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

<em>Bifidobacterium</em>-derived short-chain fatty acids and indole compounds attenuate nonalcoholic fatty liver disease by modulating gut-liver axis

Mon, 20/03/2023 - 11:00
Front Microbiol. 2023 Mar 1;14:1129904. doi: 10.3389/fmicb.2023.1129904. eCollection 2023.ABSTRACTEmerging evidences about gut-microbial modulation have been accumulated in the treatment of nonalcoholic fatty liver disease (NAFLD). We evaluated the effect of Bifidobacterium breve and Bifidobacterium longum on the NAFLD pathology and explore the molecular mechanisms based on multi-omics approaches. Human stool analysis [healthy subjects (n = 25) and NAFLD patients (n = 32)] was performed to select NAFLD-associated microbiota. Six-week-old male C57BL/6 J mice were fed a normal chow diet (NC), Western diet (WD), and WD with B. breve (BB) or B. longum (BL; 109 CFU/g) for 8 weeks. Liver/body weight ratio, histopathology, serum/tool analysis, 16S rRNA-sequencing, and metabolites were examined and compared. The BB and BL groups showed improved liver histology and function based on liver/body ratios (WD 7.07 ± 0.75, BB 5.27 ± 0.47, and BL 4.86 ± 0.57) and NAFLD activity scores (WD 5.00 ± 0.10, BB 1.89 ± 1.45, and BL 1.90 ± 0.99; p < 0.05). Strain treatment showed ameliorative effects on gut barrier function. Metagenomic analysis showed treatment-specific changes in taxonomic composition. The community was mainly characterized by the significantly higher composition of the Bacteroidetes phylum among the NC and probiotic-feeding groups. Similarly, the gut metabolome was modulated by probiotics treatment. In particular, short-chain fatty acids and tryptophan metabolites were reverted to normal levels by probiotics, whereas bile acids were partially normalized to those of the NC group. The analysis of gene expression related to lipid and glucose metabolism as well as the immune response indicated the coordinative regulation of β-oxidation, lipogenesis, and systemic inflammation by probiotic treatment. BB and BL attenuate NAFLD by improving microbiome-associated factors of the gut-liver axis.PMID:36937300 | PMC:PMC10014915 | DOI:10.3389/fmicb.2023.1129904

Differences in peripheral and central metabolites and gut microbiome of laying hens with different feather-pecking phenotypes

Mon, 20/03/2023 - 11:00
Front Microbiol. 2023 Mar 2;14:1132866. doi: 10.3389/fmicb.2023.1132866. eCollection 2023.ABSTRACTBACKGROUND: Feather pecking (FP) is a maladaptive behavior in laying hens that is associated with numerous physiological traits, including those involving the central neurotransmitter system and the immune system, which have been identified in many species as being regulated by the gut microbiota via the "microbiota-gut-brain" (MGB) axis. Yet, it is unknown whether and how gut microbiota influences FP by regulating multiple central neurotransmission systems and immune system.METHODS: This study was measured the prevalence of severe FP (SFP) in the commercial layer farm. The chicken flock with the highest frequency of SFP were selected for FP phenotype identification. Nontargeted metabolomics was performed to investigated the differences in the peripheral and central metabolites and 16S rDNA sequencing was performed to investigated the differences in gut microbiome of laying hens with different FP phenotypes. Correlation analysis was performed to determine the potential mechanism by which the disturbed gut microbiota may modulate host physiology and behavior.RESULTS: The results showed that pullets (12 weeks of age) showed significantly higher SFP frequencies than chicks (6 weeks of age) and adults (22 weeks of age; p < 0.05). Compared to neutrals (N), peckers (P) exhibited the stress-induced immunosuppression with the increased plasma levels of corticosterone and norepinephrine, and the decreased plasma levels of IgA, IL-1, IL-6 and tumor necrosis factor α (p < 0.05). In the cecum, the relative abundances of Bacteroides and Gemmiger were higher in the P group, while Roseburia, Ruminococcus2, Anaerostipes, Lachnospiracea_incertae_sedis and Methanobrevibacter were more enriched in the N group. Moreover, increased plasma levels of L-tryptophan, beta-tyrosine and L-histidine were found in the P group (p < 0.05). Notably, in the P group, hippocampal levels of L-tryptophan, xanthurenic acid, L-histidine and histamine were improved and showed a positive association with L-glutamic acid levels. Plasma levels of L-tryptophan, beta-tyrosine and L-histidine were both positively correlated with Bacteroides abundance but negatively correlated with Methanobrevibacter abundance.CONCLUSION: Overall, these findings suggest that the development of FP may be affected by the gut microbiota, which regulates the central glutamatergic nerve system by altering the metabolism of tryptophan, histidine and tyrosine.PMID:36937288 | PMC:PMC10017472 | DOI:10.3389/fmicb.2023.1132866

