NMR-based metabolomic responses of freshwater gastropod Bellamya aeruginosa to MC-producing and non MC-producing Microcystis aeruginosa

Molluscan metabolomic analysis is essential for the understanding of the regulatory mechanism of aquatic invertebrate in response to hepatotoxic microcystins(MCs)stress.To understand the system responses of the gastropod to MC exposure,metabolomic alterations caused by two strains(MC-producing and non MC-producing)of Microcystis aeruginosa were characterized indiff erent biological matrices(hepatopancreas and muscle)of Bellamya aeruginosa(Gastropoda)using 1 H nuclear magnetic resonance(NMR)spectroscopy combined with MCs detections after exposure for 1,7,and 14 d.Although ELISA analysis showed that no MCs was detected in both tissues after non MC-producing M.aeruginosa exposure,MCs concentrations were increasing in the hepatopancreas(from 1.29±0.48μg/g to 3.17±0.11μg/g)and foot muscle(from 0.07±0.02μg/g to 0.21±0.08μg/g)after 14-d exposure of MC-producing M.aeruginosa.Meanwhile,we observed that MC induced signifi cant increase in creatine,a variety of amino acids(leucine,isoleucine,valine,threonine,alanine,methionine,glutamate,aspartate,and lysine),carboxylic acids(lactate,acetate,and D-3-hydroxybutyrate),and choline and its derivatives(phosphocholine and glycerophosphocholine)but decreased the energy substance(lipids,glucose,and glycogen)in the hepatopancreas.However,no signifi cant metabolite diff erences were observed in the muscle between MC-producing and non MC-producing cyanobacteria treated groups.These results suggest that MC exposure may cause hepatic energy expenditure accompanied with various metabolic disorders that involve lipid metabolism,protein catabolism,osmoregulation,glycolysis,glycogenolysis,and tricarboxylic acid(TCA)cycle.Moreover,metabolic perturbation was aggravated as the level of accumulated MCs raised over time in the MC-producing cyanobacteria treatment.These fi ndings indicated that MCs accumulation might lead to oxidative-stress-mediated damage of mitochondria functions.

NMR-based metabolomics pro!le analysis in understanding metabolic variations of Bra LTP1-overexpressing Brassica napus

BraLTP1 is an important member of lipid transfer protein family in Brassica napus.The aim of current study was to detect, classify and follow variations in metabolite profiling of B. napus with overexpression of BraLTP1. In this study, metabolic change in leaves of BraLTP1-overexpressing B. napus plants (BraLTP1-22) and negative control (BraLTP1-22N) was investigated using nuclear magnetic resonance (NMR). Statistical strategy of principle component analysis (PCA) was performed to identify related difference metabolites. PCA score plots indicated not only high reproducibility of various treatments, but also significant difference of metabolite levels between different treatments. PCA loading plots indicated main responsible metabolites and a total of 50 metabolites were quantitatively determined. A wide range of metabolites were detected due to BraLTP1 overexpression,including biosynthesis and metabolism of sugars, amino acids, ammoniums compounds and organic acids. Furthermore, concentrations of 17 amino acids were determined for other set of samples by amino acids component analysis assay. The link between metabolite variations and phenotype were also discussed in BraLTP1-overexpressing B. napus.This work will help to gain insight into BraLTP1 function in B. napus in metabolism.

