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
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
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
Identifying chemical structures inhuman-derived samples presents significant challenges due to limited structural data obtained from untargeted metabolomics studies.When the chemical structures of molecules are closel...Identifying chemical structures inhuman-derived samples presents significant challenges due to limited structural data obtained from untargeted metabolomics studies.When the chemical structures of molecules are closely related to the phenotypic status of human ecosystems,it becomes invaluable to devise a method for efficiently and systematically determining structures that correlate with the pathophysiological status of humans in a high-throughput approach.展开更多
This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses...This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses and modulated key indicators of antioxidant capacity.Moreover,the down-regulation of critical proteins of the Nrf2 pathway induced by Pb could be reversed after NCVP intervention.In addition,NCVP maintained the diversity of gut bacteriobiota and restored the relative abundance of f_Prevotellaceae,g_Alloprevotella,and f_Eubacterium_coprostanoligenes_group reduced by Pb.Also,NCVP regulated the diversity and abundance of gut mycobiota affected by Pb.Specifically,Pb decreased the proportion of pathogenic species(g_Fusarium,p_Basidiomycota,g_Alternaria,g_Aspergillus,and g_Candida)while NCVP increased the abundance of probiotics species(g_Kazachstania and p_Ascomycota).Furthermore,the metabolomic analysis found that NCVP significantly altered a range of microbial metabolites,including porphobilinogen,cromakalim,salidroside,and trichostatin A,which has significant associations with specific gut bacteriobiota or mycobiota.These altered metabolites are involved in primary bile acid biosynthesis,metabolism of xenobiotics by cytochrome P450,lysine degradation,and other metabolic pathways.Overall,our findings indicate that NCVP might be an excellent natural product for eliminating Pb-induced hepatorenal toxicity,possibly by regulating gut bacteriome,mycobiome and metabolome.展开更多
Anoplophora glabripennis is one of the most devastating wood-boring beetles that attacks poplars.However,one poplar species,Populus deltoides,has strong resistance to Anoplophora glabripennis infestation,the underlyin...Anoplophora glabripennis is one of the most devastating wood-boring beetles that attacks poplars.However,one poplar species,Populus deltoides,has strong resistance to Anoplophora glabripennis infestation,the underlying defense mechanisms against Anoplophora glabripennis are poorly understood.Secondary metabolites play a crucial role in plants to combat biological stress.Here,based on transcriptome and metabolome,we demonstrated that the mechanisms for responses to mechanical damage and insect infestation were different.The degree of reactions to adult groove production,larval incubation,and larval frass production was not identical.In addition,the potential genes with insect resistance activity were identified.Predominant differentially expressed genes(DEGs)found in the phloem of Populus deltoides include anthocyanidin 3-O-glucosyltransferase5(PdUGT72E),peroxidase 73(PdPod73),peroxidase A2(PdPodA2)and macrophage migration inhibitory factor(PdMIF)responded to stress caused by Anoplophora glabripennis,which further resulted in activation of the plant defense system against insects via changes in regulation of metabolic pathways,such as tyrosine metabolism pathway,phenylpropanoid biosynthesis pathway and flavonoid biosynthesis pathway.Therefore,this work has laid a foundation for further unraveling the mechanisms involved in this interaction.展开更多
Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precurs...Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.展开更多
Lycium barbarum residue(LBR),a by-product of L.barbarum processing,is packed with bioactive components and can be potentially utilized as a feed additive in animal husbandry.However,the fundamental understanding of it...Lycium barbarum residue(LBR),a by-product of L.barbarum processing,is packed with bioactive components and can be potentially utilized as a feed additive in animal husbandry.However,the fundamental understanding of its effectiveness on livestock animals is still lacking,particularly in ruminants.To explore the effects of LBR on the growth performance,rumen fermentation parameters,ruminal microbes and metabolites of Tan sheep,sixteen fattening rams(aged 4 mon)were fed a basal diet(CON,n=8)or a basal diet supplemented with 5%LBR(LBR,n=8).The experiment lasted for 70 d,with 10 d adaptation period and 60 d treatment period.The results showed that the LBR enhanced the average daily feed intake,average daily gain(P<0.05),and ruminal total volatile fatty acids(P<0.01)while decreasing ammonia-nitrogen concentration and rumen pH value(P<0.05).Additionally,the LBR improved the relative abundances of Prevotella,Succiniclasticum,Ruminococcus,Coprococcus,Selenomonas,and Butyrivibrio(P<0.05)and reduced the relative abundances of Oscillospira and Succinivibrio(P<0.05).The LBR altered the ruminal metabolome(P<0.01)by increasing the abundances of ruminal metabolites involved in amino acids(e.g.,L-proline,L-phenylalanine,L-lysine,and L-tyrosine),pyrimidine metabolism(e.g.,uridine,uracil,and thymidine),and microbial protein synthesis(e.g.,xanthine and hypoxanthine).In conclusion,LBR had positive effects on the growth rate of Tan sheep as well as on rumen fermentation parameters,rumen microbiome and rumen metabolome.展开更多
Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to...Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.展开更多
