Gestational diabetes mellitus(GDM)is a disease of glucose intolerance that first occurs during pregnancy.Accumulating evidence underlined a link between gut microbiota dysbiosis and GDM,and microbial metabolites repre...Gestational diabetes mellitus(GDM)is a disease of glucose intolerance that first occurs during pregnancy.Accumulating evidence underlined a link between gut microbiota dysbiosis and GDM,and microbial metabolites represent a unique way to explore microbiota-host interactions.However,the associations between changes in the gut microbiota and microbial metabolites and immune homeostasis in the GDM pathogenesis remain largely unclear.In this prospective study,the characteristics of gut microbiota in both first trimester(T1)and second trimester(T2)were investigated in 46 GDM patients and 44 matched controls.We comprehensively profiled the microbial metabolites using non-targeted metabolomics and quantitatively targeted metabolomics,measurements of inflammatory cytokines and biomarkers of intestinal barrier function,and combined with correlation analysis in T2.Gut microbiota dybiosis was observed in GDM patients in both T1 and T2,and was characterised by the enrichment of multiple potentially harmful bacteria,such as UBA1819 and Erysipelatoclostridium.Besides,alterations in the microbiota were accompanied by a disturbance in tryptophan metabolism,mainly manifested as a shift towards the production of more kynurenine and less indole derivatives.Most importantly,correlation network analysis indicated that overgrowth of potential pathogens and tryptophan metabolism disorder were associated with inflammatory imbalance and disrupted epithelial barrier in GDM patients.These findings provide a greater understanding of the pathogenesis and new targets for microecological interventions by mediating tryptophan metabolism in GDM.展开更多
Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal varia...Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.展开更多
In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Give...In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogramparameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome overan average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomicsapproach utilizing the Biocrates AbsoluteIDQ p180 kit. Next to intraclass correlation coefficients (ICC), which represent a measureof reliability, coefficients of variation within individuals(CVW) and coefficients of variation between individuals (CVB) were calculatedfor each metabolite to demonstrate its stability. Furthermore, men were divided into two cohorts, a similar sperm concentration(SSC) and a differing sperm concentration (DSC) cohort, based on the observed variance in sperm concentration between the twosemen donations. The ICC was higher in the SSC compared to the DSC cohort. The levels of 18 metabolites, primarily acylcarnitines,varied between the initial and subsequent donations. After subdivision into subgroups, only ornithine and phosphatidylcholine 40:5exhibited differential levels between the two donations in the SSC group, compared to 14 metabolites in the DSCgroup.CVBwashigher than CVW but both differed between the metabolite subclasses. Biogenic amines were identified as the least reliable analytesover time, exhibiting the highest CVW,compared to sphingomyelins, which demonstrated the highest reliability with the lowestvariation.CVB was the highest for ether-bound glycerophosphatidylcholines and the lowest for amino acids.展开更多
Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this e...Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide(GPSGRP)derived from sea cucumber in fructose induced hyperuricemia mouse model,and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites.Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice.In addition,treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level,Muribaculum,Prevotella and Bacteroides at the genus level,and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism.Moreover,serum metabolites,including linoleic acid,indole and its derivatives,arachidonic acid and uridine,as well as related metabolic pathways,such as tricarboxylic acid cycle,ketone production and sugar production,were altered in response to GPSGRP treatment.This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.展开更多
Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present ch...Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present challenges in sports settings.The study investigated sex-specific metabolic responses,addressing a significant gap in exercise research,where female participation remains underrepresented.Methods:To address this,we explored volumetrically accurate microsampling as a dried blood spot(DBS)technique for assessing metabolomic changes in response to acute exercise in more than 130 participants.This study employed a targeted quantitative approach using isotopically labeled internal standards to measure over 100 metabolites with DBS,providing accurate and traceable results.An accuracy assessment using standard reference material and stability testing over 90 days further evaluated the suitability of DBS for sports metabolomics.Results:Our findings confirm that DBS offers a valid approach to capture metabolic changes during exercise,with 11 compounds within the confidence interval of the reference material and 59 compounds overlapping with database values.A wide panel of metabolites showed significant changes in differences of absolute concentrations upon bout exercise,with succinate and xanthine being the most significant compounds.Metabolites from the underexplored class of pyrimidines also showed significant changes.Conclusion:While metabolic regulations upon exercise are similar in both sexes,differences in the correlation with fitness-related metadata,such as peak volitional oxygen consumption and performance,indicate a higher complexity in women and a limitation of previous knowledge to men only.The quantification approach together with the simplicity of the sampling paves the way to expand this type of research toward other fields of personalized medical services.展开更多
BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both s...BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.AIM To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites,distinct bacteria,and serum indicators.METHODS To uncover potentially effective therapeutic targets for HCC,we utilized nontargeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene.This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC.Furthermore,we conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.RESULTS In comparison to healthy controls,a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12(comprising patients with stage I and II HCC)and HCC34 groups(comprising patients with stage III and IV HCC).Lachnospira,Streptococcus,and Veillonella had significant differences in abundance in patients with HCC.Notably,Streptococcus and Veillonella exhibited significant correlations with serum indicators such as alpha-fetoprotein(AFP).Meanwhile,several differential metabolites[e.g.,4-keto-2-undecylpyrroline,dihydrojasmonic acid,1,8-heptadecadiene-4,6-diyne-3,10-diol,9(S)-HOTrE]also exhibited significant correlations with serum indicators such asγ-glutamyl transferase,total bilirubin,AFP,aspartate aminotransferase,and albumin.Additionally,these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol(15:0/20:0/0:0),arachidoyl ethanolamide,and 4-keto-2-undecylpyrroline.CONCLUSION Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.展开更多
AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equ...AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P < 0.001 and P < 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P < 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P < 0.05,and P < 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.展开更多