Integration of 1H-NMR-Based Metabolomics Approach with Traditional Chinese Pulse Diagnosis to Evaluate the Qi-Enhancing Activity of Herbal Tea

Human metabolism is intricately linked to an individual’s health status. Regardless of living habits, it will be reflected in the metabolic characteristics of urine. The utilization of the 1H NMR-based metabolomics method has enabled examine the metabolomic changes in urine under various physiology conditions, providing valuable insights into metabolites. In this particular study, volunteers were divided into two groups based on the strength of their spleen pulses, using the pulse diagnosis method employed in traditional Chinese medicine. Subsequently, their urine samples were analyzed, revealing notable variances in urea, creatinine, citric acid, succinic acid, trimethylamine-N-oxide (TMAO), alanine, hippuric acid, and glycine between the two groups. Interestingly, individuals with weak spleen pulses showed significant improvements after consuming herbal tea. Furthermore, we conducted LC-MS analysis on herbal tea and performed adenosine triphosphate (ATP) activity tests on the C2C12 mouse skeletal muscle cell line. The results indicated that within a reasonable concentration range, exposure to herbal tea led to an increase in the mitochondrial ATP production capacity of C2C12 cells. These findings shed light on the relationship between traditional Chinese medicine pulse diagnosis and urine metabolites, highlighting their potential as non-invasive and straightforward health assessment indicators. They can aid in the preliminary determination of necessary dietary and lifestyle changes to enhance overall bodily health.

Application of ~1H NMR-based metabolomics for discrimination of different parts and development of a new processing workflow for Cistanche deserticola

Cistanche deserticola(CD) is one of the two authoritative source plants of Cistanches Herba, a well-known medicinal plant. Herein,~1H NMR spectroscopy was employed to characterize the chemical profile and to distinguish the different parts, as well as to propose a new processing workflow for CD.Signal assignment was achieved by multiple one and two dimensional NMR spectroscopic techniques in combination with available databases and authentic compounds. The upper parts of the plant were distinguished from the lower parts by combining ~1H NMR spectroscopic dataset with multivariate statistical analysis. A new processing method that hyphenated steaming with freeze-drying, was demonstrated to be superior to either steaming coupled with oven-drying or direct freeze-drying via holistic ~1H NMR-based metabolomic characterization. Phenylethanoid glycosides, mainly echinacoside and acteoside, were screened out and confirmed as the chemical markers responsible for exhibiting the superiority of the new processing workflow, whereas serial primary metabolites, especially carbohydrates and tricarboxylic acid cycle metabolites, were found as the primary molecules governing the discrimination between the upper and lower parts of the plant. Collectively,~1H NMR spectroscopy was demonstrated as a versatile analytical tool to characterize the chemical profile and to guide the indepth exploitation of CD by providing comprehensive qualitative and quantitative information.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Review on analytical technologies and applications in metabolomics

Over the past decade,the swift advancement of metabolomics can be credited to significant progress in technologies such as mass spectrometry,nuclear magnetic resonance,and multivariate statistics.Currently,metabolomics garners widespread application across diverse fields including drug research and development,early disease detection,toxicology,food and nutrition science,biology,prescription,and chinmedomics,among others.Metabolomics serves as an effective characterization technique,offering insights into physiological process alterations in vivo.These changes may result from various exogenous factors like environmental conditions,stress,medications,as well as endogenous elements including genetic and protein-based influences.The potential scientific outcomes gleaned from these insights have catalyzed the formulation of innovative methods,poised to further broaden the scope of this domain.Today,metabolomics has evolved into a valuable and widely accepted instrument in the life sciences.However,comprehensive reviews focusing on the sample preparation and analytical methodologies employed in metabolomics within the life sciences are surprisingly scant.This review aims to fill that gap,providing an overview of current trends and recent advancements in metabolomics.Particular emphasis is placed on sample preparation,sophisticated analytical techniques,and their applications in life science research.

