 5 for sesame seed oil and 3 for flaxseed oil, their retention times, accurate masses, and characteristic fragment ions are reported. The abundances of the markers for each plant species were found to vary depending on the oil producer and the product batch. Significant differences in antioxidant activity, total phenolic and carotenoid content were also observed both between oils and within oil type. The highest total phenolic content (84.03 ± 4.19 to 103.79 ± 3.67 mg of gallic acid/kg) and antioxidant activity (245.67 ± 7.59 to 297.22 ± 2.32 mg Trolox/kg) were found in sesame seed and flaxseed oils, respectively. Identified metabolic markers can be used as qualitative markers to confirm the authenticity or to detect adulterations of oils. Composition, properties and authenticity testing should be more rigorous for food products marketed as health-promoting.PMID:37079607 | DOI:10.1371/journal.pone.0284599

Metabolomics. 2023 Apr 20;19(5):44. doi: 10.1007/s11306-023-02010-0.ABSTRACTINTRODUCTION AND OBJECTIVES: Multiple sclerosis (MS) is a disease of the central nervous system associated with immune dysfunction, demyelination, and neurodegeneration. The disease has heterogeneous clinical phenotypes such as relapsing-remitting MS (RRMS) and progressive multiple sclerosis (PMS), each with unique pathogenesis. Metabolomics research has shown promise in understanding the etiologies of MS disease. However, there is a paucity of clinical studies with follow-up metabolomics analyses. This 5-year follow-up (5YFU) cohort study aimed to investigate the metabolomics alterations over time between different courses of MS patients and healthy controls and provide insights into metabolic and physiological mechanisms of MS disease progression.METHODS: A cohort containing 108 MS patients (37 PMS and 71 RRMS) and 42 controls were followed up for a median of 5 years. Liquid chromatography-mass spectrometry (LC-MS) was applied for untargeted metabolomics profiling of serum samples of the cohort at both baseline and 5YFU. Univariate analyses with mixed-effect ANCOVA models, clustering, and pathway enrichment analyses were performed to identify patterns of metabolites and pathway changes across the time effects and patient groups.RESULTS AND CONCLUSIONS: Out of 592 identified metabolites, the PMS group exhibited the most changes, with 219 (37%) metabolites changed over time and 132 (22%) changed within the RRMS group (Bonferroni adjusted P < 0.05). Compared to the baseline, there were more significant metabolite differences detected between PMS and RRMS classes at 5YFU. Pathway enrichment analysis detected seven pathways perturbed significantly during 5YFU in MS groups compared to controls. PMS showed more pathway changes compared to the RRMS group.PMID:37079261 | DOI:10.1007/s11306-023-02010-0

Blood Cancer Discov. 2023 Apr 20:OF1-OF4. doi: 10.1158/2643-3230.BCD-22-0213. Online ahead of print.ABSTRACTIn patients with multiple myeloma, completion of mRNA-based vaccination schemes failed to yield detectable SARS-CoV-2 Omicron-neutralizing antibodies and S1-RBD-specific CD8+ T cells in approximately 60% and 80% of the cases, respectively. Patients who develop breakthrough infections exhibited very low levels of live-virus neutralizing antibodies and the absence of follicular T helper cells. See related article by Azeem et al., (9) . See related article by Chang et al., (10) .PMID:37078891 | DOI:10.1158/2643-3230.BCD-22-0213

Anal Chem. 2023 Apr 20. doi: 10.1021/acs.analchem.2c05728. Online ahead of print.ABSTRACTMass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.PMID:37078759 | DOI:10.1021/acs.analchem.2c05728

Aging Cell. 2023 Apr 20:e13849. doi: 10.1111/acel.13849. Online ahead of print.ABSTRACTDecline in neuromuscular function with aging is known to be a major determinant of disability and all-cause mortality in late life. Despite the importance of the problem, the neurobiology of age-associated muscle weakness is poorly understood. In a previous report, we performed untargeted metabolomics on frail older adults and discovered prominent alteration in the kynurenine pathway, the major route of dietary tryptophan degradation that produces neurotoxic intermediate metabolites. We also showed that neurotoxic kynurenine pathway metabolites are correlated with increased frailty score. For the present study, we sought to further examine the neurobiology of these neurotoxic intermediates by utilizing a mouse model that has a deletion of the quinolinate phosphoribosyltransferase (QPRT) gene, a rate-limiting step of the kynurenine pathway. QPRT-/- mice have elevated neurotoxic quinolinic acid level in the nervous system throughout their lifespan. We found that QPRT-/- mice have accelerated declines in neuromuscular function in an age- and sex-specific manner compared to control strains. In addition, the QPRT-/- mice show premature signs of frailty and body composition changes that are typical for metabolic syndrome. Our findings suggest that the kynurenine pathway may play an important role in frailty and age-associated muscle weakness.PMID:37078472 | DOI:10.1111/acel.13849