Chronic kidney disease(CKD)is an increasingly prevalent medical condition associated with high mortality and cardiovascular complications.The intricate interplay between kidney dysfunction and subsequent metabolic dis...Chronic kidney disease(CKD)is an increasingly prevalent medical condition associated with high mortality and cardiovascular complications.The intricate interplay between kidney dysfunction and subsequent metabolic disturbances may provide insights into the underlying mechanisms driving CKD onset and progression.Herein,we proposed a large-scale plasma metabolite identification and quantification system that combines the strengths of targeted and untargeted metabolomics technologies,i.e.,widely-targeted metabolomics(WT-Met)approach.WT-Met method enables large-scale identification and accurate quantification of thousands of metabolites.We collected plasma samples from 21 healthy controls and 62CKD patients,categorized into different stages(22 in stages 1-3,20 in stage 4,and 20 in stage 5).Using LC-MS-based WT-Met approach,we were able to effectively annotate and quantify a total of 1431metabolites from the plasma samples.Focusing on the 539 endogenous metabolites,we identified 399significantly altered metabolites and depicted their changing patterns from healthy controls to end-stage CKD.Furthermore,we employed machine-learning to identify the optimal combination of metabolites for predicting different stages of CKD.We generated a multiclass classifier consisting of 7 metabolites by machine-learning,which exhibited an average AUC of 0.99 for the test set.In general,amino acids,nucleotides,organic acids,and their metabolites emerged as the most significantly altered metabolites.However,their patterns of change varied across different stages of CKD.The 7-metabolite panel demonstrates promising potential as biomarker candidates for CKD.Further exploration of these metabolites can provide valuable insights into their roles in the etiology and progression of CKD.展开更多
Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficie...Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.展开更多
The use of biochar can have several effects on plant germination,depending on raw material,preparation method and application dose.However,the molecular mechanisms that lead to those results have yet to be elucidated....The use of biochar can have several effects on plant germination,depending on raw material,preparation method and application dose.However,the molecular mechanisms that lead to those results have yet to be elucidated.The aim of this research was to improve the understanding of these mechanisms by characterizing the metabolic effects of sugarcane bagasse biochar on soybean germination.Three types of biochars were prepared by pyrolysis at 300℃(SCB300),400℃(SCB400)and 600℃(SCB600).Then,each one was mixed into sand at 1%,3%,5%(w/w)dose,respectively.The experiment was performed in 8 days of incubation,when the number of germinated seeds and the average radicle length were determined.To evaluate the metabolome,the dry biomass(DB)was subjected to extraction with a mixture of methanol-d4 and D2O(1:1 v/v).The extracts were submitted to metabolomics analysis by Proton Nuclear Magnetic Resonance.The Relative Germination,Relative Average Radicle Growth and Germination Index increased in all treatments compared to control.On the other hand,the DB increased in all treatments,except for SCB300,at doses of 1%and 3%w/w.Seven metabolites(alanine,asparagine,acetic acid,citric acid,glycerol,fatty acids and sucrose)were identified and quantified in DB extracts as the most influential finding for the separation of treatments.Taken together,these results strongly suggested that biochars accelerated the catabolism of triacylglycerols to sucrose and induced a slight osmotic stress.展开更多
Background The hypothalamus plays a crucial role in the health and productivity of dairy cows,yet studies on its fun ctionality and its impact on peripheral circulation in these animals are relatively scarce,particula...Background The hypothalamus plays a crucial role in the health and productivity of dairy cows,yet studies on its fun ctionality and its impact on peripheral circulation in these animals are relatively scarce,particularly regarding dietary interventions.Therefore,our study undertook a comprehensive analysis,incorporating both metabolomics and transcriptomics,to explore the effects of a grain-based diet on the functionality of the hypothalamus,as well as on blood and milk in dairy cows.Results The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E_(2)(PGE_(2))level as a prominent response to the grain-based diet introduction.Furthermore,the hypothalamic transcriptome profiling showed a nota ble upregulation in amino acid metabolism due to the grain-based diet.Conversely,the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE_(2),including phospholipase A2(PLA2G4E,PLA2G2A,and PLA2G12B),cyclooxygenase-2(COX2),and prostaglandin E synthase(PTGES).Additionally,the plasma metabolome analysis indicated a substantial decrease in the level of PGE_(2),along with a decline in adrenal steroid hormones(tetrahydrocortisol and pregnenolone)following the grain-based diet introduction.Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE_(2)level.Importantly,PGE_(2)was identified as a critical metabolic marker in the hypothalamus,blood,and milk in response to grain intervention.Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus,blood,and milk following the grain-based diet.Conclusions Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.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
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.
