Metabolomics最新文献

{"title":"Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.","authors":"Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha","doi":"10.1007/s11306-024-02089-z","DOIUrl":"10.1007/s11306-024-02089-z","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.</p><p><strong>Objective: </strong>To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.</p><p><strong>Methods: </strong>We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.</p><p><strong>Results: </strong>Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.</p><p><strong>Conclusion: </strong>Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal metabolite profiling of Streptococcus pneumoniae-associated community-acquired pneumonia.","authors":"Ilona den Hartog, Laura B Zwep, Jacqueline J Meulman, Thomas Hankemeier, Ewoudt M W van de Garde, J G Coen van Hasselt","doi":"10.1007/s11306-024-02091-5","DOIUrl":"10.1007/s11306-024-02091-5","url":null,"abstract":"<p><strong>Introduction: </strong>Longitudinal biomarkers in patients with community-acquired pneumonia (CAP) may help in monitoring of disease progression and treatment response. The metabolic host response could be a potential source of such biomarkers since it closely associates with the current health status of the patient.</p><p><strong>Objectives: </strong>In this study we performed longitudinal metabolite profiling in patients with CAP for a comprehensive range of metabolites to identify potential host response biomarkers.</p><p><strong>Methods: </strong>Previously collected serum samples from CAP patients with confirmed Streptococcus pneumoniae infection (n = 25) were used. Samples were collected at multiple time points, up to 30 days after admission. A wide range of metabolites was measured, including amines, acylcarnitines, organic acids, and lipids. The associations between metabolites and C-reactive protein (CRP), procalcitonin, CURB disease severity score at admission, and total length of stay were evaluated.</p><p><strong>Results: </strong>Distinct longitudinal profiles of metabolite profiles were identified, including cholesteryl esters, diacyl-phosphatidylethanolamine, diacylglycerols, lysophosphatidylcholines, sphingomyelin, and triglycerides. Positive correlations were found between CRP and phosphatidylcholine (34:1) (cor = 0.63) and negative correlations were found for CRP and nine lysophosphocholines (cor = - 0.57 to - 0.74). The CURB disease severity score was negatively associated with six metabolites, including acylcarnitines (tau = - 0.64 to - 0.58). Negative correlations were found between the length of stay and six triglycerides (TGs), especially TGs (60:3) and (58:2) (cor = - 0.63 and - 0.61).</p><p><strong>Conclusion: </strong>The identified metabolites may provide insight into biological mechanisms underlying disease severity and may be of interest for exploration as potential treatment response monitoring biomarker.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10914916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary habits and plasma lipid concentrations in a general Japanese population.","authors":"Mitsuharu Sato, Eiji Hishinuma, Naomi Matsukawa, Yoshiko Shima, Daisuke Saigusa, Ikuko N Motoike, Mana Kogure, Naoki Nakaya, Atsushi Hozawa, Shinichi Kuriyama, Masayuki Yamamoto, Seizo Koshiba, Kengo Kinoshita","doi":"10.1007/s11306-024-02087-1","DOIUrl":"10.1007/s11306-024-02087-1","url":null,"abstract":"<p><strong>Introduction: </strong>Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health.</p><p><strong>Objectives: </strong>As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population.</p><p><strong>Methods: </strong>We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan.</p><p><strong>Results: </strong>Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption.</p><p><strong>Conclusion: </strong>This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10914877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploratory investigation of the CSF metabolic profile of HIV in a South African paediatric cohort using GCxGC-TOF/MS.","authors":"Anicia Thirion, Du Toit Loots, Monray E Williams, Regan Solomons, Shayne Mason","doi":"10.1007/s11306-024-02098-y","DOIUrl":"10.1007/s11306-024-02098-y","url":null,"abstract":"<p><strong>Introduction: </strong> Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.</p><p><strong>Aim and objective: </strong>The aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.</p><p><strong>Results: </strong>The results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.</p><p><strong>Conclusions: </strong>This study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10907482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted Tuzzerella abundance and impaired L-glutamine levels induce Treg accumulation in ovarian endometriosis: a comprehensive multi-omics analysis.","authors":"Yichen Chen, Lingfang Ye, Jue Zhu, Liang Chen, Huan Chen, Yuhui Sun, Yishen Rong, Jing Zhang","doi":"10.1007/s11306-023-02072-0","DOIUrl":"10.1007/s11306-023-02072-0","url":null,"abstract":"<p><strong>Introduction: </strong>The microbial community plays a crucial role in the pathological microenvironment. However, the structure of the microbial community within endometriotic lesions and its impact on the microenvironment is still limited.</p><p><strong>Methods: </strong>All 55 tissue samples, including ovarian ectopic (OEMs) and normal (NE) endometrium, were subjected to 16S rRNA sequencing, metabolomic and proteomic analysis.