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

Methionine and one carbon metabolism as a regulator of bone remodeling with fasting

Thu, 23/05/2024 - 12:00
JCI Insight. 2024 May 21:e177997. doi: 10.1172/jci.insight.177997. Online ahead of print.ABSTRACTCaloric restriction improves metabolic health, but is often complicated by bone loss. We studied bone parameters in humans during a 10-day fast and identified candidate metabolic regulators of bone turnover. P1NP, a bone formation marker, decreased within 3 days of fasting. Whereas dual-energy X-ray absorptiometry measures of bone mineral density were unchanged after 10 days of fasting, high-resolution peripheral quantitative CT demonstrated remodeling of bone microarchitecture. Pathway analysis of longitudinal metabolomics data identified one-carbon metabolism as fasting-dependent. In cultured osteoblasts, we tested the functional significance of one-carbon metabolites modulated by fasting, finding that methionine - which surged after 3 days of fasting - impacted markers of osteoblast cell state in a concentration dependent manner, in some instances exhibiting a U-shaped response with both low and high concentrations driving putative anti-bone responses. Administration of methionine to mice for 5 days recapitulated some fasting effects on bone, including a reduction in serum P1NP. In conclusion, a 10-day fast in humans led to remodeling of bone microarchitecture, potentially mediated by a surge in circulating methionine. These data support an emerging model that points to a window of optimal methionine exposure for bone health.PMID:38780544 | DOI:10.1172/jci.insight.177997

Buyang Huanwu Decoction Alleviates Atherosclerosis by Regulating gut Microbiome and Metabolites in Apolipoprotein E-deficient Mice fed with High-fat Diet

Thu, 23/05/2024 - 12:00
Journal of physiological investigation. 2024 Mar 1;67(2):88-102. doi: 10.4103/ejpi.EJPI-D-23-00031. Epub 2024 Apr 30.ABSTRACTThe traditional Chinese herbal prescription Buyang Huanwu decoction (BHD), effectively treats atherosclerosis. However, the mechanism of BHD in atherosclerosis remains unclear. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. An atherosclerotic model was established in apolipoprotein E-deficient mice fed high-fat diet, and BHD was administered through gavage for 12 weeks at 8.4 g/kg/d and 16.8 g/kg/d. The atherosclerotic plaque size, composition, serum lipid profile, and inflammatory cytokines, were assessed. Mechanistically, metabolomic and microbiota profiles were analyzed by liquid chromatography-mass spectrometry and 16S rRNA gene sequencing, respectively. Furthermore, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Atherosclerotic mice treated with BHD exhibited reduced plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. Nine perturbed serum metabolites were significantly restored along with the relative abundance of microbiota at the family and genus levels but not at the phylum level. Gut microbiome improvement was strongly negatively correlated with improved metabolite levels. BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites.PMID:38780293 | DOI:10.4103/ejpi.EJPI-D-23-00031

<em>Lactobacillus-</em>derived protoporphyrin IX and SCFAs regulate the fiber size via glucose metabolism in the skeletal muscle of chickens

Thu, 23/05/2024 - 12:00
mSystems. 2024 May 23:e0021424. doi: 10.1128/msystems.00214-24. Online ahead of print.ABSTRACTThe gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.PMID:38780275 | DOI:10.1128/msystems.00214-24

Human-derived fecal microbiota transplantation alleviates social deficits of the BTBR mouse model of autism through a potential mechanism involving vitamin B<sub>6</sub> metabolism

Thu, 23/05/2024 - 12:00
mSystems. 2024 May 23:e0025724. doi: 10.1128/msystems.00257-24. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.PMID:38780265 | DOI:10.1128/msystems.00257-24

3α-Hydroxylup-20(29)-ene-23,28-dioic Acid as a Phytogenic Chemical Marker for Authenticating <em>Schefflera octophylla</em> (Lour.) Harms Monofloral Honey