Metabolomics for the diagnosis of bladder cancer: A systematic review

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

Metabolomic-based analysis reveals bile acid-mediated ovarian failure induced by low temperature in zebrafish

As ectotherms, fish are highly sensitive to temperature fluctuations, which can profoundly impact their reproductive cycles. In this study, we investigated the fertility and histological characteristics of zebrafish(Danio rerio) ovaries exposed to a temperature gradient ranging from the thermopreferendum temperature of the species,27℃, to lower temperatures of 22℃, 20℃, and 13℃ over a period of two weeks. Comparative metabolomic(six biological replicates for each temperature) and transcriptomic(four biological replicates for each temperature) analyses were conducted under the four temperature conditions. Results indicated that lower temperatures inhibited oocyte development and differential metabolites were involved in steroid hormone production,antioxidant function, and lipid and protein catabolism.Disrupted reproductive hormones, increased proteolysis,and lipid degradation significantly impeded oocyte development and egg maturation. Notably, a significant increase in bile acid content was noted in the ovaries of the cold-treated fish, indicating that bile acids play a critical role in ovarian failure. Overall, these findings provide valuable insights into the mechanisms governing the reproductive response of fish to cold stress.

Metabolomic Analysis in Saliva and Different Brain Regions of Older Mice with Postoperative Delirium Behaviors

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers.Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples.Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively.“Pyruvate”“alpha-linolenic acid”and“2-oleoyl-1-palmitoy-snglycero-3-phosphocholine”are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine.Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

Reveal the pharmacodynamic substances and mechanism of an edible medicinal plant Rhodiola crenulate in DSS-induced colitis through plasma pharmacochemistry and metabolomics

Rhodiola crenulate is the edible medicinal herbal medicine widely used for altitude sickness in China.Interestingly,our previous work has found that R.crenulate extract(RCE)could significantly improve the pathology associated with dextran sulfate sodium-induced colitis.Thus,the current research aims to reveal the pharmacodynamic material basis of RCE,as well as its mechanism against colitis.The chemical characterization of RCE was performed by UHPLC-HR-MS,through which a total of 88 constituents were identified.Meanwhile,our results also found 29 constituents absorbed into blood and 8 metabolized absorbable compounds.The decreased flavonoids prototype and the elevated sulfated products of phenols were observed under pathophysiological conditions of colitis.The metabolomics study revealed that colitis caused the alternation of fatty acid metabolism,steroid hormone biosynthesis and bile acid metabolism.Correspondingly,RCE could prevent colitis by improving fatty acid metabolism and secondary bile acid metabolism.

Global status and trends of metabolomics in diabetes: A literature visualization knowledge graph study

BACKGROUND Diabetes is a metabolic disease characterized by hyperglycemia,which has increased the global medical burden and is also the main cause of death in most countries.AIM To understand the knowledge structure of global development status,research focus,and future trend of the relationship between diabetes and metabolomics in the past 20 years.METHODS The articles about the relationship between diabetes and metabolomics in the Web of Science Core Collection were retrieved from 2002 to October 23,2023,and the relevant information was analyzed using CiteSpace6.2.2R(CiteSpace),VOSviewer6.1.18(VOSviewer),and Bibliometrix software under R language.RESULTS A total of 3123 publications were included from 2002 to 2022.In the past two decades,the number of publications and citations in this field has continued to increase.The United States,China,Germany,the United Kingdom,and other relevant funds,institutions,and authors have significantly contributed to this field.Scientific Reports and PLoS One are the journals with the most publications and the most citations.Through keyword co-occurrence and cluster analysis,the closely related keywords are"insulin resistance","risk","obesity","oxidative stress","metabolomics","metabolites"and"biomarkers".Keyword clustering included cardiovascular disease,gut microbiota,metabonomics,diabetic nephropathy,molecular docking,gestational diabetes mellitus,oxidative stress,and insulin resistance.Burst detection analysis of keyword depicted that"Gene","microbiota","validation","kidney disease","antioxidant activity","untargeted metabolomics","management",and"accumulation"are knowledge frontiers in recent years.CONCLUSION The relationship between metabolomics and diabetes is receiving extensive attention.Diabetic nephropathy,diabetic cardiovascular disease,and kidney disease are key diseases for future research in this field.Gut microbiota,molecular docking,and untargeted metabolomics are key research directions in the future.Antioxidant activity,gene,validation,mass spectrometry,management,and accumulation are at the forefront of knowledge frontiers in this field.