Food Funct. 2023 Apr 20. doi: 10.1039/d3fo00775h. Online ahead of print.ABSTRACTOsteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and inflammation as the main pathological manifestations. This study aims to investigate the protective effect of prebiotics in post-traumatic osteoarthritic (PTOA) mice by modulating the gut barrier and fecal metabolomics. The results suggested that cartilage degeneration, osteophyte formation and inflammation were significantly reduced by prebiotics in PTOA mice. In addition, the gut barrier was protected by the increased expression of tight junction proteins ZO-1 and occludin in the colon. High-throughput sequencing found that 220 fecal metabolites were affected by joint trauma, 81 of which were significantly recovered after probiotic intervention, and some metabolites (valerylcarnitine, adrenic acid, oxoglutaric acid, etc.) were closely associated with PTOA. Our study demonstrates that prebiotics can delay the progression of PTOA by regulating the metabolites of the gut microbiota and protecting the gut barrier, which is expected to be an intervention method for PTOA.PMID:37077156 | DOI:10.1039/d3fo00775h

J Affect Disord. 2023 Apr 19:S0165-0327(23)00501-3. doi: 10.1016/j.jad.2023.04.039. Online ahead of print.ABSTRACTBACKGROUND: Light is a known factor affecting mood and the circadian system. Light deficit is linked to deteriorated transduction of photic information to the brain, and reduced amplitude of the perceived circadian light signaling. Retinal ganglion cells (RGCs) loss due to advanced glaucoma can be a factor compromising light perception, with consequences for circadian rhythms, sleep and mood. This study aimed to estimate associations of RGCs loss with a depression score by multiple regression, accounting for other features of glaucoma.METHODS: One hundred and fifteen patients diagnosed with primary open-angle glaucoma completed the Beck Depression Inventory II questionnaire. The damage to their RGCs was assessed by high-definition optical coherence tomography (HD-OCT) and their function by pattern electroretinogram (PERG). On fifteen of these patients, 24-h salivary melatonin patterns were determined under light-controlled laboratory conditions, and analysis of eight clock related gene polymorphisms was performed.RESULTS: Backward stepwise multiple regression revealed that the BDI score was the strongest factor that was most closely associated with the HD-OCT-based percentage of global RGCs loss (standardized coefficient, b* = 0.784, p < 0.001), surpassing other related factors, including age, intraocular pressure, visual field loss, and PERG amplitude. A high BDI score was associated with the GNβ3 825C > T polymorphism (dbSNP rs5443).LIMITATIONS: This study did not specifically address damage to intrinsically photoreceptive RGCs. The gene study is based on a limited number of volunteers.CONCLUSIONS: Depression scores are strongly associated with RGCs loss, increasing abruptly above a threshold of 15 %, supporting the hypothesis that RGCs loss in advanced glaucoma may affect non-visual photic transduction and lead to mood disturbances.PMID:37084971 | DOI:10.1016/j.jad.2023.04.039

Transl Oncol. 2023 Apr 19;33:101672. doi: 10.1016/j.tranon.2023.101672. Online ahead of print.ABSTRACTBACKGROUND: The low 5-year survival rate of oral squamous cell carcinoma (OSCC) suggests that new prognostic indicators need to be identified to aid the clinical management of patients.METHODS: Saliva samples from OSCC patients and healthy controls were collected for proteomic and metabolomic sequencing. Gene expressed profiling was downloaded from TCGA and GEO databases. After the differential analysis, proteins with a significant impact on the prognosis of OSCC patients were screened. Correlation analysis was performed with metabolites and core proteins were identified. Cox regression analysis was utilized to stratify OSCC samples based on core proteins. The prognostic predictive ability of the core protein was then evaluated. Differences in infiltration of immune cells between the different strata were identified.RESULTS: There were 678 differentially expressed proteins (DEPs), 94 intersected DEPs among them by intersecting with differentially expressed genes in TCGA and GSE30784 dataset. Seven core proteins were identified that significantly affected OSCC patient survival and strongly correlated with differential metabolites (R2 > 0.8). The samples were divided into high- and low-risk groups according to median risk score. The risk score and core proteins were well prognostic factor in OSCC patients. Genes in high-risk group were enriched in Notch signaling pathway, epithelial mesenchymal transition (EMT), and angiogenesis. Core proteins were strongly associated with the immune status of OSCC patients.CONCLUSIONS: The results established a 7-protein signatures with the hope of early detection and the capacity for risk assessment of OSCC patient prognosis. Further providing more potential targets for the treatment of OSCC.PMID:37084685 | DOI:10.1016/j.tranon.2023.101672