The DNA adenine methylase of <em>Salmonella</em> Enteritidis promotes their intracellular replication by inhibiting arachidonic acid metabolism pathway in macrophages

Mon, 20/03/2023 - 11:00
Front Microbiol. 2023 Mar 2;14:1080851. doi: 10.3389/fmicb.2023.1080851. eCollection 2023.ABSTRACTMacrophages can participate in immune responses by altering their metabolism, and play important roles in controlling bacterial infections. However, Salmonella Enteritidis can survive and proliferate in macrophages. After the deletion of DNA adenine methylase (Dam), the proliferation of Salmonella Enteritidis in macrophages decreased, the molecular mechanism is still unclear. After infecting macrophages with Salmonella Enteritidis wild type and dam gene deletion strains, intracellular metabolites were extracted and detected by non-targeted metabolomics and fatty acid targeted metabolomics. We found Dam had significant effects on arachidonic acid and related metabolic pathways in macrophages. The dam gene can promote the proliferation of Salmonella Enteritidis in macrophages by inhibiting the metabolic pathway of cytosolic phospholipase A2-mediated arachidonic acid production and conversion to prostaglandin E2 in macrophages, reducing the secretion of the pro-inflammatory factors IL-1β and IL-6. In addition, inhibition of arachidonic acid-related pathways in macrophages by Arachidonyl trifluoromethyl ketone could restore the proliferation of dam gene deletion strains in macrophages. This study explored the role of Dam in the process of Salmonella Enteritidis invading host cells from the perspective of host cell metabolism, and provides new insights into the immune escape mechanism of Salmonella Enteritidis.PMID:36937256 | PMC:PMC10018194 | DOI:10.3389/fmicb.2023.1080851

Differences in transcriptomic and metabolomic analyses of metabolites of shoots on tea plants of different ages and relevant regulatory network

Mon, 20/03/2023 - 11:00
Front Plant Sci. 2023 Mar 2;13:910895. doi: 10.3389/fpls.2022.910895. eCollection 2022.ABSTRACTTo investigate differences in fresh leaves of tea plants at different ages in gene expression, metabolism, and dried tea quality, and to provide references to a deep exploration on metabolite differential accumulation of fresh leaves of tea plants at different ages as well as the regulation mechanism, two groups of fresh leaves from tea plants at different ages (group JP: 20-, 200-, and 1,200-year tea plants; group YX: 50-, 100-, and 400-year tea plants) were chosen as materials, and their differences in gene expression, metabolites, and metabolic regulatory network were investigated by transcriptomics and metabolomics. A total of 12,706 differentially expressed genes (DEGs) were screened from the fresh tea leaves in the JP group, of which tea-20 vs. tea-200 had the largest number of DEGs, up to 9,041 (4,459 down-regulated genes, 4,582 up-regulated genes). A total of 644 common genes in the fresh leaves of three different ages of tea plants in the JP group were differentially expressed. A total of 8,971 DEGs were screened from the fresh leaf samples of tea plants in the YX group, of which the number of DEGs obtained in the tea-50 vs. tea-400 comparison combination was the largest with a total of 3,723 (1,722 up-regulated genes and 2,001 down-regulated genes). A total of 147 common genes were differentially expressed in the fresh leaves of three different tree ages in the YX group. The pathway enrichment analysis showed that most up-regulated DEGs and their related metabolic pathways were similar in the two groups, and that the metabolic pathways of common significant enrichment included flavonoid biosynthesis, phenylpropane biosynthesis, carbon metabolism, amino acid biosynthesis, and plant pathogen interaction. The metabolomics results showed that 72 and 117 different metabolites were screened from the JP and YX groups, respectively. Most of the different metabolites in the two groups were flavonoids, phenolic acids, amino acids, and their derivatives. Among them, the number of down-regulated flavonoids in older tea plants is generally higher than the number of up-regulated flavonoids. Moreover, according to the sensory evaluation results of dried tea of fresh leaves from tea plants of different ages, tea-1200 and tea-400 showed the highest sensory evaluation scores in their groups. With increase in plant age, the fragrance of the tea was more elegant, and it changed from a dense scent to a faint scent; the tea tasted sweet and its freshness increased, while the sense of astringency was weakened and the concentration declined. Therefore, the quality difference of tea of different tree ages is mainly related to secondary metabolic pathways such as the flavonoid biosynthesis pathway. With increase in tea age, a large number of gene expression in the flavonoid biosynthesis pathway is down-regulated, which reduces the content of bitter flavonoid substances in fresh leaves and makes tea soup more mellow.PMID:36937142 | PMC:PMC10019279 | DOI:10.3389/fpls.2022.910895