Thu, 23/05/2024 - 12:00
J Agric Food Chem. 2024 May 23. doi: 10.1021/acs.jafc.4c02186. Online ahead of print.ABSTRACTThe monofloral honey from Schefflera octophylla (Lour.) Harms (MH-Sco) are of high economic value due to their rarity and potential medicinal benefits. However, the limited investigations on the relationship of phytogenic components between the plant S. octophylla (P-Sco) and MH-Sco have an impact on MH-Sco authentication. Herein, the tentative phytogenic markers of MH-Sco were screened by comparing the metabolites of MH-Sco obtained by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS)-based untargeted metabolomics with the identified phytogenic chemicals from P-Sco. Combined with the mass and NMR spectral information, 3α-hydroxylup-20(29)-ene-23,28-dioic acid (HLEDA) was finally identified as the phytogenic marker of MH-Sco. A targeted ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS)-based method was established and validated based on the purified monomer standard to measure HLEDA levels in honey samples. HLEDA determined in MH-Sco was with the content from 0.303 to 0.440 mg/kg, while HLEDA was absent in honey samples from other botanical origins, indicating the reliability of HLEDA as a chemical marker in MH-Sco authentication. This study provides the theoretical basis and industry guidance for honey quality control for commercial consumption.PMID:38779705 | DOI:10.1021/acs.jafc.4c02186

Black raspberry-mediated metabolic changes in patients with familial adenomatous polyposis associated with rectal polyp regression

Thu, 23/05/2024 - 12:00
Food Front. 2024 Mar;5(2):259-266. doi: 10.1002/fft2.323. Epub 2024 Jan 29.ABSTRACTFamilial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.PMID:38779578 | PMC:PMC11107796 | DOI:10.1002/fft2.323

An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients

Thu, 23/05/2024 - 12:00
Front Cell Infect Microbiol. 2024 May 8;14:1366192. doi: 10.3389/fcimb.2024.1366192. eCollection 2024.ABSTRACTBACKGROUND: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches.METHODS: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis.RESULTS: In the UC cohort, we reported the increase of Streptococcus, Bifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions.CONCLUSION: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC.PMID:38779566 | PMC:PMC11109417 | DOI:10.3389/fcimb.2024.1366192

Shifts in the functional capacity and metabolite composition of the gut microbiome during recovery from enteric infection

Thu, 23/05/2024 - 12:00
Front Cell Infect Microbiol. 2024 May 8;14:1359576. doi: 10.3389/fcimb.2024.1359576. eCollection 2024.ABSTRACTWhile enteric pathogens have been widely studied for their roles in causing foodborne infection, their impacts on the gut microbial community have yet to be fully characterized. Previous work has identified notable changes in the gut microbiome related to pathogen invasion, both taxonomically and genetically. Characterization of the metabolic landscape during and after enteric infection, however, has not been explored. Consequently, we investigated the metabolome of paired stools recovered from 60 patients (cases) during and after recovery from enteric bacterial infections (follow-ups). Shotgun metagenomics was applied to predict functional microbial pathways combined with untargeted metametabolomics classified by Liquid Chromatography Mass Spectrometry. Notably, cases had a greater overall metabolic capacity with significantly higher pathway richness and evenness relative to the follow-ups (p<0.05). Metabolic pathways related to central carbon metabolism, amino acid metabolism, and lipid and fatty acid biosynthesis were more highly represented in cases and distinct signatures for menaquinone production were detected. By contrast, the follow-up samples had a more diverse metabolic landscape with enhanced richness of polar metabolites (p<0.0001) and significantly greater richness, evenness, and overall diversity of nonpolar metabolites (p<0.0001). Although many metabolites could not be annotated with existing databases, a marked increase in certain clusters of metabolites was observed in the follow-up samples when compared to the case samples and vice versa. These findings suggest the importance of key metabolites in gut health and recovery and enhance understanding of metabolic fluctuations during enteric infections.PMID:38779558 | PMC:PMC11109446 | DOI:10.3389/fcimb.2024.1359576

Eicosapentaenoic acid increases proportion of type 1 muscle fibers through PPARδ and AMPK pathways in rats

Thu, 23/05/2024 - 12:00
iScience. 2024 Apr 26;27(6):109816. doi: 10.1016/j.isci.2024.109816. eCollection 2024 Jun 21.ABSTRACTMuscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance.PMID:38779480 | PMC:PMC11108975 | DOI:10.1016/j.isci.2024.109816

New insights into the antibiofilm activity and mechanism of Mannosylerythritol Lipid-A against <em>Listeria monocytogenes</em> EGD-e