Analysis of flavor and widely metabolomics differences in black sesame before and after processing

The objective of this study was to determine the differences of aroma and taste in three black sesame originsbefore and after processing via flavor and widely metabolomics.By analyzing the sensory characteristics and metabolites of raw and treated black sesame from China,Vietnam,and Myanmar,treated Chinese sesame have the most significant change in hardness after thermal processing,low viscosity and was easy to chew.The electronic nose could distinguish between raw and treated sesame due to the aroma distribution.The reason of treated sesame from China was“fragrant”is due to the highest content(2545.50μg/kg)of total pyrazines including 2,5-dimethylpyrazine,2-ethyl-5-methylpyrazine,2,3,5-trimethylpyrazine,3-ethyl-2,5-dimethylpyrazine.933 metabolites were detected via a wide targeted metabolomics in the taste of raw and treated sesame.Based on the analysis of metabolites related to bitterness,145 substances were selected.The main bitter contributors may be amino acids,dipeptides and organic acids.

Metabolomic Analysis of the Anthocyanins Associated with Different Colors of Cymbidium goeringii in Guizhou, China

Cymbidium goeringii is an economically important ornamental plant,and flower color is one of the main features of C.goeringii that contributes to its high economic value.To clarify the molecular mechanisms underlying the role of anthocyanins in mediating differences in color among varieties,liquid chromatography–tandem mass spectrometry was used to perform anthocyanin-targeted metabolomics of seven C.goeringii varieties,including‘Jin Qian Yuan’(JQY),‘Jin Xiu Qian Yuan’(JXQY),‘Miao Jiang Su Die’(MJSD),‘Qian Ming Su’(QMS),‘Shi Chan’(SC),and‘Yang Ming Su’(YMS),as well as the C.goeringii.We detected 64 anthocyanins,including cyanidins,delphinidins,malvidins,pelargonidins,peonidins,petunidins,procyanidins,and flavonoids.We identified six shared differentially accumulated metabolites(DAMs),including cyanidin-3-O-rutinoside,delphinidin-3-Osophoroside,pelargonidin-3-O-rutinoside,peonidin-3-O-(6-O-malonyl-beta-D-glucoside),peonidin-3-Osophoroside,and chalcone.Most DAMs were enriched in the anthocyanin biosynthesis pathway.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed metabolites were significantly enriched in the anthocyanin biosynthesis pathway.Analysis of the content of differentially expressed metabolites indicated that peonidin-3-O-(6-O-malonyl-beta-D-glucoside)was the key metabolite underlying color differences among C.goeringii varieties.Procyanidin B2,pelargonidin-3-O-galactoside,and naringenin might also affect the color formation of JQY and QMS,SC,and MJSD,respectively.The results of this study shed light on the metabolic mechanism underlying flower color differences in C.goeringii at the molecular level.Our findings will aid future studies of the mechanism of flower color regulation in C.goeringii and have implications for the breeding of new varieties.

Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Combined proteomic and metabolomic studies on the liver of Amur sturgeon Acipenser schrenckii under titanium dioxide nanoparticle exposure