Untargeted analysis in post-COVID-19 patients reveals dysregulated lipid pathways two years after recovery

Mon, 20/03/2023 - 11:00
Front Mol Biosci. 2023 Mar 3;10:1100486. doi: 10.3389/fmolb.2023.1100486. eCollection 2023.ABSTRACTIntroduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.PMID:36936993 | PMC:PMC10022496 | DOI:10.3389/fmolb.2023.1100486

Unique metabolism and protein expression signature in human decidual NK cells

Mon, 20/03/2023 - 11:00
Front Immunol. 2023 Mar 3;14:1136652. doi: 10.3389/fimmu.2023.1136652. eCollection 2023.ABSTRACTHuman decidual natural killer (dNK) cells are a unique type of tissue-resident NK cells at the maternal-fetal interface. dNK cells are likely to have pivotal roles during pregnancy, including in maternal-fetal immune tolerance, trophoblast invasion, and fetal development. However, detailed insights into these cells are still lacking. In this study, we performed metabolomic and proteomic analyses on human NK cells derived from decidua and peripheral blood. We found that 77 metabolites were significantly changed in dNK cells. Notably, compared to peripheral blood NK (pNK) cells, 29 metabolites involved in glycerophospholipid and glutathione metabolism were significantly decreased in dNK cells. Moreover, we found that 394 proteins were differentially expressed in dNK cells. Pathway analyses and network enrichment analyses identified 110 differentially expressed proteins involved in focal adhesion, cytoskeleton remodeling, oxidoreductase activity, and fatty acid metabolism in dNK cells. The integrated proteomic and metabolomic analyses revealed significant downregulation in glutathione metabolism in dNK cells compared to pNK cells. Our data indicate that human dNK cells have unique metabolism and protein-expression features, likely regulating their function in pregnancy and immunity.PMID:36936959 | PMC:PMC10020942 | DOI:10.3389/fimmu.2023.1136652

Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (<em>Micropterus salmoides</em>) under an alternate feeding strategy

Mon, 20/03/2023 - 11:00
Front Immunol. 2023 Mar 1;14:1110696. doi: 10.3389/fimmu.2023.1110696. eCollection 2023.ABSTRACTINTRODUCTION: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant.METHODS: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days.RESULTS: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1β/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation.DISCUSSION: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.PMID:36936939 | PMC:PMC10014712 | DOI:10.3389/fimmu.2023.1110696

Relationship between gut microbiota and rheumatoid arthritis: A bibliometric analysis