Crit Rev Food Sci Nutr. 2023 Apr 19:1-29. doi: 10.1080/10408398.2023.2198605. Online ahead of print.ABSTRACTPersonalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.PMID:37077157 | DOI:10.1080/10408398.2023.2198605

Biol Sex Differ. 2023 Apr 19;14(1):21. doi: 10.1186/s13293-023-00507-w.ABSTRACTBACKGROUND: The polycystic ovary syndrome (PCOS) is associated with insulin resistance, obesity and cardiometabolic comorbidities. We here challenged the hypothesis, using state-of-the art proton nuclear magnetic resonance spectroscopy metabolomics profiling, that androgen excess in women induces also a certain masculinization of intermediate metabolism that is modulated by obesity.METHODS: Participants were 53 Caucasian young adults, including 17 women with classic PCOS consisting of hyperandrogenism and ovulatory dysfunction, 17 non-hyperandrogenic women presenting with regular menses, and 19 healthy men, selected in order to be similar in terms of age and body mass index (BMI). Half of the subjects had obesity defined by a body mass index ≥ 30 kg/m2. Subjects maintained the same diet unrestricted in carbohydrates for 3 days before sampling and maintained their lifestyle and exercise patterns prior and during the study. Plasma samples were submitted to proton nuclear magnetic resonance spectroscopy metabolomics profiling.RESULTS: Obesity associated a metabolomics profile mainly characterized by increased branched chain and aromatic aminoacids. Regardless of obesity, this unfavorable profile also characterized men as compared with control women, and was shared by women with PCOS. Notably, the negative impact of obesity on metabolomics profile was restricted to women, with obese men showing no further deterioration when compared with their non-obese counterparts.CONCLUSIONS: Serum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism, and masculinization of intermediate metabolism in women with PCOS, further suggesting a role for sex and sex hormones in the regulation of intermediate metabolism.PMID:37076926 | DOI:10.1186/s13293-023-00507-w

J Transl Med. 2023 Apr 19;21(1):266. doi: 10.1186/s12967-023-04115-5.ABSTRACTBACKGROUND: The pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) has not been elucidated, but urinary microorganisms and metabolites have been shown to be closely associated with the inflammatory response of IC/BPS. Nevertheless, the exact mechanisms related to this response have not been clarified.METHODS: 16S rRNA sequencing and untargeted metabolomics techniques were used to analyse the urinary microbial and metabolite profiles of 30 IC/BPS patients and 30 healthy controls, and correlation analyses were performed to explore the mechanisms by which they might be involved in the inflammatory response of IC/BPS.RESULTS: Twenty-eight differential genera, such as Lactobacillus and Sphingomonas, were identified. A total of 44 differential metabolites such as 1,3,7-trimethyluric acid and theophylline were screened. The abundance of Lactobacillus and Escherichia-Shigella was significantly higher in the urine of female IC/BPS patients and healthy controls compared to males, while Bacteroides and Acinetobacter were lower than in males. The results of the Pearson correlation analysis suggested that differential microorganisms may influence the composition of metabolites. The Lactobacillus genus may be a protective bacterium against IC/BPS, whereas Sphingomonas may be a pathogenic factor. The differential metabolite theophylline, as an anti-inflammatory substance, may downregulate the inflammatory response of IC/BPS.CONCLUSIONS: This study revealed microbial and metabolite profiles in the urine of IC/BPS patients versus healthy controls in both males and females. We also found some microorganisms and metabolites closely related to the inflammatory response of IC/BPS, which provided directions for future aetiological and therapeutic research.PMID:37076836 | DOI:10.1186/s12967-023-04115-5