Background Dietary bamboo leaf flavonoids(BLFs)are rarely used in poultry production,and it is unknown whether they influence meat texture profile,perceived color,or microstructure.Results A total of 720 one-day-old A...Background Dietary bamboo leaf flavonoids(BLFs)are rarely used in poultry production,and it is unknown whether they influence meat texture profile,perceived color,or microstructure.Results A total of 720 one-day-old Arbor Acres broilers were supplemented with a basal diet with 20 mg bacitracin/kg,50 mg BLFs/kg,or 250 mg BLFs/kg or without additions.Data showed that the dietary BLFs significantly(P<0.05)changed growth performance and the texture profile.In particular,BLFs increased birds’average daily gain and average daily feed intake,decreased the feed:gain ratio and mortality rate,improved elasticity of breast meat,enhanced the gumminess of breast and leg meat,and decreased the hardness of breast meat.Moreover,a significant(P<0.05)increase in redness(a*)and chroma(c*)of breast meat and c*and water-holding capacity of leg meat was found in BLF-supplemented broilers compared with control broilers.In addition,BLFs supplementation significantly decreased(P<0.05)theβ-sheet ratio and serum malondialdehyde and increased theβ-turn ratio of protein secondary structure,superoxide dismutase,and glutathione peroxidase of breast meat and total antioxidant capacity and catalase of serum.Based on the analysis of untargeted metabolome,BLFs treatment considerably altered 14 metabolites of the breast meat,including flavonoids,amino acids,and organic acids,as well as phenolic and aromatic compounds.Conclusions Dietary BLFs supplementation could play a beneficial role in improving meat quality and sensory color in the poultry industry by changing protein secondary structures and modulating metabolites.展开更多
Freezing injury in winter is an important abiotic stress that seriously affects plant growth and development.Deciduous fruit trees resist freezing injury by inducing dormancy.However,different cultivars of the same sp...Freezing injury in winter is an important abiotic stress that seriously affects plant growth and development.Deciduous fruit trees resist freezing injury by inducing dormancy.However,different cultivars of the same species have different cold resistance strategies.Little is known about the molecular mechanism of apple trees in response to freezing injury during winter dormancy.Therefore,in this study,1-year-old branches of the cold-resistant cultivar‘Hanfu’(HF)and the cold-sensitive cultivar‘Changfuji No.2’(CF)were used to explore their cold resistance through physiological,biochemical,transcriptomics,and metabolomics analyses.Combining physiological and biochemical data,we found that HF had a stronger osmotic regulation ability and antioxidant enzyme activity than CF,as well as stronger cold resistance.The functional enrichment analysis showed that both cultivars were significantly enriched in pathways related to signal transduction,hormone regulation,and sugar metabolism under freezing stress.In addition,the differentially expressed genes(DEGs)encoding galactinol synthase,raffinose synthase,and stachyose synthetase in raffinose family oligosaccharides(RFOs)metabolic pathways were upregulated in HF,and raffinose and stachyose were accumulated,while their contents in CF were lower.HF accumulated 4-aminobutyric acid,spermidine,and ascorbic acid to scavenge reactive oxygen species(ROS).While the contents of oxidized glutathione,vitamin C,glutathione,and spermidine in CF decreased under freezing stress,consequently,the ability to scavenge ROS was low.Furthermore,the transcription factors apetala 2/ethylene responsive factor(AP2/ERF)and WRKY were strongly induced under freezing stress.In summary,the difference in key metabolic components of HF and CF under freezing stress is the major factor affecting their difference in cold resistance.The obtained results deepen our understanding of the cold resistance mechanism in apple trees in response to freezing injury during dormancy.展开更多
Schisandra chinensis Turcz.(Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of ph...Schisandra chinensis Turcz.(Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of physical exhaustion and to inhibit fatigue.The major bioactive compounds found in S. chinensis are lignans with a dibenzocyclooctadiene skeleton, but little is known about their biosynthesis in plants. S. chinensis is the ideal medicinal plant for studying the biosynthesis of lignans, especially the dibenzocyclooctadiene skeleton. Genomic information for this important herbal plant is unavailable. To better understand the lignan biosynthesis pathway, we generated transcriptome sequences from the fruit during ripening and performed de novo sequence assembly, yielding136 843 unique transcripts with N50 of 1778 bp. Putative functions could be assigned to 41 824 transcripts(51.57%) based on BLAST searches against annotation databases including GO(Gene ontology) and KEGG(Kyoto Encyclopedia of Genes and Genomes). Furthermore, 22 candidate cytochrome P450 genes and 15 candidate dirigent proteins genes that were most likely involved in the lignan biosynthesis pathway were discovered based on transcriptome sequencing of S. chinensis. The genomic data obtained from S. chinensis, especially the identification of putative genes involved in the lignan biosynthesis pathway, will facilitate our understanding of lignan biosynthesis at the molecular level. The lignan metabolite profiles were analyzed by metabolomes, the accumulation patterns of 30 metabolites involved in the lignan pathway were studied. Co-expression network of lignan contents and transcriptional changes showed355 strong correlations(correlation coefficient, R^2 > 0.9) between 21 compounds and 153 transcripts. Furthermore, the comprehensive analysis and characterization of the genes involved in lignan pathways and the metabolite profiles of lignans are expected to provide better insight regarding the diversity of the chemical composition, synthetic characteristics, and regulatory mechanisms of this medical herb.展开更多
Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic rela...Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mecha-nistic link between gastrointestinal dyshomeostasis and alcoholic liver injury.展开更多
BACKGROUND Intrahepatic cholestasis in pregnancy(ICP)is the most common liver disease during pregnancy,and its exact etiology and course of progression are still poorly understood.AIM To investigate the link between t...BACKGROUND Intrahepatic cholestasis in pregnancy(ICP)is the most common liver disease during pregnancy,and its exact etiology and course of progression are still poorly understood.AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients.METHODS In this study,a total of 30 patients were recruited,including 15 patients with ICP(disease group)and 15 healthy pregnant patients(healthy group).The serum nontarget metabolomes from both groups were determined.Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups.By comparing the differences in the microbiota and metabolite compositions between the two groups,the relationship between the gut microbiota and serum metabolites was also investigated.RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis,bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls.In addition,some pathways related to protein metabolism were also enriched in the ICP patients.The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition(beta diversity)between the ICP patients and healthy controls.At the phylum level,we observed that the relative abundance of Firmicutes was higher in the healthy group,while Bacteroidetes were enriched in the disease group.At the genus level,most of the bacteria depleted in ICP are able to produce short-chain fatty acids(e.g.,Faecalibacterium,Blautia and Eubacterium hallii),while the bacteria enriched in ICP are associated with bile acid metabolism(e.g.,Parabacteroides and Bilophila).Our results also showed that specific genera were associated with the serum metabolome.CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls,with significant differences in the bile,taurine and hypotaurine metabolite pathways.Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota,which may further affect the course of progression of ICP.展开更多