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 the National Natural Science Foundation of China(Nos.81930109 and 82321005)。
文摘Identifying chemical structures inhuman-derived samples presents significant challenges due to limited structural data obtained from untargeted metabolomics studies.When the chemical structures of molecules are closely related to the phenotypic status of human ecosystems,it becomes invaluable to devise a method for efficiently and systematically determining structures that correlate with the pathophysiological status of humans in a high-throughput approach.
基金supported by the Program of the National Natural Science Foundation of China(31872519)General Project of Jilin Provincial Department of Science and Technology(20230101247JC)the Open Research Fund of Engineering Research Center of Bioreactor and Pharmaceutical Development,Ministry of Education.(KF202002).
文摘This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses and modulated key indicators of antioxidant capacity.Moreover,the down-regulation of critical proteins of the Nrf2 pathway induced by Pb could be reversed after NCVP intervention.In addition,NCVP maintained the diversity of gut bacteriobiota and restored the relative abundance of f_Prevotellaceae,g_Alloprevotella,and f_Eubacterium_coprostanoligenes_group reduced by Pb.Also,NCVP regulated the diversity and abundance of gut mycobiota affected by Pb.Specifically,Pb decreased the proportion of pathogenic species(g_Fusarium,p_Basidiomycota,g_Alternaria,g_Aspergillus,and g_Candida)while NCVP increased the abundance of probiotics species(g_Kazachstania and p_Ascomycota).Furthermore,the metabolomic analysis found that NCVP significantly altered a range of microbial metabolites,including porphobilinogen,cromakalim,salidroside,and trichostatin A,which has significant associations with specific gut bacteriobiota or mycobiota.These altered metabolites are involved in primary bile acid biosynthesis,metabolism of xenobiotics by cytochrome P450,lysine degradation,and other metabolic pathways.Overall,our findings indicate that NCVP might be an excellent natural product for eliminating Pb-induced hepatorenal toxicity,possibly by regulating gut bacteriome,mycobiome and metabolome.
基金supported by the National Natural Science Foundation of China(Nos.32271891 and 32171798).
文摘Anoplophora glabripennis is one of the most devastating wood-boring beetles that attacks poplars.However,one poplar species,Populus deltoides,has strong resistance to Anoplophora glabripennis infestation,the underlying defense mechanisms against Anoplophora glabripennis are poorly understood.Secondary metabolites play a crucial role in plants to combat biological stress.Here,based on transcriptome and metabolome,we demonstrated that the mechanisms for responses to mechanical damage and insect infestation were different.The degree of reactions to adult groove production,larval incubation,and larval frass production was not identical.In addition,the potential genes with insect resistance activity were identified.Predominant differentially expressed genes(DEGs)found in the phloem of Populus deltoides include anthocyanidin 3-O-glucosyltransferase5(PdUGT72E),peroxidase 73(PdPod73),peroxidase A2(PdPodA2)and macrophage migration inhibitory factor(PdMIF)responded to stress caused by Anoplophora glabripennis,which further resulted in activation of the plant defense system against insects via changes in regulation of metabolic pathways,such as tyrosine metabolism pathway,phenylpropanoid biosynthesis pathway and flavonoid biosynthesis pathway.Therefore,this work has laid a foundation for further unraveling the mechanisms involved in this interaction.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202001)the National Natural Science Foundation of China(82104835).