</p><p><strong>Results: </strong>We found the abundance of Tuzzerella is significantly lower in OEMs compared to NE tissue (p < 0.01). We selected samples from these two groups that exhibited the most pronounced difference in Tuzzerella abundance for further metabolomic and proteomic analysis. Our findings indicated that endometriotic lesions were associated with a decrease in L-Glutamine levels. However, proteomic analysis revealed a significant upregulation of proteins related to the complement pathway, including C3, C7, C1S, CLU, and A2M. Subsequent metabolic and protein correlation predictions demonstrated a negative regulation between L-Glutamine and C7. In vitro experiments further confirmed that high concentrations of Glutamine significantly inhibit C7 protein expression. Additionally, immune cell infiltration analysis, multiplex immunofluorescence, and multifactorial testing demonstrated a positive correlation between C7 expression and the infiltration of regulatory T cells (Tregs) in ectopic lesions, while L-Glutamine was found to negatively regulate the expression of chemotactic factors for Tregs.</p><p><strong>Conclusion: </strong>In this study, we found a clear multi-omics pathway alteration, \"Tuzzerella (microbe)-L-Glutamine (metabolite)-C7 (protein),\" which affects the infiltration of Tregs in endometriotic lesions. Our findings provide insights into endometriosis classification and personalized treatment strategies based on microbial structures.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10904428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139996787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of metabolite biomarkers for odontogenic keratocysts.","authors":"Shuai Wang, Liyuan Yu, Lin Chen, Tao Zeng, Xianghui Xing, Zheng Wei","doi":"10.1007/s11306-024-02101-6","DOIUrl":"10.1007/s11306-024-02101-6","url":null,"abstract":"<p><strong>Introduction: </strong>Odontogenic keratocysts (OKCs) are locally aggressive and have a high rate of recurrence, but the pathogenesis of OKCs is not fully understood. We aimed to investigate the serum metabolomic profile of OKCs and discover potential biomarkers.</p><p><strong>Methods: </strong>Metabolomic analysis was performed on 42 serum samples from 22 OKC patients and 20 healthy controls (HCs) using gas chromatography‒mass spectrometry to identify dysregulated metabolites in the OKC samples. LASSO regression and receiver operating characteristic (ROC) curve analyses were used to select and validate metabolic biomarkers and develop diagnostic models.</p><p><strong>Results: </strong>A total of 73 metabolites were identified in the serum samples, and 24 metabolites were dysregulated in the OKC samples, of which 4 were upregulated. Finally, a diagnostic panel of 10 metabolites was constructed that accurately diagnosed OKCs (sensitivity of 100%, specificity of 100%, area under the curve of 1.00).</p><p><strong>Conclusion: </strong>This study is the first to investigate the metabolic characteristics and potential metabolic biomarkers in the serum of OKC patients using GC‒MS. Our study provides further evidence to explore the pathogenesis of OKC.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Untargeted metabolomic, and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome.","authors":"Marwa Zafarullah, Kathleen Angkustsiri, Austin Quach, Seungjun Yeo, Blythe P Durbin-Johnson, Heather Bowling, Flora Tassone","doi":"10.1007/s11306-024-02088-0","DOIUrl":"10.1007/s11306-024-02088-0","url":null,"abstract":"<p><strong>Introduction: </strong>The chromosome 22q11.2 deletion syndrome (22q11.2DS) is characterized by a well-defined microdeletion and is associated with a wide range of brain-related phenotypes including schizophrenia spectrum disorders (SCZ), autism spectrum disorders (ASD), anxiety disorders and attention deficit disorders (ADHD). The typically deleted region in 22q11.2DS contains multiple genes which haploinsufficiency has the potential of altering the protein and the metabolic profiles.</p><p><strong>Objectives: </strong>Alteration in metabolic processes and downstream protein pathways during the early brain development may help to explain the increased prevalence of the observed neurodevelopmental phenotypes in 22q11.2DS. However, relatively little is known about the correlation of dysregulated protein/metabolite expression and neurobehavioral impairments in individuals who developed them over time.</p><p><strong>Methods: </strong>In this study, we performed untargeted metabolic and proteomic analysis in plasma samples derived from 30 subjects including 16 participants with 22q11.2DS and 14 healthy controls (TD) enrolled in a longitudinal study, aiming to identify a metabolic and protein signature informing about the underlying mechanisms involved in disease development and progression. The metabolic and proteomic profiles were also compared between the participants with 22q11.2DS with and without various comorbidities, such as medical involvement, psychiatric conditions, and autism spectrum disorder (ASD) to detect potential changes among multiple specimens, collected overtime, with the aim to understand the basic underlying mechanisms involved in disease development and progression.</p><p><strong>Results: </strong>We observed a large number of statistically significant differences in metabolites between the two groups. Among them, the levels of taurine and arachidonic acid were significantly lower in 22q11.2DS compared to the TD group. In addition, we identified 16 proteins that showed significant changes in expression levels (adjusted P < 0.05) in 22q11.2DS as compared to TD, including those involved in 70 pathways such as gene expression, the PI3K-Akt signaling pathway and the complement system. Within participants with 22q11.2DS, no significant changes in those with and without medical or psychiatric conditions were observed.