Background Providing high-quality roughage is crucial for improvement of ruminant production because it is an essential component of their feed.Our previous study showed that feeding bio-fermented rice straw(BF)improv...Background Providing high-quality roughage is crucial for improvement of ruminant production because it is an essential component of their feed.Our previous study showed that feeding bio-fermented rice straw(BF)improved the feed intake and weight gain of sheep.However,it remains unclear why feeding BF to sheep increased their feed intake and weight gain.Therefore,the purposes of this research were to investigate how the rumen micro-biota and serum metabolome are dynamically changing after feeding BF,as well as how their changes influence the feed intake,digestibility,nutrient transport,meat quality and growth performances of sheep.Twelve growing Hu sheep were allocated into 3 groups:alfalfa hay fed group(AH:positive control),rice straw fed group(RS:negative control)and BF fed group(BF:treatment).Samples of rumen content,blood,rumen epithelium,muscle,feed offered and refusals were collected for the subsequent analysis.Results Feeding BF changed the microbial community and rumen fermentation,particularly increasing(P<0.05)relative abundance of Prevotella and propionate production,and decreasing(P<0.05)enteric methane yield.The histomorphology(height,width,area and thickness)of rumen papillae and gene expression for carbohydrate trans-port(MCT1),tight junction(claudin-1,claudin-4),and cell proliferation(CDK4,Cyclin A2,Cyclin E1)were improved(P<0.05)in sheep fed BF.Additionally,serum metabolome was also dynamically changed,which led to up-regulating(P<0.05)the primary bile acid biosynthesis and biosynthesis of unsaturated fatty acid in sheep fed BF.As a result,the higher(P<0.05)feed intake,digestibility,growth rate,feed efficiency,meat quality and mono-unsaturated fatty acid concentration in muscle,and the lower(P<0.05)feed cost per kg of live weight were achieved by feeding BF.Conclusions Feeding BF improved the growth performances and meat quality of sheep and reduced their feed cost.Therefore,bio-fermentation of rice straw could be an innovative way for improving ruminant production with mini-mizing production costs.展开更多
Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, lead...Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.展开更多
Tomato spotted wilt virus(TSWV)is an important virus that has rapidly spread throughout the world.TSWV seriously hinders the production of tomato(Solanum lycopersicum)and other plants.In order to discover more new gen...Tomato spotted wilt virus(TSWV)is an important virus that has rapidly spread throughout the world.TSWV seriously hinders the production of tomato(Solanum lycopersicum)and other plants.In order to discover more new genes and metabolites related to TSWV resistance in tomato plants,the genes and metabolites related to the resistance of tomato plants inoculated with TSWV were identified and studied herein.The tomato TSWV-resistance line YNAU335(335)and TSWV-susceptible lines NO5 and 96172I(961)were used as the transcriptome and metabolome research materials.Transcriptomic and metabolomic techniques were used to analyze the gene and metabolite response mechanisms to TSWV inoculation.A total of 3566,2951,and 2674 differentially expressed genes(DEGs)were identified in lines 335,NO5,and961,respectively.Meanwhile,208,228,and 273 differentially accumulated metabolites(DAMs)were identified in lines 335,NO5,and 961,respectively.In line 335,the number of DEGs was the highest,but the number of DAMs was lowest.Furthermore,903 DEGs and 94 DAMs were common to the response to TSWV in the three inbred lines.The 903 DEGs and 94 DAMs were mainly enriched in the plant hormone signal transduction and flavonoid synthesis pathways.In addition,many nucleotide-binding site-leucine-rich repeat genes and transcription factors were found that might be involved in the TSWV response.These results provide new insights into TSWV resistance mechanisms.展开更多
We conducted an integrative system biology of metabolome and transcriptome profile analyses during pomegranate(Punica granatum L.) seed germination and utilized a weighted gene co-expression network analysis(WGCNA) to...We conducted an integrative system biology of metabolome and transcriptome profile analyses during pomegranate(Punica granatum L.) seed germination and utilized a weighted gene co-expression network analysis(WGCNA) to describe the functionality and complexity of the physiological and morphogenetic processes as well as gene expression and metabolic differences during seed germination stages. In total, 489 metabolites were detected, including 40 differentially accumulated metabolites. The transcriptomic analysis showed the expression of 6 984 genes changed significantly throughout the whole germination process. Using WGCNA, we identified modules related to the various seed germination stages and hub genes. In the initial imbibition stage(stage 1), the pivotal genes involved in RNA transduction and the glycolytic pathway were most active, while in the sprouting stage(stage 4), the pivotal genes were involved in multiple metabolic pathways. In terms of secondary metabolic pathways, we found flavonoid 4-reductase genes of anthocyanin biosynthesis pathway are most significantly affected during pomegranate seed germination, while the flavonol synthase gene was mainly involved in the regulation of isoflavonoid biosynthesis.展开更多
Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many years.However,the mechanisms of multilevel regulation of cell fate determination r...Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many years.However,the mechanisms of multilevel regulation of cell fate determination remain unclear.Recently,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell reprogramming.In this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic processes.Precise E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.展开更多
BACKGROUND Helicobacter pylori(H.pylori),a bacterium that infects approximately half of the world’s population,is associated with various gastrointestinal diseases,including peptic ulcers,non-ulcer dyspepsia,gastric ...BACKGROUND Helicobacter pylori(H.pylori),a bacterium that infects approximately half of the world’s population,is associated with various gastrointestinal diseases,including peptic ulcers,non-ulcer dyspepsia,gastric adenocarcinoma,and gastric lymphoma.As the burden of antibiotic resistance increases,the need for new adjunct therapies designed to facilitate H.pylori eradication and reduce negative distal outcomes associated with infection has become more pressing.Characterization of the interactions between H.pylori,the fecal microbiome,and fecal fatty acid metabolism,as well as the mechanisms underlying these interactions,may offer new therapeutic approaches.AIM To characterize the gut microbiome and metabolome in H.pylori patients in a socioeconomically challenged and underprivileged inner-city community.METHODS Stool samples from 19 H.pylori patients and 16 control subjects were analyzed.16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2.Alpha and beta diversity analyses were performed in QIIME 2.Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry,which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters.Multi-dimensional scaling(MDS)was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates.RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in H.pylori patients over 40 years of age compared to control subjects of similar age group.Beta diversity analysis of the samples revealed significant differences in microbial community structure between H.pylori patients and control subjects across all ages.Thirty-eight and six taxa had lower and higher relative abundance in H.pylori patients,respectively.Taxa that were enriched in H.pylori patients included Atopobium,Gemellaceae,Micrococcaceae,Gemellales and Rothia(R.mucilaginosa).Notably,relative abundance of the phylum Verrucomicrobia was decreased in H.pylori patients compared to control subjects.Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets.Stool samples from H.pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids(PUFAs)22:4n6,22:5n3,20:3n6 and 22:2n6,while decreases were noted in other fatty acids including the PUFA 18:3n6.The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis.CONCLUSION This exploratory study demonstrates H.pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism.Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.展开更多
Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying protein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in r...Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying protein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in response to these molecular malfunctions and treatment is often too late or restricted only to the slowing of further cell death. Important new strategies to identify early biomarkers with predictive value to intervene with disease progression at stages where cell dysfunction has not progressed irreversibly is of paramount importance. Thus, the identification of these markers presents an essential opportunity to identify and target disease pathways. This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways identified across different neurodegenerative diseases. Thus, having established some commonalities between various degenerative conditions, detectable metabolic changes may be of extreme value as an early diagnostic biomarker in disease.展开更多
Globally, the third cause of males cancer and the fourth cause of females cancer is colon cancer(CC). In Egypt, high CC percentage occurs in children and in individuals below 40 years of age. The complete loss of biol...Globally, the third cause of males cancer and the fourth cause of females cancer is colon cancer(CC). In Egypt, high CC percentage occurs in children and in individuals below 40 years of age. The complete loss of biological enzyme function is the main cause of CC and consequently CC increased in smoking and pollution exposure. The aim of this review is to focus on the application of metabolome as a physiological tool that can play an important role in preventing CC incidence by natural products and hormones. The dietary factors, intestinal micro-flora and endogenously produced metabolites are the main three causes that produce free radicals in the colon. A correlation occurs between the enzyme activity and CC polymorphisms or property. Nowadays metabolome is applied with the progress of different analytical methods, data bases and tools for cancer predication and stimulation especially in CC cases. Metabolism is defined as intracellular chemical reactions that produce chemical substances and energies sustaining life. Metabolic pathway networks are also composed of links that are defined as transformation of chemical structures between two metabolites and an enzyme reaction. The most important advantage of metabolome is its ability to analyze metabolites from any source, regardless of origin, where the application of liquid chromatography combined with mass spectra in metabolome analysis to a series of cancer cell lines that were progressively more tumorigenic due to the induction of 1,2,3 or 4 oncogenes to cell lines could be a metabolome example application. In conclusion, natural products and hormones are very important in preventing CC in humans and animal models where both natural products and hormones play a significant and important effect in regulating physiological process especially in CC cases. In this situation, metabolome must increase in its application in the future for the diagnosis of CC cases.展开更多
基金supported by the National Natural Science Foundation of China(32272332,32021005)the Fundamental Research Funds for the Central Universities(JUSRP622020,JUSRP22006,and JUSRP51501)+2 种基金the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu ProvinceTop Talent Support Program for Young and Middle-aged People of Wuxi Health Committee(bj2020111)Appropriate Technology Promotion Project of Wuxi Municipal Health Commission(FYTG202006)。
文摘Gestational diabetes mellitus(GDM)is a disease of glucose intolerance that first occurs during pregnancy.Accumulating evidence underlined a link between gut microbiota dysbiosis and GDM,and microbial metabolites represent a unique way to explore microbiota-host interactions.However,the associations between changes in the gut microbiota and microbial metabolites and immune homeostasis in the GDM pathogenesis remain largely unclear.In this prospective study,the characteristics of gut microbiota in both first trimester(T1)and second trimester(T2)were investigated in 46 GDM patients and 44 matched controls.We comprehensively profiled the microbial metabolites using non-targeted metabolomics and quantitatively targeted metabolomics,measurements of inflammatory cytokines and biomarkers of intestinal barrier function,and combined with correlation analysis in T2.Gut microbiota dybiosis was observed in GDM patients in both T1 and T2,and was characterised by the enrichment of multiple potentially harmful bacteria,such as UBA1819 and Erysipelatoclostridium.Besides,alterations in the microbiota were accompanied by a disturbance in tryptophan metabolism,mainly manifested as a shift towards the production of more kynurenine and less indole derivatives.Most importantly,correlation network analysis indicated that overgrowth of potential pathogens and tryptophan metabolism disorder were associated with inflammatory imbalance and disrupted epithelial barrier in GDM patients.These findings provide a greater understanding of the pathogenesis and new targets for microecological interventions by mediating tryptophan metabolism in GDM.
基金supported by grants from Singhealth Duke-NUS Academic Medicine Research grant(AM/SU035/2020)NMRC Clinician-Scientist Individual Research Grant New Investigator Grant(CNIG20nov-0003).
文摘Chemical exposure during prenatal development has significant implications for both maternal and child health.Compared to blood,saliva is a non-invasive and less resource-intensive,alternative.Given the temporal variability of xenobiotic metabolites(XM),repeated sampling is essential.Therefore,saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes.Despite its potential,no studies have explored saliva for XM measurement.This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women.Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24–34 weeks gestation.Metabolomes and exposomes were annotated using the Human Metabolome and U.S.Environmental Protection Agency databases.Metabolome-XM associations were clustered using Glay community clustering.Linear regression models,adjusted for age,estimated associations between catecholamines and XMs.XM levels were validated in a cohort of women(n=14)with and without preeclampsia.Our study identified 582 metabolomes and 125 XM in saliva,demonstrating its potential as a matrix for exposure measurement.After false discovery rate correction,18109 significant metabolome-XM associations were identified.Community clustering revealed 37 connected clusters,with the largest cluster(238 nodes)enriched in tyrosine and catecholamine metabolism.Food-contactchemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels.Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls.This study demonstrates that saliva contains valuable molecular data for measuring exposomes.Food-related chemicals were associated with higher catecholamine levels,which may be relevant to the prevalence of hypertensive crises in pregnancy.
文摘In contrast to the conventional spermiogram, metabolomics approaches give insights into the molecular composition of semen and mayprovide more detailed information on the fertility status of the respective donor. Given the intra-individual variability of spermiogramparameters between two donations, this study sought to elucidate the biological variability of the seminal plasma metabolome overan average period of 8 weeks. Two time-shifted semen samples from 15 healthy donors were compared by a targeted metabolomicsapproach utilizing the Biocrates AbsoluteIDQ p180 kit. Next to intraclass correlation coefficients (ICC), which represent a measureof reliability, coefficients of variation within individuals(CVW) and coefficients of variation between individuals (CVB) were calculatedfor each metabolite to demonstrate its stability. Furthermore, men were divided into two cohorts, a similar sperm concentration(SSC) and a differing sperm concentration (DSC) cohort, based on the observed variance in sperm concentration between the twosemen donations. The ICC was higher in the SSC compared to the DSC cohort. The levels of 18 metabolites, primarily acylcarnitines,varied between the initial and subsequent donations. After subdivision into subgroups, only ornithine and phosphatidylcholine 40:5exhibited differential levels between the two donations in the SSC group, compared to 14 metabolites in the DSCgroup.CVBwashigher than CVW but both differed between the metabolite subclasses. Biogenic amines were identified as the least reliable analytesover time, exhibiting the highest CVW,compared to sphingomyelins, which demonstrated the highest reliability with the lowestvariation.CVB was the highest for ether-bound glycerophosphatidylcholines and the lowest for amino acids.