Mon, 20/03/2023 - 11:00
Front Immunol. 2023 Mar 1;14:1131933. doi: 10.3389/fimmu.2023.1131933. eCollection 2023.ABSTRACTINTRODUCTION: Rheumatoid arthritis (RA) is a multifactorial autoimmune disease. Recently, growing evidence demonstrates that gut microbiota (GM) plays an important role in RA. But so far, no bibliometric studies pertaining to GM in RA have ever been published. This study attempts to depict the knowledge framework in this field from a holistic and systematic perspective based on the bibliometric analysis.METHODS: Literature related to the involvement of GM in RA was searched and picked from the Web of Science Core Collection (WOSCC) database. The annual output, cooperation, hotspots, research status and development trend of this field were analyzed by bibliometric software (VOSviewer and Bibliometricx).RESULTS: 255 original research articles and 204 reviews were included in the analysis. The articles in this field that can be retrieved in WOSCC were first published in 2004 and increased year by year since then. 2013 is a growth explosion point. China and the United States are the countries with the most contributions, and Harvard University is the affiliation with the most output. Frontiers in Immunology (total citations = 603) is the journal with the most publications and the fastest growth rate. eLife is the journal with the most citations (total citations = 1248). Scher, Jose U. and Taneja, Veena are the most productive and cited authors. The research in this field is mainly distributed in the evidence, mechanism and practical application of GM participating in RA through the analysis of keywords and documents. There is sufficient evidence to prove the close relationship between GM and RA, which lays the foundation for this field. This extended two colorful and tender branches of mechanism research and application exploration, which have made some achievements but still have broad exploration space. Recently, the keywords "metabolites", "metabolomics", "acid", "b cells", "balance", "treg cells", "probiotic supplementation" appeared most frequently, which tells us that research on the mechanism of GM participating in RA and exploration of its application are the hotspots in recent years.DISCUSSION: Taken together, these results provide a data-based and objective introduction to the GM participating in RA, giving readers a valuable reference to help guide future research.PMID:36936921 | PMC:PMC10015446 | DOI:10.3389/fimmu.2023.1131933

Editorial: Cell stress responses and metabolic reprogramming in skin diseases

Mon, 20/03/2023 - 11:00
Front Cell Dev Biol. 2023 Mar 1;11:1171812. doi: 10.3389/fcell.2023.1171812. eCollection 2023.NO ABSTRACTPMID:36936680 | PMC:PMC10014911 | DOI:10.3389/fcell.2023.1171812

Transcriptomics and metabolomics analysis reveal the anti-oxidation and immune boosting effects of mulberry leaves in growing mutton sheep

Mon, 20/03/2023 - 11:00
Front Immunol. 2023 Feb 27;13:1088850. doi: 10.3389/fimmu.2022.1088850. eCollection 2022.ABSTRACTINTRODUCTION: Currently, the anti-oxidation of active ingredients in mulberry leaves (MLs) and their forage utilization is receiving increasing attention. Here, we propose that MLs supplementation improves oxidative resistance and immunity.METHODS: We conducted a trial including three groups of growing mutton sheep, each receiving fermented mulberry leaves (FMLs) feeding, dried mulberry leaves (DMLs) feeding or normal control feeding without MLs.RESULTS: Transcriptomic and metabolomic analyses revealed that promoting anti-oxidation and enhancing disease resistance of MLs is attributed to improved tryptophan metabolic pathways and reduced peroxidation of polyunsaturated fatty acids (PUFAs). Furthermore, immunity was markedly increased after FMLs treatment by regulating glycolysis and mannose-6-phosphate pathways. Additionally, there was better average daily gain in the MLs treatment groups.CONCLUSION: These findings provide new insights for understanding the beneficial effects of MLs in animal husbandry and provide a theoretical support for extensive application of MLs in improving nutrition and health care values.PMID:36936474 | PMC:PMC10015891 | DOI:10.3389/fimmu.2022.1088850

Erratum: Omics approaches to understanding the efficacy and safety of disease-modifying treatments in multiple sclerosis

Mon, 20/03/2023 - 11:00
Front Genet. 2023 Mar 3;14:1169919. doi: 10.3389/fgene.2023.1169919. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fgene.2023.1076421.].PMID:36936438 | PMC:PMC10020709 | DOI:10.3389/fgene.2023.1169919

Clinical Biomarkers and Prediction Models for Poststroke Epilepsy: Have We Settled the Scores Yet?

Mon, 20/03/2023 - 11:00
Neurol Clin Pract. 2023 Apr;13(2):e200146. doi: 10.1212/CPJ.0000000000200146. Epub 2023 Mar 14.ABSTRACTIn an era of time-dependent reperfusion and recanalization therapy for stroke leading to improved survival, there is a growing population at risk of poststroke epilepsy (PSE). Accumulating evidence suggests a multidirectional interaction among stroke, PSE, and dementia in stroke survivors. There is no evidence to justify prophylactic antiseizure medication (ASM) to reduce these morbidities. Although several predictive molecular biomarkers and scoring models have been proposed, they remain inadequately validated for stratifying risk and indicating who will benefit from prophylactic ASM. Studies leveraging advances in genetics, metabolomics, electrophysiology, imaging, and artificial intelligence (AI) may help to discover noninvasive molecular biomarkers and easy-to-score models. These discoveries should improve our understanding of epileptogenesis in PSE and identify new pharmacologic targets. Besides, accurately identifying high-risk patients and timely initiating prophylactic ASM therapy has the potential to disrupt the feed-forward multidirectional interaction among stroke, PSE, and dementia.PMID:36936392 | PMC:PMC10022724 | DOI:10.1212/CPJ.0000000000200146