Thu, 23/05/2024 - 12:00
Biofilm. 2024 May 11;7:100201. doi: 10.1016/j.bioflm.2024.100201. eCollection 2024 Jun.ABSTRACTListeria monocytogenes is one of the leading causative agents of foodborne disease outbreaks worldwide. Herein, the antibiofilm effect and mechanism of Mannosylerythritol Lipid-A against L. monocytogenes EGD-e is reported for the first time. MEL-A effectively attenuated biofilm formation while reducing the viability and motility of bacteria within the biofilm in the early stage, and influenced bacterial adhesion by affecting the secretion of extracellular polysaccharides and eDNA. RT-qPCR revealed that MEL-A significantly suppressed the expression of genes involved in flagellar movement and virulence. Untargeted LC-MS metabolomics indicated that MEL-A affected the fluidity and permeability of cell membranes by significantly upregulating unsaturated fatty acids, lipids and glycoside metabolites, and affected protein biosynthesis, nucleotide metabolism and DNA synthesis and repair by significantly downregulating amino acid metabolism and nucleic acid metabolism. These pathways may constitute the key targets of biofilm formation inhibition by MEL-A. Furthermore, MEL-A showed good removal effects on mature biofilms under different temperatures, different materials and milk. Our data indicated that MEL-A could be used as a novel antibiofilm agent to improve food safety. Our study provides new insights into the possible inhibitory mechanism of MEL-A and the response of L. monocytogenes EGD-e to MEL-A.PMID:38779407 | PMC:PMC11108854 | DOI:10.1016/j.bioflm.2024.100201

Editorial: Pulmonary hypertension: from bench to bedside

Thu, 23/05/2024 - 12:00
Front Physiol. 2024 May 8;15:1421654. doi: 10.3389/fphys.2024.1421654. eCollection 2024.NO ABSTRACTPMID:38779320 | PMC:PMC11109390 | DOI:10.3389/fphys.2024.1421654

Efficacy of Shenglin decoction in preventing acute severe lymphocytopenia in patients with non-small cell lung cancer undergoing concurrent chemoradiotherapy: a study protocol for a randomized controlled trial

Thu, 23/05/2024 - 12:00
Front Oncol. 2024 May 8;14:1378662. doi: 10.3389/fonc.2024.1378662. eCollection 2024.ABSTRACTBACKGROUND: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL.METHODS: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms.DISCUSSION: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT.TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).PMID:38779093 | PMC:PMC11109395 | DOI:10.3389/fonc.2024.1378662

Current Knowledge on the Preparation and Benefits of Cruciferous Vegetables as Relates to In Vitro, In Vivo, and Clinical Models of Inflammatory Bowel Disease

Thu, 23/05/2024 - 12:00
Curr Dev Nutr. 2024 Apr 17;8(5):102160. doi: 10.1016/j.cdnut.2024.102160. eCollection 2024 May.ABSTRACTInflammatory bowel disease is a chronic condition with a significant economic and social burden. The disease is complex and challenging to treat because it involves several pathologies, such as inflammation, oxidative stress, dysbiosis, and intestinal damage. The search for an effective treatment has identified cruciferous vegetables and their phytochemicals as potential management options for inflammatory bowel disease because they contain prebiotics, probiotics, and anti-inflammatory and antioxidant metabolites essential for a healthy gut. This critical narrative style review provides a robust insight into the pharmacological effects and benefits of crucifers and their documented bioactive compounds in in vitro and in vivo models, as well as clinical inflammatory bowel disease. The review highlights the significant impact of crucifer preparation and the presence of glucosinolates, isothiocyanates, flavonoids, and polyphenolic compounds, which are essential for the anti-inflammatory and antioxidative benefits of cruciferous vegetables, as well as their ability to promote the healthy microbial community and maintain the intestinal barrier. This review may serve as a viable nutritional guide for future research on methods and features essential to developing experiments, preventions, and treatments for inflammatory bowel disease. There is limited clinical information and future research may utilize current innovative tools, such as metabolomics, for adequate knowledge and effective translation into clinical therapy.PMID:38779039 | PMC:PMC11108850 | DOI:10.1016/j.cdnut.2024.102160

LC-MS-based rheumatoid arthritis serum metabolomics reveals the role of deoxyinosine in attenuating collagen-induced arthritis in mice