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first report on plasma metabolic and proteomic profiling and on the identification of unique biomarkers in 22q11.2DS. These findings may suggest the potential role of the identified metabolites and proteins as biomarkers for the onset of comorbid conditions in 22q11.2DS. Ultimately, the altered protein pathways in 22q11.2DS may provide insights of the biological mechanisms underlying the neurodevelopmental phenotype and may provide missing molecular outcome measures in future clinical trials to assess early-diagnosis treatment and the efficacy o","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10901937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of glucose-independent and reversible metabolic pathways associated with anti-proliferative effect of metformin in liver cancer cells.","authors":"Sk Ramiz Islam, Soumen Kanti Manna","doi":"10.1007/s11306-024-02096-0","DOIUrl":"10.1007/s11306-024-02096-0","url":null,"abstract":"<p><strong>Introduction: </strong>Despite the ability of cancer cells to survive glucose deprivation, most studies on anti-cancer effect of metformin explored its impact on glucose metabolism. No study ever examined whether its anti-cancer effect is reversible. Existing evidences warrant understanding of glucose-independent non-cytotoxic anti-proliferative effect of metformin to rationalize its role in liver cancer.</p><p><strong>Objectives: </strong>Characterization of glucose-independent anti-proliferative metabolic effects of metformin as well as analysis of their reversibility in liver cancer cells.</p><p><strong>Methodology: </strong>The dose-dependent effects of metformin on HepG2 cells were examined in presence and absence of glucose. The longitudinal evolution of metabolome was analyzed along with gene and protein expression as well as their correlations with and reversibility of cellular phenotype and metabolic signatures.</p><p><strong>Results: </strong>Metformin concentrations up to 2.5 mM were found to be anti-proliferative irrespective of presence of glucose without significant increase in cytotoxicity. Apart from mitochondrial impairment, derangement of fatty acid desaturation, one-carbon, glutathione, and polyamine metabolism were associated with metformin treatment irrespective of glucose supplementation. Depletion of pantothenic acid, downregulation of essential amino acid uptake and metabolism alongside purine salvage were identified as novel glucose-independent effects of metformin. These were significantly correlated with cMyc expression and reduction in proliferation. Rescue experiments established reversibility upon metformin withdrawal and tight association between proliferation, metabotype, and cMyc expression.</p><p><strong>Conclusions: </strong>The derangement of multiple glucose-independent metabolic pathways, which are often upregulated in therapy-resistant cancer, and concomitant cMyc downregulation coordinately contribute to the anti-proliferative effect of metformin in liver cancer cells. These are reversible and may influence its therapeutic utility.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation into the role of phenolic compounds in the protection of citrus against Phyllosticta citricarpa.","authors":"Melida Mabogoane, Wilma Augustyn, Vuyelwa J Tembu, Thierry Regnier, Wilma du Plooy","doi":"10.1007/s11306-024-02095-1","DOIUrl":"10.1007/s11306-024-02095-1","url":null,"abstract":"<p><strong>Introduction: </strong>The use of chemical fungicides to combat disease has made a substantial contribution to food quality and security. Nonetheless, their applications have been limited due to environmental and health concerns, unaffordability, and the fact that pathogens have acquired resistance to some of these fungicides. Alternative eco-friendly and safe control methods should be explored. The current study investigated the influence of citrus rind phenolic compounds against Phyllosticta citricarpa infection by metabolic profiling of two citrus cultivars with varying degrees of susceptibility to infection.</p><p><strong>Methods: </strong>Chromatographic data obtained by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC) was subjected to multivariate data analysis to identify biomarkers associated with the tolerant cultivar. The identified biomarkers were tested in vitro against P. citricarpa.</p><p><strong>Results: </strong>Seville oranges, a tolerant cultivar, displayed higher levels of phenolic content and lower total sugar content, that are both associated with lower susceptibility to citrus black spot infection. The generated Principal Component Analysis (PCA) and Orthogonal Projection to Latent Structures-Discriminant Analysis (OPLS-DA) models gave an overview of the data set and identified components that may be responsible for the differences in susceptibility between the two cultivars. Candidate biomarkers associated with tolerance were identified as naringin, neoeriocitrin, bruteiridin, melitidin, and lucenin-2.</p><p><strong>Conclusion: </strong>Naringin, a major candidate biomarker was able to inhibit the growth of the pathogen at 10 000 ppm.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort.","authors":"Olle Hartvigsson, Malin Barman, Hardis Rabe, Anna Sandin, Agnes E Wold, Carl Brunius, Ann-Sofie Sandberg","doi":"10.1007/s11306-024-02092-4","DOIUrl":"10.1007/s11306-024-02092-4","url":null,"abstract":"<p><strong>Introduction: </strong>Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants' metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients, but may also provide immune maturation signals.</p><p><strong>Objectives: </strong>To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI).</p><p><strong>Methods: </strong>Untargeted metabolomics was measured using Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics.</p><p><strong>Results: </strong>Modest associations (Q2 = 0.2-0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin.</p><p><strong>Conclusion: </strong>Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}