Genes Nutr. 2023 Apr 19;18(1):7. doi: 10.1186/s12263-023-00726-1.ABSTRACTThe predominant source of alcohol in the diet is alcoholic beverages, including beer, wine, spirits and liquors, sweet wine, and ciders. Self-reported alcohol intakes are likely to be influenced by measurement error, thus affecting the accuracy and precision of currently established epidemiological associations between alcohol itself, alcoholic beverage consumption, and health or disease. Therefore, a more objective assessment of alcohol intake would be very valuable, which may be established through biomarkers of food intake (BFIs). Several direct and indirect alcohol intake biomarkers have been proposed in forensic and clinical contexts to assess recent or longer-term intakes. Protocols for performing systematic reviews in this field, as well as for assessing the validity of candidate BFIs, have been developed within the Food Biomarker Alliance (FoodBAll) project. The aim of this systematic review is to list and validate biomarkers of ethanol intake per se excluding markers of abuse, but including biomarkers related to common categories of alcoholic beverages. Validation of the proposed candidate biomarker(s) for alcohol itself and for each alcoholic beverage was done according to the published guideline for biomarker reviews. In conclusion, common biomarkers of alcohol intake, e.g., as ethyl glucuronide, ethyl sulfate, fatty acid ethyl esters, and phosphatidyl ethanol, show considerable inter-individual response, especially at low to moderate intakes, and need further development and improved validation, while BFIs for beer and wine are highly promising and may help in more accurate intake assessments for these specific beverages.PMID:37076809 | DOI:10.1186/s12263-023-00726-1

Metabolomics. 2023 Apr 19;19(5):43. doi: 10.1007/s11306-023-02006-w.ABSTRACTINTRODUCTION: A ketogenic diet (KD), which is a high fat, low carbohydrate diet has been shown to inhibit the mammalian target of rapamycin (mTOR) pathway and alter the redox state. Inhibition of the mTOR complex has been associated with the attenuation and alleviation of various metabolic and- inflammatory diseases such as neurodegeneration, diabetes, and metabolic syndrome. Various metabolic pathways and signalling mechanisms have been explored to assess the therapeutic potential of mTOR inhibition. However, chronic alcohol consumption has also been reported to alter mTOR activity, the cellular redox- and inflammatory state. Thus, a relevant question that remains is what effect chronic alcohol consumption would have on mTOR activity and overall metabolism during a KD-based intervention.OBJECTIVES: The aim of this study was to evaluate the effect of alcohol and a KD on the phosphorylation of the mTORC1 target p70S6K, systemic metabolism as well as the redox- and inflammatory state in a mouse model.METHODS: Mice were fed either a control diet with/without alcohol or a KD with/without alcohol for three weeks. After the dietary intervention, samples were collected and subjected towards western blot analysis, multi-platform metabolomics analysis and flow cytometry.RESULTS: Mice fed a KD exhibited significant mTOR inhibition and reduction in growth rate. Alcohol consumption alone did not markedly alter mTOR activity or growth rate but moderately increased mTOR inhibition in mice fed a KD. In addition, metabolic profiling showed alteration of several metabolic pathways as well as the redox state following consumption of a KD and alcohol. A KD was also observed to potentially prevent bone loss and collagen degradation associated with chronic alcohol consumption, as indicated by hydroxyproline metabolism.CONCLUSION: This study sheds light on the influence that a KD alongside alcohol intake can exert on not just mTOR, but also their effect on metabolic reprogramming and the redox state.PMID:37076659 | DOI:10.1007/s11306-023-02006-w

Br J Cancer. 2023 Apr 19. doi: 10.1038/s41416-023-02256-4. Online ahead of print.ABSTRACTBACKGROUND: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity.METHODS: We performed the genomic, transcriptomic, proteomic and metabolomic analysis of 39-77 ICC tumour samples and eleven normal samples. Further, we analysed their cell proliferation and viability.RESULTS: We demonstrated that intra-tumoral heterogeneity of ICCs with distinct driver genes per case exhibited neutral evolution, regardless of their tumour stage. Upregulation of BCAT1 and BCAT2 indicated the involvement of 'Val Leu Ile degradation pathway'. ICCs exhibit the accumulation of ubiquitous metabolites, such as branched-chain amino acids including valine, leucine, and isoleucine, to negatively affect cancer prognosis. We revealed that this metabolic pathway was almost ubiquitously altered in all cases with genomic diversity and might play important roles in tumour progression and overall survival.CONCLUSIONS: We propose a novel ICC onco-metabolic pathway that could enable the development of new therapeutic interventions.PMID:37076565 | DOI:10.1038/s41416-023-02256-4