Nanomaterials,particularly titanium dioxide nanoparticles(TiO_(2)-NPs),are extensively utilized across various industries.However,their environmental release has raised concerns regarding their potential ecological and environmental impacts.The reproductive toxicity of TiO_(2)-NPs in fish species has attracted considerable attention,yet conflicting research outcomes have been reported.We investigated the effects of TiO_(2)-NPs exposure on the liver of juvenile Amur sturgeon Acipenser schrenckii using label-free proteomic and untargeted metabolomic analyses.The experiment included a control group and three groups exposed to different concentrations of TiO_(2)-NPs(low,TL;medium,TM;high,TH).Compared to the control group,9,19,and 25 proteins and 35,73,and 158 metabolites were differentially expressed in the TH,TM,and TL TiO_(2)-NP-exposed groups,respectively.The differentially expressed genes(DEGs)were enriched in the Kyoto Encyclopedia for Genes and Genomes(KEGG)pathways related to glycolysis and gluconeogenesis.Moreover,among the 126 correlated proteins,the most enriched pathways were associated with endocytosis and protein processing in the endoplasmic reticulum.Notably,syringic acid was significantly downregulated across all three TiO_(2)-NP-exposed groups.To obtain a comprehensive overview of the TiO_(2)-NP-induced expression changes,a co-regulated network of proteins and metabolites associated with TiO_(2)-NPs exposure was constructed.Exposure to TiO_(2)-NPs led to enrichment and alteration of pathways related to immune responses,including endocytosis,protein processing in the endoplasmic reticulum,and peroxisome proliferator-activated receptor(PPAR)signaling.In conclusion,our findings indicate that exposure to TiO_(2)-NPs might disrupt glucose metabolism and induce immune responses,thus contributing to our understanding of the environmental impacts of nanomaterials and highlighting the need for further research and development of potential mitigation strategies.

Underlying anti-hypertensive mechanism of the Mizuhopecten yessoensis derived peptide NCW in spontaneously hypertensive rats via widely targeted kidney metabolomics

The angiotensin-converting enzyme(ACE)inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects,however,its anti-hypertensive mechanism is still not fully clarified.This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the antihypertensive mechanism of peptide NCW in spontaneously hypertensive rats(SHRs).Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHRUntreated groups.A total of 85 metabolites were differentially regulated,and 16 metabolites were identified as potential kidney biomarkers,e.g.,3-hydroxybutyrate,malonic acid,deoxycytidine,and L-aspartic acid.The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism,folate related pathways,synthesis and degradation of ketone bodies,pyrimidine metabolism,β-alanine metabolism,and retinal metabolism.

Integrated gut microbiota,plasma metabolomics and network pharmacology to reveal the anti-ischemic stroke effect of cooked rhubarb

Background:Cooked rhubarb(CR)is obtained by steaming raw rhubarb(Rheum palmatum L.,Rheum officinale Baill.,or Rheum tanguticum Maxim.ex Balf.)with millet wine.It is used as a traditional Chinese medicine for treating cerebral stroke,where patients often face severe constipation.This study explored the pharmacological effects and mechanisms of CR against ischemic stroke(IS)in rats.We used integrated analysis of gut microbiota,metabolomics,and network pharmacology.Methods:The compounds in CR were identified using LC-MS/MS.The impact of CR on rat middle cerebral artery occlusion/reperfusion(MCAO/R)-induced cerebral infarct size and brain tissue pathology was assessed through 2,3,5-triphenyl tetrazolium chloride and HE staining.Changes in hemorheology were measured by evaluating blood viscosity,and serum levels of pro-inflammatory cytokine were also determined.Gut microbiota composition was analyzed through 16S rRNA gene sequencing.Serum metabolites were examined using untargeted metabolomics and Spearman correlation analysis.The pseudo-germ-free test was used to determine whether tumour necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)improvement in IS are dependent on gut microbiota.Results:In vivo studies showed CR enhances neurobehavioral function in MCAO/R rats and reduces cerebral infarction area.CR also ameliorates brain and intestinal barrier damage caused by stroke.It also decreased inflammation and oxidative stress in IS rats.Furthermore,CR promotes the growth of Akkermansia and Verrucomicrobia,aiding in intestinal barrier repair.Notably,CR primarily influences the primary bile acid biosynthesis pathway.The pseudo-germ-free experiment and network pharmacology confirmed TNF-αand IL-1βas potential targets.CR relies on gut microbiota for its anti-inflammatory effects to improve IS.Conclusion:Cooked rhubarb offers neuroprotective benefits by enhancing beneficial bacteria abundance and regulating bile acid metabolism.It emerges as a potential therapeutic agent for IS.