Longitudinal trajectories and determinants of plasma per- and polyfluoroalkyl substance (PFAS) levels from birth to early childhood and metabolomic associations: A pilot study in the Boston Birth Cohort

Mon, 20/03/2023 - 11:00
Precis Nutr. 2022 Jun;1(1):e00004. Epub 2022 Jun 13.ABSTRACTBACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a major public health concern worldwide due to their ubiquitous exposures, environmental persistence, maternal-to-fetal transfer, and multi-organ toxicity. This pilot study aimed to generate preliminary data to inform future studies to address data gaps in the field, including early life PFAS exposure levels, longitudinal changes, determinants, and associated metabolomic alterations in understudied Black and Hispanic children in the United States (U.S.).METHODS: This study leveraged existing biosamples and data in the Boston Birth Cohort and measured 12 legacy and emerging PFAS, including Me-PFOSA-AcOH, PFDA, PFDoA, PFHxS, PFNA, PFOA, PFOS, PFUnA, GenX, ADONA, 9Cl-PF3ONS, and PFHpS, in paired cord and early childhood plasma samples. Summary statistics and graphic plots were used to depict PFAS levels at the two time points and their longitudinal changes. Linear regression models were used to identify the early-life factors associated with cord and early childhood PFAS levels. Associations of cord PFAS with cord metabolites were explored using a metabolome-wide association approach and a targeted approach.RESULTS: This study included 39 children, of whom 25 (64%) were Black, 14 (36%) were Hispanic, and 15 (38%) were female. PFOA, PFOS, PFNA, and PFHpS were detectable in all cord and early childhood plasma samples, while GenX and ADONA were not detectable in any sample. Cord PFAS levels were weakly-to-moderately correlated with early childhood PFAS levels (r = -0.03 to 0.40). Several maternal and child factors, including gestational age, year at blood collection, and race/ethnicity, were associated with cord and early childhood PFAS levels. The metabolome-wide association study and the targeted study identified several cord metabolites that may have been affected by in utero PFAS exposure.CONCLUSIONS: This pilot study found ubiquitous exposure to multiple PFAS in cord plasma (reflects in utero exposure) and in early childhood plasma (reflects both prenatal and postnatal exposure) among U.S. Black and Hispanic children. Metabolomic analysis suggests that in utero PFAS exposures may alter fetal metabolism. Future large-scale studies are needed to replicate the findings and further examine the associations of fetal PFAS exposure with long-term health outcomes and underlying metabolic pathways.PMID:36936201 | PMC:PMC10022515

Editorial: Double-edged swords: Important factors connecting metabolic disorders and cancer development - from basic research to translational applications

Mon, 20/03/2023 - 11:00
Front Endocrinol (Lausanne). 2023 Mar 2;14:1168700. doi: 10.3389/fendo.2023.1168700. eCollection 2023.NO ABSTRACTPMID:36936168 | PMC:PMC10019277 | DOI:10.3389/fendo.2023.1168700

Untargeted metabolomics unravel serum metabolic alterations in smokers with hypertension

Mon, 20/03/2023 - 11:00
Front Physiol. 2023 Mar 2;14:1127294. doi: 10.3389/fphys.2023.1127294. eCollection 2023.ABSTRACTBackground: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis. Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index. Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.PMID:36935758 | PMC:PMC10018148 | DOI:10.3389/fphys.2023.1127294

Large-Scale metabolomics: Predicting biological age using 10,133 routine untargeted LC-MS measurements