Cell Death Dis. 2023 Apr 19;14(4):278. doi: 10.1038/s41419-023-05800-5.ABSTRACTNeuronal apoptosis has been well-recognized as a critical mediator in the pathogenesis of depressive disorders. Tissue kallikrein-related peptidase 8 (KLK8), a trypsin-like serine protease, has been implicated in the pathogenesis of several psychiatric disorders. The present study aimed to explore the potential function of KLK8 in hippocampal neuronal cell apoptosis associated with depressive disorders in rodent models of chronic unpredictable mild stress (CUMS)-induced depression. It was found that depression-like behavior in CUMS-induced mice was associated with hippocampal KLK8 upregulation. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency attenuated CUMS-induced depression-like behaviors and hippocampal neuronal apoptosis. In HT22 murine hippocampal neuronal cells and primary hippocampal neurons, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce neuron apoptosis. Mechanistically, it was identified that the neural cell adhesion molecule 1 (NCAM1) may associate with KLK8 in hippocampal neurons as KLK8 proteolytically cleaved the NCAM1 extracellular domain. Immunofluorescent staining exhibited decreased NCAM1 in hippocampal sections obtained from mice or rats exposed to CUMS. Transgenic overexpression of KLK8 exacerbated, whereas KLK8 deficiency largely prevented CUMS-induced loss of NCAM1 in the hippocampus. Both adenovirus-mediated overexpression of NCAM1 and NCAM1 mimetic peptide rescued KLK8-overexpressed neuron cells from apoptosis. Collectively, this study identified a new pro-apoptotic mechanism in the hippocampus during the pathogenesis of CUMS-induced depression via the upregulation of KLK8, and raised the possibility of KLK8 as a potential therapeutic target for depression.PMID:37076499 | DOI:10.1038/s41419-023-05800-5

Cell Death Dis. 2023 Apr 19;14(4):276. doi: 10.1038/s41419-023-05791-3.ABSTRACTOmicron variants of SARS-CoV-2 have spread rapidly worldwide; however, most infected patients have mild or no symptoms. This study aimed to understand the host response to Omicron infections by performing metabolomic profiling of plasma. We observed that Omicron infections triggered an inflammatory response and innate immune, and adaptive immunity was suppressed, including reduced T-cell response and immunoglobulin antibody production. Similar to the original SARS-CoV-2 strain circulating in 2019, the host developed an anti-inflammatory response and accelerated energy metabolism in response to Omicron infection. However, differential regulation of macrophage polarization and reduced neutrophil function has been observed in Omicron infections. Interferon-induced antiviral immunity was not as strong in Omicron infections as in the original SARS-CoV-2 infections. The host response to Omicron infections increased antioxidant capacity and liver detoxification more than in the original strain. Hence, these findings suggest that Omicron infections cause weaker inflammatory alterations and immune responses than the original SARS-CoV-2 strain.PMID:37076483 | DOI:10.1038/s41419-023-05791-3

Nat Commun. 2023 Apr 19;14(1):2236. doi: 10.1038/s41467-023-37729-w.ABSTRACTBiological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, and metabolomic data and identify biological associations with four measures of epigenetic age acceleration and a human longevity phenotype comprising healthspan, lifespan, and exceptional longevity (multivariate longevity). Using transcriptomic imputation, fine-mapping, and conditional analysis, we identify 22 high confidence associations with epigenetic age acceleration and seven with multivariate longevity. FLOT1, KPNA4, and TMX2 are novel, high confidence genes associated with epigenetic age acceleration. In parallel, cis-instrument Mendelian randomization of the druggable genome associates TPMT and NHLRC1 with epigenetic aging, supporting transcriptomic imputation findings. Metabolomics Mendelian randomization identifies a negative effect of non-high-density lipoprotein cholesterol and associated lipoproteins on multivariate longevity, but not epigenetic age acceleration. Finally, cell-type enrichment analysis implicates immune cells and precursors in epigenetic age acceleration and, more modestly, multivariate longevity. Follow-up Mendelian randomization of immune cell traits suggests lymphocyte subpopulations and lymphocytic surface molecules affect multivariate longevity and epigenetic age acceleration. Our results highlight druggable targets and biological pathways involved in aging and facilitate multi-omic comparisons of epigenetic clocks and human longevity.PMID:37076473 | DOI:10.1038/s41467-023-37729-w