文摘Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.
基金supported by the National Key Research and Development Program of China(2022YFD1300905)the National Natural Science Foundation of China(31960672)+3 种基金the Key Research and Development Program of Ningxia Hui Autonomous Region,China(2021BEF02020)the Top Discipline Construction Project of Pratacultural Science(NXYLXK2017A01)the Science and Technology Development Project of Jilin Province,China(20200201140JC)the Technology Cooperation High-Tech Industrialization Project of Jilin Province,China and the Chinese Academy of Sciences,(2022SYHZ0020).
文摘Lycium barbarum residue(LBR),a by-product of L.barbarum processing,is packed with bioactive components and can be potentially utilized as a feed additive in animal husbandry.However,the fundamental understanding of its effectiveness on livestock animals is still lacking,particularly in ruminants.To explore the effects of LBR on the growth performance,rumen fermentation parameters,ruminal microbes and metabolites of Tan sheep,sixteen fattening rams(aged 4 mon)were fed a basal diet(CON,n=8)or a basal diet supplemented with 5%LBR(LBR,n=8).The experiment lasted for 70 d,with 10 d adaptation period and 60 d treatment period.The results showed that the LBR enhanced the average daily feed intake,average daily gain(P<0.05),and ruminal total volatile fatty acids(P<0.01)while decreasing ammonia-nitrogen concentration and rumen pH value(P<0.05).Additionally,the LBR improved the relative abundances of Prevotella,Succiniclasticum,Ruminococcus,Coprococcus,Selenomonas,and Butyrivibrio(P<0.05)and reduced the relative abundances of Oscillospira and Succinivibrio(P<0.05).The LBR altered the ruminal metabolome(P<0.01)by increasing the abundances of ruminal metabolites involved in amino acids(e.g.,L-proline,L-phenylalanine,L-lysine,and L-tyrosine),pyrimidine metabolism(e.g.,uridine,uracil,and thymidine),and microbial protein synthesis(e.g.,xanthine and hypoxanthine).In conclusion,LBR had positive effects on the growth rate of Tan sheep as well as on rumen fermentation parameters,rumen microbiome and rumen metabolome.
基金funds by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS),China(Grant No.:2022-I2M-1e014)the National Natural Science Foundation of China(Grant No.:82293684)+1 种基金Beijing Natural Science Foundation,China(Grant No.:L232084)the National Key R&D Program of China(Grant No.:2022YFA0806400).
文摘Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.
基金supported by the National Key R&D Program of China(Nos.2022YFC3400700,2022YFA0806600)the Key Research and Development Project of Hubei Province(No.2023BCB094)+1 种基金the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University(No.JCRCGW-2022-008)the Key Laboratory of Hubei Province(No.2021KFY005)。
文摘Chronic kidney disease(CKD)is an increasingly prevalent medical condition associated with high mortality and cardiovascular complications.The intricate interplay between kidney dysfunction and subsequent metabolic disturbances may provide insights into the underlying mechanisms driving CKD onset and progression.Herein,we proposed a large-scale plasma metabolite identification and quantification system that combines the strengths of targeted and untargeted metabolomics technologies,i.e.,widely-targeted metabolomics(WT-Met)approach.WT-Met method enables large-scale identification and accurate quantification of thousands of metabolites.We collected plasma samples from 21 healthy controls and 62CKD patients,categorized into different stages(22 in stages 1-3,20 in stage 4,and 20 in stage 5).Using LC-MS-based WT-Met approach,we were able to effectively annotate and quantify a total of 1431metabolites from the plasma samples.Focusing on the 539 endogenous metabolites,we identified 399significantly altered metabolites and depicted their changing patterns from healthy controls to end-stage CKD.Furthermore,we employed machine-learning to identify the optimal combination of metabolites for predicting different stages of CKD.We generated a multiclass classifier consisting of 7 metabolites by machine-learning,which exhibited an average AUC of 0.99 for the test set.In general,amino acids,nucleotides,organic acids,and their metabolites emerged as the most significantly altered metabolites.However,their patterns of change varied across different stages of CKD.The 7-metabolite panel demonstrates promising potential as biomarker candidates for CKD.Further exploration of these metabolites can provide valuable insights into their roles in the etiology and progression of CKD.