基金sponsored by the One Health Interdisciplinary Research Project,Ningbo University,Open Fund of Key Laboratory of Aquacultural Biotechnology Ministry of Education in Ningbo University,and K.C.Wong Magna Fund of Ningbo Universitythe National Natural Science Foundation China(32270115)+1 种基金National Key R&D Program of China(2018YFD0901102)Fundamental Research Funds for the Provincial Universities of Zhejiang(SJLY2021015)。
文摘Fructose consumption has risen dramatically in recent decades due to the use of sucrose and high fructose corn syrup in beverages and processed foods,contributing to rising rates of hyperuricemia.The purpose of this experiment was to explore the anti-hyperuricemia effects of an active oligopeptide(GPSGRP)derived from sea cucumber in fructose induced hyperuricemia mouse model,and to clarify the underlying mechanism in sight of gut microbiota and serum metabolites.Peptide GPSGRP treatment rebalanced uric acid metabolism and alleviated inflammatory response in mice.In addition,treatment with GPSGRP decreased the abundance of Bacteroides and Proteobacteria at the phylum level,Muribaculum,Prevotella and Bacteroides at the genus level,and inhibited the related pathways of purine metabolism and glycolysis/gluconeogenesis metabolism.Moreover,serum metabolites,including linoleic acid,indole and its derivatives,arachidonic acid and uridine,as well as related metabolic pathways,such as tricarboxylic acid cycle,ketone production and sugar production,were altered in response to GPSGRP treatment.This study provides a valuable reference for the application and development of marine biological peptides in uric acid management.
基金This work is supported by the University of Vienna,the Faculty of Chemistry and Centre for Sport Science and University Sports.The Vienna Business Agency,Austria funded FR.
文摘Background:Integrating metabolomics in sports science provides valuable insights into the biochemistry of bodies during physical activity.However,due to their invasiveness,traditional blood sampling methods present challenges in sports settings.The study investigated sex-specific metabolic responses,addressing a significant gap in exercise research,where female participation remains underrepresented.Methods:To address this,we explored volumetrically accurate microsampling as a dried blood spot(DBS)technique for assessing metabolomic changes in response to acute exercise in more than 130 participants.This study employed a targeted quantitative approach using isotopically labeled internal standards to measure over 100 metabolites with DBS,providing accurate and traceable results.An accuracy assessment using standard reference material and stability testing over 90 days further evaluated the suitability of DBS for sports metabolomics.Results:Our findings confirm that DBS offers a valid approach to capture metabolic changes during exercise,with 11 compounds within the confidence interval of the reference material and 59 compounds overlapping with database values.A wide panel of metabolites showed significant changes in differences of absolute concentrations upon bout exercise,with succinate and xanthine being the most significant compounds.Metabolites from the underexplored class of pyrimidines also showed significant changes.Conclusion:While metabolic regulations upon exercise are similar in both sexes,differences in the correlation with fitness-related metadata,such as peak volitional oxygen consumption and performance,indicate a higher complexity in women and a limitation of previous knowledge to men only.The quantification approach together with the simplicity of the sampling paves the way to expand this type of research toward other fields of personalized medical services.
基金Supported by the Department of Science and Technology of Shanxi Province,No.20210302124369the Health Commission of Shanxi Province,No.2021116Shanxi Administration of Traditional Chinese Medicine,No.2024ZYY2C054.
文摘BACKGROUND Hepatocellular carcinoma(HCC),the predominant form of primary liver cancer,is a key contributor to cancer-related deaths globally.However,HCC diagnosis solely based on blood biochemical markers lacks both sensitivity and specificity.AIM To investigate alterations of the fecal metabolome and intestinal bacteria and reveal the correlations among differential metabolites,distinct bacteria,and serum indicators.METHODS To uncover potentially effective therapeutic targets for HCC,we utilized nontargeted liquid chromatography-mass spectrometry and high-throughput DNA sequencing targeting the 16S rRNA gene.This comprehensive approach allowed us to investigate the metabolome and microbial community structure of feces samples obtained from patients with HCC.Furthermore,we conducted an analysis to assess the interplay between the fecal metabolome and intestinal bacterial population.RESULTS In comparison to healthy controls,a notable overlap of 161 differential metabolites and 3 enriched Kyoto Encyclopedia of Genes and Genomes pathways was observed in the HCC12(comprising patients with stage I and II HCC)and HCC34 groups(comprising patients with stage III and IV HCC).Lachnospira,Streptococcus,and Veillonella had significant differences in abundance in patients with HCC.Notably,Streptococcus and Veillonella exhibited significant correlations with serum indicators such as alpha-fetoprotein(AFP).Meanwhile,several differential metabolites[e.g.,4-keto-2-undecylpyrroline,dihydrojasmonic acid,1,8-heptadecadiene-4,6-diyne-3,10-diol,9(S)-HOTrE]also exhibited significant correlations with serum indicators such asγ-glutamyl transferase,total bilirubin,AFP,aspartate aminotransferase,and albumin.Additionally,these two genera also had significant associations with differential metabolites such as 1,2-Dipentadecanoyl-rac-glycerol(15:0/20:0/0:0),arachidoyl ethanolamide,and 4-keto-2-undecylpyrroline.CONCLUSION Our results suggest that the metabolome of fecal samples and the composition of intestinal bacteria hold promise as potential biomarkers for HCC diagnosis.
基金the National Natural Science Foundation of China,No.81330011,No.81790631,and No.81790633the Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No.81721091the National Basic Research Program of China(973 program),No.2013CB531401
文摘AIM To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis(NASH) development in mice fed a methionine-choline-deficient(MCD) diet. METHODS Twenty-four male C57 BL/6 J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk(Control 2 w group,n = 6) or 4 wk(Control 4 w group,n = 6) or the MCD diet for 2 wk(MCD 2 w group,n = 6) or 4 wk(MCD 4 w group,n = 6). Liver injury,fibrosis,and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16 s r RNA deep sequencing and gas chromatography-mass spectrometry. RESULTS The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet,however,the mice developed prominent NASH with liver fibrosis,and the intestinal barrier was more impaired. Compared with the control diet,the MCD diet induced gradual gut microbiota dysbiosis,as evidenced by a marked decrease in the abundance of Alistipes and the(Eubacterium) coprostanoligenes group(P < 0.001 and P < 0.05,respectively) and a significant increase in Ruminococcaceae UCG 014 abundance(P < 0.05) after 2 wk. At 4 wk,the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance(P < 0.05,and P < 0.01,respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk,arachidic acid,hexadecane,palmitic acid,and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group,and at 4 wk,cholic acid,cholesterol,arachidic acid,tetracosane,and stearic acid were selected. CONCLUSION The MCD diet induced persistent alterations in the gut microbiota and metabolome.