Mon, 20/03/2023 - 11:00
Aging Cell. 2023 Mar 19:e13813. doi: 10.1111/acel.13813. Online ahead of print.ABSTRACTUntargeted metabolomics is the study of all detectable small molecules, and in geroscience, metabolomics has shown great potential to describe the biological age-a complex trait impacted by many factors. Unfortunately, the sample sizes are often insufficient to achieve sufficient power and minimize potential biases caused by, for example, demographic factors. In this study, we present the analysis of biological age in ~10,000 toxicologic routine blood measurements. The untargeted screening samples obtained from ultra-high pressure liquid chromatography-quadruple time of flight mass spectrometry (UHPLC- QTOF) cover + 300 batches and + 30 months, lack pooled quality controls, lack controlled sample collection, and has previously only been used in small-scale studies. To overcome experimental effects, we developed and tested a custom neural network model and compared it with existing prediction methods. Overall, the neural network was able to predict the chronological age with an rmse of 5.88 years (r2 = 0.63) improving upon the 6.15 years achieved by existing normalization methods. We used the feature importance algorithm, Shapley Additive exPlanations (SHAP), to identify compounds related to the biological age. Most importantly, the model returned known aging markers such as kynurenine, indole-3-aldehyde, and acylcarnitines along with a potential novel aging marker, cyclo (leu-pro). Our results validate the association of tryptophan and acylcarnitine metabolism to aging in a highly uncontrolled large-s cale sample. Also, we have shown that by using robust computational methods it is possible to deploy large LC-MS datasets for metabolomics studies to reduce the risk of bias and empower aging studies.PMID:36935524 | DOI:10.1111/acel.13813

Changes in clinic visits and diabetes and metabolic control in patients with type 2 diabetes during COVID-19 pandemic: A real world evidence

Sun, 19/03/2023 - 11:00
Prim Care Diabetes. 2023 Mar 14:S1751-9918(23)00065-7. doi: 10.1016/j.pcd.2023.03.004. Online ahead of print.ABSTRACTPURPOSE: The study aim was to evaluate the effects of public lockdown during the covid-19 pandemic on glucose and metabolic parameters as well as body weight control in type 2 diabetic patients.METHODS: This study was conducted in two outpatient Diabetes Clinics and analyzed data available in database of Diabetes Clinic. Data related to a year before covid-19 pandemic and a year during covid-19 pandemic was collected from the database and analyzed. Patients with type 2 diabetes included in the analysis if they had referred to Diabetes Clinics both before and during covid-19 pandemic. Demographic information and data about metabolic status were collected from the records of previous outpatient Clinic visits and compared RESULTS: Finally 9440 patients with mean age of 61.08 ± 11.62 referred to Diabetes Clinics in both the year before and the year of the corona pandemic. Mean FBS and HbA1c in diabetes patients reduced significantly from 155.37 ± 62.93 and 7.97 ± 1.74 before pandemic, respectively to 138.77 ± 45.39 and 7.54 ± 1.34, respectively during covid-19 outbreak. During covid-19 pandemic, all metabolic parameters including glycemic and lipid profile (except for triglyceride) and BMI (body mass index) reduced significantly statistically, but, these changes were not clinically significant. However, triglyceride level increased statistically significantly but again it was not significant clinically.CONCLUSION: During COVID-19 lockdown, glycemic and metabolic control of diabetes patients have improved significantly except for triglycerides.PMID:36935271 | DOI:10.1016/j.pcd.2023.03.004

Serum metabolomics assessment of etiological processes predisposing ketosis in water buffalo during early lactation

Sun, 19/03/2023 - 11:00
J Dairy Sci. 2023 Mar 17:S0022-0302(23)00125-X. doi: 10.3168/jds.2022-22209. Online ahead of print.ABSTRACTMetabolic disorders as ketosis are manifestations of the animal's inability to manage the increase in energy requirement during early lactation. Generally, buffaloes show a different response to higher metabolic demands than other ruminants with a lower incidence of metabolic problems, although ketosis is one of the major diseases that may decrease the productivity in buffaloes. The aim of this study was to characterize the metabolic profile of Mediterranean buffaloes (MB) associated with 2 different levels of β-hydroxybutyrate (BHB). Sixty-two MB within 50 days in milk (DIM) were enrolled and divided into 2 groups according to serum BHB concentration: healthy group (37 MB; BHB <0.70 mmol/L; body condition score: 5.00; parity: 3.78; and DIM: 30.70) and group at risk of hyperketonemia (25 MB; BHB ≥0.70 mmol/L; body condition score: 4.50; parity: 3.76; and DIM: 33.20). The statistical analysis was conducted by one-way ANOVA and unpaired 2-sample Wilcoxon tests. Fifty-seven metabolites were identified and among them, 12 were significant or tended to be significant. These metabolites were related to different metabolic changes such as mobilization of body resources, ruminal fermentations, urea cycle, thyroid hormone synthesis, inflammation, and oxidative stress status. These findings are suggestive of metabolic changes related to subclinical ketosis status that should be further investigated to better characterize this disease in the MB.PMID:36935234 | DOI:10.3168/jds.2022-22209