Identification of key genes regulating the synthesis of quercetin derivatives in Rosa roxburghii through integrated transcriptomics and metabolomics

Rosa roxburghii fruit is rich in flavonoids, but little is known about their biosynthetic pathways. In this study, we employed transcriptomics and metabolomics to study changes related to the flavonoids at five different stages of R. roxburghii fruit development. Flavonoids and the genes related to their biosynthesis were found to undergo significant changes in abundance across different developmental stages, and numerous quercetin derivatives were identified. We found three gene expression modules that were significantly associated with the abundances of the different flavonoids in R. roxburghii and identified three structural UDP-glycosyltransferase genes directly involved in the synthesis of quercetin derivatives within these modules. In addition, we found that RrBEH4, RrLBD1 and RrPIF8could significantly increase the expression of downstream quercetin derivative biosynthesis genes. Taken together,these results provide new insights into the metabolism of flavonoids and the accumulation of quercetin derivatives in R. roxburghii.

Washed microbiota transplantation for Crohn’s disease:A metagenomic,metatranscriptomic,and metabolomic-based study

BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical phenomena.However,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been reported.AIM To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to WMT.METHODS We conducted a prospective,open-label,single-center clinical study.Eleven CD patients underwent WMT.Their clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the procedure.RESULTS Seven of the 11 patients(63.6%)showed an optimal clinical response three months post-WMT.Gut microbiome diversity significantly increased after WMT,consistent with improved clinical symptoms.Comparison of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia coli.In addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the donors.However,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after WMT.CONCLUSION WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s microbiome.Multi-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

Analysis of metabolic characteristics of metabolic syndrome in elderly patients with gastric cancer by non-targeted metabolomics

BACKGROUND The relationship between metabolic syndrome(MetS)and gastric cancer(GC),which is a common metabolic disease,has attracted much attention.However,the specific metabolic characteristics of MetS in elderly patients with GC remain unclear.AIM To investigate the differentially abundant metabolites and metabolic pathways between preoperative frailty and MetS in elderly patients with GC based on nontargeted metabolomics techniques.METHODS In this study,125 patients with nonfrail nonmeal GC were selected as the control group,and 50 patients with GC in the frail group were selected as the frail group.Sixty-five patients with GC combined with MetS alone were included in the MetS group,and 50 patients with GC combined with MetS were included in the MetS group.Nontargeted metabolomics techniques were used to measure plasma metabolite levels by ultrahigh-performance liquid chromatography-mass spectrometry.Multivariate statistical analysis was performed by principal component analysis,orthogonal partial least squares,pattern recognition analysis,cluster analysis,and metabolic pathway annotation.RESULTS A total of 125 different metabolites,including amino acids,glycerophospholipids,sphingolipids,fatty acids,sugars,nucleosides and nucleotides,and acidic compounds,were identified via nontargeted metabolomics techniques.Compared with those in the control group,there were 41,32,and 52 different metabolites in the MetS group,the debilitated group,and the combined group,respectively.Lipid metabolites were significantly increased in the MetS group.In the weak group,amino acids and most glycerol phospholipid metabolites decreased significantly,and fatty acids and sphingosine increased significantly.The combined group was characterized by significantly increased levels of nucleotide metabolites and acidic compounds.The alanine,aspartic acid,and glutamate metabolic pathways were obviously enriched in the asthenic group,and the glycerol and phospholipid metabolic pathways were obviously enriched in the combined group.CONCLUSION Elderly GC patients with simple frailty,simple combined MetS,and frailty combined with MetS have different metabolic characteristics,among which amino acid and glycerophospholipid metabolite levels are significantly lower in frail elderly GC patients,and comprehensive supplementation of fat and protein should be considered.Many kinds of metabolites,such as amino acids,lipids,nucleotides,and acidic compounds,are abnormally abundant in patients with MetS combined with fthenia,which may be related to tumor-related metabolic disorders.