基金supported by the National Natural Science Foundation of China(No.32002195)Zhejiang Provincial Leading Innovation and Entrepreneurship Team Project(No.2020R01015)+1 种基金“Leading Geese”Research and Development Plan of Zhejiang Province(No.2022C02059)Key R&D Projects of Zhejiang Province(No.2021C02013)。
文摘Background Dietary bamboo leaf flavonoids(BLFs)are rarely used in poultry production,and it is unknown whether they influence meat texture profile,perceived color,or microstructure.Results A total of 720 one-day-old Arbor Acres broilers were supplemented with a basal diet with 20 mg bacitracin/kg,50 mg BLFs/kg,or 250 mg BLFs/kg or without additions.Data showed that the dietary BLFs significantly(P<0.05)changed growth performance and the texture profile.In particular,BLFs increased birds’average daily gain and average daily feed intake,decreased the feed:gain ratio and mortality rate,improved elasticity of breast meat,enhanced the gumminess of breast and leg meat,and decreased the hardness of breast meat.Moreover,a significant(P<0.05)increase in redness(a*)and chroma(c*)of breast meat and c*and water-holding capacity of leg meat was found in BLF-supplemented broilers compared with control broilers.In addition,BLFs supplementation significantly decreased(P<0.05)theβ-sheet ratio and serum malondialdehyde and increased theβ-turn ratio of protein secondary structure,superoxide dismutase,and glutathione peroxidase of breast meat and total antioxidant capacity and catalase of serum.Based on the analysis of untargeted metabolome,BLFs treatment considerably altered 14 metabolites of the breast meat,including flavonoids,amino acids,and organic acids,as well as phenolic and aromatic compounds.Conclusions Dietary BLFs supplementation could play a beneficial role in improving meat quality and sensory color in the poultry industry by changing protein secondary structures and modulating metabolites.
基金funded by the National Key Research and Development Program of China(Grant No.2020YFD1000201)China Agriculture Research System of MOF and MARA(Grant No.CARS-27)+1 种基金the National Natural Science Foundation of China(Grant No.31972359)the Agricultural Research and Industrialization Project of Liaoning Province(Grant No.2020JH2/10200028).
文摘Freezing injury in winter is an important abiotic stress that seriously affects plant growth and development.Deciduous fruit trees resist freezing injury by inducing dormancy.However,different cultivars of the same species have different cold resistance strategies.Little is known about the molecular mechanism of apple trees in response to freezing injury during winter dormancy.Therefore,in this study,1-year-old branches of the cold-resistant cultivar‘Hanfu’(HF)and the cold-sensitive cultivar‘Changfuji No.2’(CF)were used to explore their cold resistance through physiological,biochemical,transcriptomics,and metabolomics analyses.Combining physiological and biochemical data,we found that HF had a stronger osmotic regulation ability and antioxidant enzyme activity than CF,as well as stronger cold resistance.The functional enrichment analysis showed that both cultivars were significantly enriched in pathways related to signal transduction,hormone regulation,and sugar metabolism under freezing stress.In addition,the differentially expressed genes(DEGs)encoding galactinol synthase,raffinose synthase,and stachyose synthetase in raffinose family oligosaccharides(RFOs)metabolic pathways were upregulated in HF,and raffinose and stachyose were accumulated,while their contents in CF were lower.HF accumulated 4-aminobutyric acid,spermidine,and ascorbic acid to scavenge reactive oxygen species(ROS).While the contents of oxidized glutathione,vitamin C,glutathione,and spermidine in CF decreased under freezing stress,consequently,the ability to scavenge ROS was low.Furthermore,the transcription factors apetala 2/ethylene responsive factor(AP2/ERF)and WRKY were strongly induced under freezing stress.In summary,the difference in key metabolic components of HF and CF under freezing stress is the major factor affecting their difference in cold resistance.The obtained results deepen our understanding of the cold resistance mechanism in apple trees in response to freezing injury during dormancy.
基金supported by the Achievement Conversion Project of the Ministry of Science and Technology (No.2014GB2B100007)the Science and Technology Project of Education Department of Jilin Province (No. JJKH20180640KJ)。
文摘Schisandra chinensis Turcz.(Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of physical exhaustion and to inhibit fatigue.The major bioactive compounds found in S. chinensis are lignans with a dibenzocyclooctadiene skeleton, but little is known about their biosynthesis in plants. S. chinensis is the ideal medicinal plant for studying the biosynthesis of lignans, especially the dibenzocyclooctadiene skeleton. Genomic information for this important herbal plant is unavailable. To better understand the lignan biosynthesis pathway, we generated transcriptome sequences from the fruit during ripening and performed de novo sequence assembly, yielding136 843 unique transcripts with N50 of 1778 bp. Putative functions could be assigned to 41 824 transcripts(51.57%) based on BLAST searches against annotation databases including GO(Gene ontology) and KEGG(Kyoto Encyclopedia of Genes and Genomes). Furthermore, 22 candidate cytochrome P450 genes and 15 candidate dirigent proteins genes that were most likely involved in the lignan biosynthesis pathway were discovered based on transcriptome sequencing of S. chinensis. The genomic data obtained from S. chinensis, especially the identification of putative genes involved in the lignan biosynthesis pathway, will facilitate our understanding of lignan biosynthesis at the molecular level. The lignan metabolite profiles were analyzed by metabolomes, the accumulation patterns of 30 metabolites involved in the lignan pathway were studied. Co-expression network of lignan contents and transcriptional changes showed355 strong correlations(correlation coefficient, R^2 > 0.9) between 21 compounds and 153 transcripts. Furthermore, the comprehensive analysis and characterization of the genes involved in lignan pathways and the metabolite profiles of lignans are expected to provide better insight regarding the diversity of the chemical composition, synthetic characteristics, and regulatory mechanisms of this medical herb.
文摘Alcohol consumption is one of the leading causes of liver diseases and liver-related death worldwide. The gut is a habitat for billions of microorganisms which promotes metabolism and digestion in their symbiotic relationship with the host. Alterations of gut microbiome by alcohol consumption are referred to bacterial overgrowth, release of bacteria-derived products, and/or changed microbiota equilibrium. Alcohol consumption also perturbs the function of gastrointestinal mucosa and elicits a pathophysiological condition. These adverse effects caused by alcohol may ultimately result in a broad change of gastrointestinal luminal metabolites such as bile acids, short chain fatty acids, and branched chain amino acids. Gut microbiota alterations, metabolic changes produced in a dysbiotic intestinal environment, and the host factors are all critical contributors to the development and progression of alcoholic liver disease. This review summarizes recent findings of how alcohol-induced alterations of gut microbiota and metabolome, and discusses the mecha-nistic link between gastrointestinal dyshomeostasis and alcoholic liver injury.