Thu, 23/05/2024 - 12:00
Heliyon. 2024 May 8;10(10):e30903. doi: 10.1016/j.heliyon.2024.e30903. eCollection 2024 May 30.ABSTRACTRheumatoid arthritis (RA) is a persistent autoimmune condition with no identified cure currently. Recently, scientists have applied metabolomics to investigate altered metabolic profiles and unique diseases-associated metabolic signatures. Herein, we applied metabolomics approach to analyze serum samples of 41 RA patients and 42 healthy controls (HC) with the aim to characterize RA patients' metabolic profile, investigate related underlying pathological processes, and identify target metabolites. By utilizing ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry, we found 168 proposed metabolites and 45 vital metabolic pathways. Our analysis revealed that deoxyinosine (DI), a metabolite of the purine metabolic pathway, was the most significant reduced metabolite in RA patients. Furthermore, through targeted detection, we confirmed lower concentration of DI in RA patients' peripheral blood. Moreover, DI inhibited lipopolysaccharide-induced inflammation both in vitro and in vivo. We further assessed DI's therapeutic potential in a collagen-induced arthritis (CIA) murine model. The results revealed that DI attenuated CIA, as evidenced by significantly lowered clinical scores of arthritis, alleviated joint swelling, and mitigated bone destruction. Moreover, we elucidated the underlying mechanism by which DI increased the population of myeloid-derived suppressor cells (MDSCs) and suppressed the proliferation of induced T cells. Collectively, these findings suggested that DI potentially ameliorated RA by inducing immunosuppressive MDSCs. The study provides key observations on RA pathogenesis and may contribute to developing novel therapeutic strategies for this debilitating condition.PMID:38778995 | PMC:PMC11108858 | DOI:10.1016/j.heliyon.2024.e30903

Metabolomics datasets in the Born in Bradford cohort

Thu, 23/05/2024 - 12:00
Wellcome Open Res. 2020 Nov 5;5:264. doi: 10.12688/wellcomeopenres.16341.1. eCollection 2020.ABSTRACTMetabolomics is the quantification of small molecules, commonly known as metabolites. Collectively, these metabolites and their interactions within a biological system are known as the metabolome. The metabolome is a unique area of study, capturing influences from both genotype and environment. The availability of high-throughput technologies for quantifying large numbers of metabolites, as well as lipids and lipoprotein particles, has enabled detailed investigation of human metabolism in large-scale epidemiological studies. The Born in Bradford (BiB) cohort includes 12,453 women who experienced 13,776 pregnancies recruited between 2007-2011, their partners and their offspring. In this data note, we describe the metabolomic data available in BiB, profiled during pregnancy, in cord blood and during early life in the offspring. These include two platforms of metabolomic profiling: nuclear magnetic resonance and mass spectrometry. The maternal measures, taken at 26-28 weeks' gestation, can provide insight into the metabolome during pregnancy and how it relates to maternal and offspring health. The offspring cord blood measurements provide information on the fetal metabolome. These measures, alongside maternal pregnancy measures, can be used to explore how they may influence outcomes. The infant measures (taken around ages 12 and 24 months) provide a snapshot of the early life metabolome during a key phase of nutrition, environmental exposures, growth, and development. These metabolomic data can be examined alongside the BiB cohorts' extensive phenotype data from questionnaires, medical, educational and social record linkage, and other 'omics data.PMID:38778888 | PMC:PMC11109709 | DOI:10.12688/wellcomeopenres.16341.1

Low-Temperature Plasma Pretreatment Enhanced Cholesterol Detection in Brain by Desorption Electrospray Ionization-Mass Spectrometry Imaging

Thu, 23/05/2024 - 12:00
J Am Soc Mass Spectrom. 2024 May 22. doi: 10.1021/jasms.4c00045. Online ahead of print.ABSTRACTCholesterol is a primary lipid molecule in the brain that contains one-fourth of the total body cholesterol. Abnormal cholesterol homeostasis is associated with neurodegenerative disorders. Mass spectrometry imaging (MSI) technique is a powerful tool for studying lipidomics and metabolomics. Among the MSI techniques, desorption electrospray ionization-MSI (DESI-MSI) has been used advantageously to study brain lipidomics due to its soft and ambient ionization nature. However, brain cholesterol is poorly ionized. To this end, we have developed a new method for detecting brain cholesterol by DESI-MSI using low-temperature plasma (LTP) pretreatment as an ionization enhancement. In this method, the brain sections were treated with LTP for 1 and 2 min prior to DESI-MSI analyses. Interestingly, the MS signal intensity of cholesterol (at m/z 369.35 [M + H - H2O]+) was more than 2-fold higher in the 1 min LTP-treated brain section compared to the untreated section. In addition, we detected cholesterol, more specifically excluding isomers by targeted-DESI-MSI in multiple reaction monitoring (MRM) mode and similar results were observed: the signal intensity of each cholesterol transition (m/z 369.4 → 95.1, 109.1, 135.1, 147.1, and 161.1) was increased by more than 2-fold due to 1 min LTP treatment. Cholesterol showed characteristic distributions in the fiber tract region, including the corpus callosum and anterior commissure, anterior part of the brain where LTP markedly (p < 0.001) enhanced the cholesterol intensity. In addition, the distributions of some unknown analytes were exclusively detected in the LTP-treated section. Our study revealed LTP pretreatment as a potential strategy to ionize molecules that show poor ionization efficiency in the MSI technique.PMID:38778699 | DOI:10.1021/jasms.4c00045