Rapid skin biomarker discovery using hydrogel-phase sampling followed by semi-automated liquid-phase re-extraction high-resolution mass spectrometry

Sun, 19/03/2023 - 11:00
Anal Chim Acta. 2023 Apr 29;1252:341028. doi: 10.1016/j.aca.2023.341028. Epub 2023 Feb 27.ABSTRACTA facile and rapid skin metabolomics protocol is proposed. The liquid microjunction-surface sampling probe system has been partly automated, and used in conjunction with hydrogel probes for skin metabolite analysis. A control device was built to precisely control the segmented solvent flow and analyte re-extraction into the liquid microjunction. This mode provides rapid online re-extraction of the analytes from hydrogel probes. Humectant was added to the hydrogel, and moist heat treatment was used to make the hydrogel probes rugged for sampling in the clinical setting. The developed method was validated for the analysis of choline - a putative biomarker of psoriasis. A linear relationship over six calibration levels from 3.18 × 10-5 to 3.18 × 10-4 mol m-2 has been obtained. The limit of detection was 6.6 × 10-6 mol m-2, while the recoveries range from 92 to 109%. The within-run and between-run precision were evaluated and the coefficients of variation range from 1.84 to 7.13%. Furthermore, the developed method has been used to screen patients (n = 10) and healthy participants (control group; n = 10) for psoriasis-related skin metabolites. Metabolomic profiling of the skin excretion-related signals identified potential biomarkers of psoriasis: choline, pipecolic acid, ornithine, urocanic acid, and methionine.PMID:36935144 | DOI:10.1016/j.aca.2023.341028

Regulation of arsenite toxicity in lettuce by pyrite and glutamic acid and the related mechanism

Sun, 19/03/2023 - 11:00
Sci Total Environ. 2023 Mar 17:162928. doi: 10.1016/j.scitotenv.2023.162928. Online ahead of print.ABSTRACTCompared with the effect of a single substance on arsenic plant toxicity, the effect of coexisting pyrite and natural organic matter can better reflect actual environmental conditions. In this study, the interaction between pyrite and glutamic acid in arsenite solution was explored, the influence of pyrite and glutamic acid on arsenite plant toxicity was evaluated, and the metabolic regulation mechanism of pyrite and glutamic acid on the arsenite phytotoxic effect was clarified by metabolomics analysis. Combined pyrite and glutamic acid treatment fixed more arsenic by forming chemical bonds such as AsS, AsO, and As-O-OH in culture solution and reduced inorganic arsenic levels in plants. Compared with glutamic acid alone and pyrite alone, the combined treatment reduced the inorganic arsenic concentration in plants by 4.7 % and 40.0 %, respectively. The combined treatment limited plant ROS accumulation and maintained the leaf chlorophyll content by increasing SOD synthesis. Compared with the effect of As(III) alone, the chlorophyll content increased by 15.1-21.0 % on average under the combined treatment. The combined treatment promoted the absorption of Ca, Cu, Fe, Mo and Zn in lettuce, enhanced plant adaptation to As(III) and significantly improved plant nutritional quality. Compared with glutamic acid alone, the combined treatment increased the VC, fiber and protein contents by 128.9 %, 202.8 % and 36.7 %, respectively. Metabolomics analysis indicated that in the combined treatment group, the upregulation of tyrosine, pyruvate and N metabolism increased the plant chlorophyll content. The upregulation of S metabolism increases VC synthesis in plants and inhibits ROS accumulation, thus maintaining normal plant growth and development. The upregulation of glutathione and glycine metabolism enhances plant stress resistance. This study will provide a new way to scientifically and rationally evaluate the ecological risk of arsenic and regulate its toxicity.PMID:36934948 | DOI:10.1016/j.scitotenv.2023.162928

Pages