基金Supported by the Technology Project of Shanghai Pudong New District Health and Family Planning Commission,No.PW2019D-9.
文摘BACKGROUND Intrahepatic cholestasis in pregnancy(ICP)is the most common liver disease during pregnancy,and its exact etiology and course of progression are still poorly understood.AIM To investigate the link between the gut microbiota and serum metabolome in ICP patients.METHODS In this study,a total of 30 patients were recruited,including 15 patients with ICP(disease group)and 15 healthy pregnant patients(healthy group).The serum nontarget metabolomes from both groups were determined.Amplification of the 16S rRNA V3-V4 region was performed using fecal samples from the disease and healthy groups.By comparing the differences in the microbiota and metabolite compositions between the two groups,the relationship between the gut microbiota and serum metabolites was also investigated.RESULTS The Kyoto Encyclopedia of Genes and Genomes analysis results showed that the primary bile acid biosynthesis,bile secretion and taurine and hypotaurine metabolism pathways were enriched in the ICP patients compared with the healthy controls.In addition,some pathways related to protein metabolism were also enriched in the ICP patients.The principal coordination analysis results showed that there was a distinct difference in the gut microbiota composition(beta diversity)between the ICP patients and healthy controls.At the phylum level,we observed that the relative abundance of Firmicutes was higher in the healthy group,while Bacteroidetes were enriched in the disease group.At the genus level,most of the bacteria depleted in ICP are able to produce short-chain fatty acids(e.g.,Faecalibacterium,Blautia and Eubacterium hallii),while the bacteria enriched in ICP are associated with bile acid metabolism(e.g.,Parabacteroides and Bilophila).Our results also showed that specific genera were associated with the serum metabolome.CONCLUSION Our study showed that the serum metabolome was altered in ICP patients compared to healthy controls,with significant differences in the bile,taurine and hypotaurine metabolite pathways.Alterations in the metabolization of these pathways may lead to disturbances in the gut microbiota,which may further affect the course of progression of ICP.
基金This research was supported by the National Natural Science Foundation of China(32061143034,32161143028)Tibet Regional Science and Technology Collaborative Innovation Project(QYXTZX-NQ2021-01)Fundamental Research Funds for the Central Universities(lzujbky-2022-ct04).
文摘Background Providing high-quality roughage is crucial for improvement of ruminant production because it is an essential component of their feed.Our previous study showed that feeding bio-fermented rice straw(BF)improved the feed intake and weight gain of sheep.However,it remains unclear why feeding BF to sheep increased their feed intake and weight gain.Therefore,the purposes of this research were to investigate how the rumen micro-biota and serum metabolome are dynamically changing after feeding BF,as well as how their changes influence the feed intake,digestibility,nutrient transport,meat quality and growth performances of sheep.Twelve growing Hu sheep were allocated into 3 groups:alfalfa hay fed group(AH:positive control),rice straw fed group(RS:negative control)and BF fed group(BF:treatment).Samples of rumen content,blood,rumen epithelium,muscle,feed offered and refusals were collected for the subsequent analysis.Results Feeding BF changed the microbial community and rumen fermentation,particularly increasing(P<0.05)relative abundance of Prevotella and propionate production,and decreasing(P<0.05)enteric methane yield.The histomorphology(height,width,area and thickness)of rumen papillae and gene expression for carbohydrate trans-port(MCT1),tight junction(claudin-1,claudin-4),and cell proliferation(CDK4,Cyclin A2,Cyclin E1)were improved(P<0.05)in sheep fed BF.Additionally,serum metabolome was also dynamically changed,which led to up-regulating(P<0.05)the primary bile acid biosynthesis and biosynthesis of unsaturated fatty acid in sheep fed BF.As a result,the higher(P<0.05)feed intake,digestibility,growth rate,feed efficiency,meat quality and mono-unsaturated fatty acid concentration in muscle,and the lower(P<0.05)feed cost per kg of live weight were achieved by feeding BF.Conclusions Feeding BF improved the growth performances and meat quality of sheep and reduced their feed cost.Therefore,bio-fermentation of rice straw could be an innovative way for improving ruminant production with mini-mizing production costs.
基金supported by National Natural Science Foundation of China [No. 81773405 to Y.Q. and No. 82173644to X.Y.]Shanxi Natural Science Foundation of China [No.202203021211246 and No. 202103021224242]。
文摘Objective Arsenic(As) and fluoride(F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level(microbiome and metabolome).Methods We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.Results Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome, featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic(GABAergic) synapse, and arachidonic acid(AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.Conclusion Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
基金funded by the National Natural Science Foundation of China(Grant Nos.32160715,31660576,31760583)the Joint Project of Basic Agricultural Research in Yunnan Province(Grant No.2018FG001-004)+3 种基金Yunnan Luxi County Vegetable Industry Science and Technology Mission project(Grant No.202204BI090006)the General Project of Yunnan Science and Technology Plan(Grant No.2016FB064)High-level Scientific Research Foundation of Yunnan Agricultural University(Grant No.KY2022-27)Research and Integrated Applications of Key Technology in Standardized Production of Facility Vegetables(Grant No.202102AE090005)。
文摘Tomato spotted wilt virus(TSWV)is an important virus that has rapidly spread throughout the world.TSWV seriously hinders the production of tomato(Solanum lycopersicum)and other plants.In order to discover more new genes and metabolites related to TSWV resistance in tomato plants,the genes and metabolites related to the resistance of tomato plants inoculated with TSWV were identified and studied herein.The tomato TSWV-resistance line YNAU335(335)and TSWV-susceptible lines NO5 and 96172I(961)were used as the transcriptome and metabolome research materials.Transcriptomic and metabolomic techniques were used to analyze the gene and metabolite response mechanisms to TSWV inoculation.A total of 3566,2951,and 2674 differentially expressed genes(DEGs)were identified in lines 335,NO5,and961,respectively.Meanwhile,208,228,and 273 differentially accumulated metabolites(DAMs)were identified in lines 335,NO5,and 961,respectively.In line 335,the number of DEGs was the highest,but the number of DAMs was lowest.Furthermore,903 DEGs and 94 DAMs were common to the response to TSWV in the three inbred lines.The 903 DEGs and 94 DAMs were mainly enriched in the plant hormone signal transduction and flavonoid synthesis pathways.In addition,many nucleotide-binding site-leucine-rich repeat genes and transcription factors were found that might be involved in the TSWV response.These results provide new insights into TSWV resistance mechanisms.