Multi-omics research progress in early-onset colorectal cancer

Thu, 23/05/2024 - 12:00
Zhonghua Wei Chang Wai Ke Za Zhi. 2024 May 25;27(5):447-451. doi: 10.3760/cma.j.cn441530-20240205-00058.ABSTRACTGlobally, the incidence of early-onset colorectal cancer (EOCRC) among individuals younger than 50 is escalating. Compared to late-onset colorectal cancer, EOCRC exhibits distinct clinical, pathological, and molecular features, with a higher prevalence in the left colon and rectum. However, the occurrence and development of EOCRC is a multi-factor and multi-stage evolution process, which is the result of the mutual effect of environmental, genetic and biological factors, and involves the multi-level regulation mechanism of other organisms. With the development and improvement of high-throughput sequencing technology, the application of multi-omics analysis has become an important development direction to resolve the pathogenesis of complex diseases and individualized treatment plans. This article aims to review the research progress of EOCRC at the multi-omics level, providing a theoretical foundation for earlier diagnosis and more precise treatment of this diseases.PMID:38778683 | DOI:10.3760/cma.j.cn441530-20240205-00058

Metabolomics Characterization of Disease Markers in Diabetes and Its Associated Pathologies

Thu, 23/05/2024 - 12:00
Metab Syndr Relat Disord. 2024 May 23. doi: 10.1089/met.2024.0038. Online ahead of print.ABSTRACTWith the change in lifestyle of people, there has been a considerable increase in diabetes, which brings with it certain follow-up pathological conditions, which lead to a substantial medical burden. Identifying biomarkers that aid in screening, diagnosis, and prognosis of diabetes and its associated pathologies would help better patient management and facilitate a personalized treatment approach for prevention and treatment. With the advancement in techniques and technologies, metabolomics has emerged as an omics approach capable of large-scale high throughput data analysis and identifying and quantifying metabolites that provide an insight into the underlying mechanism of the disease and its progression. Diabetes and metabolomics keywords were searched in correspondence with the assigned keywords, including kidney, cardiovascular diseases and critical illness from PubMed and Scopus, from its inception to Dec 2023. The relevant studies from this search were extracted and included in the study. This review is focused on the biomarkers identified in diabetes, diabetic kidney disease, diabetes-related development of CVD, and its role in critical illness.PMID:38778629 | DOI:10.1089/met.2024.0038

Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis

Thu, 23/05/2024 - 12:00
Gut Microbes. 2024 Jan-Dec;16(1):2353396. doi: 10.1080/19490976.2024.2353396. Epub 2024 May 22.ABSTRACTAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.PMID:38778483 | DOI:10.1080/19490976.2024.2353396

Metabolomic analysis of retinopathy stages and amputation in type 2 diabetes

Wed, 22/05/2024 - 12:00
Clin Nutr ESPEN. 2024 Jun;61:158-167. doi: 10.1016/j.clnesp.2024.03.013. Epub 2024 Mar 24.ABSTRACTBACKGROUND: Diabetic retinopathy (DR) and limb amputation are frequent complications of diabetes that cannot always be explained by blood glucose control. Metabolomics is a science that is currently being explored in the search for biomarkers or profiles that identify clinical conditions of interest.OBJECTIVE: This study aimed to analyze, using a metabolomic approach, peripheral blood samples from type 2 diabetes mellitus (DM2) individuals, compared with those with diabetic retinopathy and limb amputation.METHODS: The sample consisted of 128 participants, divided into groups: control, DM2 without DR (DM2), non-proliferative DR (DRNP), proliferative DR (DRP), and DM2 amputated (AMP). Metabolites from blood plasma were classified by spectra using nuclear magnetic resonance (NMR), and the metabolic routes of each group using metaboanalyst.RESULTS: We identified that the metabolism of phenylalanine, tyrosine, and tryptophan was discriminant for the DRP group. Histidine biosynthesis, on the other hand, was statistically associated with the AMP group. The results of this work consolidate metabolites such as glutamine and citrulline as discriminating for DRP, and the branched-chain amino acids as important for DR.CONCLUSIONS: The results demonstrate the relationship between the metabolism of ketone bodies, with acetoacetate metabolite being discriminating for the DRP group and histidine being a significant metabolite in the AMP group, when compared to the DM2 group.PMID:38777429 | DOI:10.1016/j.clnesp.2024.03.013

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