J Agric Food Chem. 2023 Apr 19. doi: 10.1021/acs.jafc.3c00234. Online ahead of print.ABSTRACTThe marine-derived Streptomyces sp. FIMYZ-003 strain was found to produce novel siderophores with yields negatively correlated with the iron concentration in the medium. Mass spectrometry (MS)-based metabolomics coupled with metallophore assays identified two novel α-hydroxycarboxylate-type siderophores, fradiamines C and D (3 and 4), together with two related known siderophores, fradiamines A and B (1 and 2). Their chemical structures were elucidated by nuclear magnetic resonance (NMR) and MS experiments. The annotation of a putative fra biosynthetic gene cluster enabled us to propose the biosynthetic pathway of fradiamines A-D. Furthermore, the solution-phase iron-binding activity of fradiamines was evaluated using metabolomics, confirming them as general iron scavengers. Fradiamines A-D exhibited Fe(III) binding activity equivalent to that of deferoxamine B mesylate. Growth analysis of pathogenic microbes demonstrated that fradiamine C promoted the growth of Escherichia coli and Staphylococcus aureus, but fradiamines A, B, and D did not. The results indicate that fradiamine C may serve as a novel iron carrier applicable to antibiotic delivery strategies to treat and prevent foodborne pathogens.PMID:37076425 | DOI:10.1021/acs.jafc.3c00234

PLoS One. 2023 Apr 19;18(4):e0284138. doi: 10.1371/journal.pone.0284138. eCollection 2023.ABSTRACTBACKGROUND: Plenty of studies have focused on the bile acids profile in gallstones. The objective of our systematic review is to provide a comprehensive summary about bile acids profiles in gallstones and analyzes the difference between gallstones and control group in diverse samples, determining the characteristic bile acids as the metabolite biomarkers for predicting gallstone.METHODS: EMBASE, the Cochrane Library, PubMed, Web of Science, Wanfang databases, China National Knowledge Infrastructure (CNKI), VIP Information Resource Integration Service Platform (CQVIP), and China Biology Medicine Disc (SinoMed) will be searched with the keywords of gallstones and metabolomics. The screening process will be performed strictly according to inclusion and exclusion criteria. The CONSORT checklist and the Newcastle-Ottawa Scale (NOS) will assess the risk of bias for randomized controlled trials and observational studies, respectively. The qualitative review will be conducted to summarize the bile acids profile in gallstones. The concentrations of bile acids in both case group and control group will be the primary outcomes to perform the meta-analyses.EXPECTED RESULTS: Our systematic review will find the characteristic bile acids as the candidate metabolite biomarkers which equipped potential value to predict gallstones.CONCLUSION: Expanding the current knowledge on the physiopathology of gallstones and identifying novel predictive biomarkers can help to facilitate the detection and management of gallstones. Consequently, we expect this protocol to be a reasonable method to filtrate candidate differential bile acids which have potential value to predict gallstones.PROSPERO REGISTRATION NUMBER: CRD42022339649.PMID:37075059 | DOI:10.1371/journal.pone.0284138

JAMA Psychiatry. 2023 Apr 19. doi: 10.1001/jamapsychiatry.2023.0685. Online ahead of print.ABSTRACTIMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.OBJECTIVE: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD.DESIGN, SETTING AND PARTICIPANTS: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics. Replication was sought in the PREDICT and BBMRI-NL studies. Publicly available summary statistics from a 2019 genome-wide association study of depression were used for the mendelian randomization (individuals with MDD = 59 851; control individuals = 113 154). Summary statistics for the metabolites were obtained from OpenGWAS in MRbase (n = 118 000). To evaluate the interplay of the metabolome and the gut microbiome in the pathogenesis of depression, metabolic signatures of the gut microbiome were obtained from a 2019 study performed in Dutch cohorts. Data were analyzed from March to December 2021.MAIN OUTCOMES AND MEASURES: Outcomes were lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy with the Nightingale platform.RESULTS: The study included 6811 individuals with lifetime MDD compared with 51 446 control individuals and 4370 individuals with recurrent MDD compared with 62 508 control individuals. Individuals with lifetime MDD were younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) and more often female (4447 [65%] vs 2364 [35%]) than control individuals. Metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways. Novel findings included 49 metabolites, including those involved in the tricarboxylic acid cycle (ie, citrate and pyruvate). Citrate was significantly decreased (β [SE], -0.07 [0.02]; FDR = 4 × 10-04) and pyruvate was significantly increased (β [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota. Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process but high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not.CONCLUSIONS AND RELEVANCE: The study findings showed that energy metabolism was disturbed in individuals with MDD and that the interplay of the gut microbiome and blood metabolome may play a role in lipid metabolism in individuals with MDD.PMID:37074710 | DOI:10.1001/jamapsychiatry.2023.0685