基金supported by the Doctorate Fellowship Foundation of Nanjing Forestry University, China (163010550)the Priority Academic Program Development of Jiangsu High Education Institutions, China (PAPD)。
文摘We conducted an integrative system biology of metabolome and transcriptome profile analyses during pomegranate(Punica granatum L.) seed germination and utilized a weighted gene co-expression network analysis(WGCNA) to describe the functionality and complexity of the physiological and morphogenetic processes as well as gene expression and metabolic differences during seed germination stages. In total, 489 metabolites were detected, including 40 differentially accumulated metabolites. The transcriptomic analysis showed the expression of 6 984 genes changed significantly throughout the whole germination process. Using WGCNA, we identified modules related to the various seed germination stages and hub genes. In the initial imbibition stage(stage 1), the pivotal genes involved in RNA transduction and the glycolytic pathway were most active, while in the sprouting stage(stage 4), the pivotal genes were involved in multiple metabolic pathways. In terms of secondary metabolic pathways, we found flavonoid 4-reductase genes of anthocyanin biosynthesis pathway are most significantly affected during pomegranate seed germination, while the flavonol synthase gene was mainly involved in the regulation of isoflavonoid biosynthesis.
基金financially supported by the National Key Research and Development Program of China (2017YFA0106300)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16030505)+6 种基金the National Natural Science Foundation projects of China (2017YFA0102900, 2019YFA09004500, 2017YFC1001602, 2016YFA0100300, 2018YFA0107100)the National Natural Science Foundation projects of China (92157202, 32025010, 31801168, 31900614, 31970709, 81901275, 32070729, 32100619, 32170747)the Key Research Program of Frontier Sciences, CAS (QYZDB-SSW-SMC001)International Cooperation Program (154144KYSB20200006)Guangdong Province Science and Technology Program (2020B1212060052, 2018A030313825, 2018GZR110103002, 2020A1515011200, 2020A1515010919, 2020A1515011410, 2021A1515012513)Guangzhou Science and Technology Program (201807010067, 202002030277, 202102021250, 202102020827, 202102080066), Open Research Program of Key Laboratory of Regenerative Biology, CAS (KLRB201907, KLRB202014)CAS Youth Innovation Promotion Association (to Y. W. and K. C.)
文摘Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many years.However,the mechanisms of multilevel regulation of cell fate determination remain unclear.Recently,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell reprogramming.In this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic processes.Precise E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.
文摘BACKGROUND Helicobacter pylori(H.pylori),a bacterium that infects approximately half of the world’s population,is associated with various gastrointestinal diseases,including peptic ulcers,non-ulcer dyspepsia,gastric adenocarcinoma,and gastric lymphoma.As the burden of antibiotic resistance increases,the need for new adjunct therapies designed to facilitate H.pylori eradication and reduce negative distal outcomes associated with infection has become more pressing.Characterization of the interactions between H.pylori,the fecal microbiome,and fecal fatty acid metabolism,as well as the mechanisms underlying these interactions,may offer new therapeutic approaches.AIM To characterize the gut microbiome and metabolome in H.pylori patients in a socioeconomically challenged and underprivileged inner-city community.METHODS Stool samples from 19 H.pylori patients and 16 control subjects were analyzed.16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2.Alpha and beta diversity analyses were performed in QIIME 2.Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry,which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters.Multi-dimensional scaling(MDS)was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates.RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in H.pylori patients over 40 years of age compared to control subjects of similar age group.Beta diversity analysis of the samples revealed significant differences in microbial community structure between H.pylori patients and control subjects across all ages.Thirty-eight and six taxa had lower and higher relative abundance in H.pylori patients,respectively.Taxa that were enriched in H.pylori patients included Atopobium,Gemellaceae,Micrococcaceae,Gemellales and Rothia(R.mucilaginosa).Notably,relative abundance of the phylum Verrucomicrobia was decreased in H.pylori patients compared to control subjects.Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets.Stool samples from H.pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids(PUFAs)22:4n6,22:5n3,20:3n6 and 22:2n6,while decreases were noted in other fatty acids including the PUFA 18:3n6.The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis.CONCLUSION This exploratory study demonstrates H.pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism.Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.
文摘Neurodegenerative disorders are often associated with cellular dysfunction caused by underlying protein-misfolding signalling. Numerous neuropathologies are diagnosed at late stage symptomatic changes which occur in response to these molecular malfunctions and treatment is often too late or restricted only to the slowing of further cell death. Important new strategies to identify early biomarkers with predictive value to intervene with disease progression at stages where cell dysfunction has not progressed irreversibly is of paramount importance. Thus, the identification of these markers presents an essential opportunity to identify and target disease pathways. This review highlights some important metabolic alterations detected in neurodegeneration caused by misfolded prion protein and discusses common toxicity pathways identified across different neurodegenerative diseases. Thus, having established some commonalities between various degenerative conditions, detectable metabolic changes may be of extreme value as an early diagnostic biomarker in disease.
文摘Globally, the third cause of males cancer and the fourth cause of females cancer is colon cancer(CC). In Egypt, high CC percentage occurs in children and in individuals below 40 years of age. The complete loss of biological enzyme function is the main cause of CC and consequently CC increased in smoking and pollution exposure. The aim of this review is to focus on the application of metabolome as a physiological tool that can play an important role in preventing CC incidence by natural products and hormones. The dietary factors, intestinal micro-flora and endogenously produced metabolites are the main three causes that produce free radicals in the colon. A correlation occurs between the enzyme activity and CC polymorphisms or property. Nowadays metabolome is applied with the progress of different analytical methods, data bases and tools for cancer predication and stimulation especially in CC cases. Metabolism is defined as intracellular chemical reactions that produce chemical substances and energies sustaining life. Metabolic pathway networks are also composed of links that are defined as transformation of chemical structures between two metabolites and an enzyme reaction. The most important advantage of metabolome is its ability to analyze metabolites from any source, regardless of origin, where the application of liquid chromatography combined with mass spectra in metabolome analysis to a series of cancer cell lines that were progressively more tumorigenic due to the induction of 1,2,3 or 4 oncogenes to cell lines could be a metabolome example application. In conclusion, natural products and hormones are very important in preventing CC in humans and animal models where both natural products and hormones play a significant and important effect in regulating physiological process especially in CC cases. In this situation, metabolome must increase in its application in the future for the diagnosis of CC cases.