基金supported by the National Natural Science Foundation of China(Grant Nos.32030099 and 32072670)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA28020301)+1 种基金the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.2023326)the Enterprise Cooperation Projects of China(Grant No.Am20210407RD).
文摘Biological nitrification inhibitors(BNIs)are released from plant roots and inhibit the nitrification activity of microorganisms in soils,reducing NO_(3)^(‒)leaching and N2O emissions,and increasing nitrogenuse efficiency(NUE).Several recent studies have focused on the identification of new BNIs,yet little is known about the genetic loci that govern their biosynthesis and secretion.We applied a combined transcriptomic and metabolomic analysis to investigate possible biosynthetic pathways and transporters involved in the biosynthesis and release of BNI 1,9-decanediol(1,9-D),which was previously identified in rice root exudates.Our results linked four fatty acids,icosapentaenoic acid,linoleate,norlinolenic acid,and polyhydroxy-α,ω-divarboxylic acid,with 1,9-D biosynthesis and three transporter families,namely the ATP-binding cassette protein family,the multidrug and toxic compound extrusion family,and the major facilitator superfamily,with 1,9-D release from roots into the soil medium.Our finding provided candidates for further work on the genes implicated in the biosynthesis and secretion of 1,9-D and pinpoint genetic loci for crop breeding to improve NUE by enhancing 1,9-D secretion,with the potential to reduce NO_(3)^(‒)leaching and N2O emissions from agricultural soils.
基金Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nível Superior (CAPES), Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG [grant number APQ-02349-21])Universidade do Estado de Minas Gerais (UEMG [Productivity Researcher of the UEMG – PQ/UEMG]) for their financial support and fellowships
文摘The use of biochar can have several effects on plant germination,depending on raw material,preparation method and application dose.However,the molecular mechanisms that lead to those results have yet to be elucidated.The aim of this research was to improve the understanding of these mechanisms by characterizing the metabolic effects of sugarcane bagasse biochar on soybean germination.Three types of biochars were prepared by pyrolysis at 300℃(SCB300),400℃(SCB400)and 600℃(SCB600).Then,each one was mixed into sand at 1%,3%,5%(w/w)dose,respectively.The experiment was performed in 8 days of incubation,when the number of germinated seeds and the average radicle length were determined.To evaluate the metabolome,the dry biomass(DB)was subjected to extraction with a mixture of methanol-d4 and D2O(1:1 v/v).The extracts were submitted to metabolomics analysis by Proton Nuclear Magnetic Resonance.The Relative Germination,Relative Average Radicle Growth and Germination Index increased in all treatments compared to control.On the other hand,the DB increased in all treatments,except for SCB300,at doses of 1%and 3%w/w.Seven metabolites(alanine,asparagine,acetic acid,citric acid,glycerol,fatty acids and sucrose)were identified and quantified in DB extracts as the most influential finding for the separation of treatments.Taken together,these results strongly suggested that biochars accelerated the catabolism of triacylglycerols to sucrose and induced a slight osmotic stress.
基金funded by Natural Science Foundation of China(32072755)。
文摘Background The hypothalamus plays a crucial role in the health and productivity of dairy cows,yet studies on its fun ctionality and its impact on peripheral circulation in these animals are relatively scarce,particularly regarding dietary interventions.Therefore,our study undertook a comprehensive analysis,incorporating both metabolomics and transcriptomics,to explore the effects of a grain-based diet on the functionality of the hypothalamus,as well as on blood and milk in dairy cows.Results The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E_(2)(PGE_(2))level as a prominent response to the grain-based diet introduction.Furthermore,the hypothalamic transcriptome profiling showed a nota ble upregulation in amino acid metabolism due to the grain-based diet.Conversely,the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE_(2),including phospholipase A2(PLA2G4E,PLA2G2A,and PLA2G12B),cyclooxygenase-2(COX2),and prostaglandin E synthase(PTGES).Additionally,the plasma metabolome analysis indicated a substantial decrease in the level of PGE_(2),along with a decline in adrenal steroid hormones(tetrahydrocortisol and pregnenolone)following the grain-based diet introduction.Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE_(2)level.Importantly,PGE_(2)was identified as a critical metabolic marker in the hypothalamus,blood,and milk in response to grain intervention.Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus,blood,and milk following the grain-based diet.Conclusions Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet.
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.
