Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and...Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability.In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy.Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms,including the production of metabolites,such as short-chain fatty acids(SCFAs),tryptophan derivatives,and extracellular polysaccharides that remodel the tumor microenvironment,as well as the activation of immune pathways involving dendritic cells,CD8+T cells,and M1 macrophages to increase antitumor immunity.Moreover,clinical studies have shown that fecal microbiota transplantation(FMT)and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy,while reducing the risk of immune-related adverse events(irAEs).This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies.The integration of multiomics technologies,synthetic biology,and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by...Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.展开更多
Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut...Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut and the central nervous system.More importantly,mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain.Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases.Mitochondria are essential for meeting the host’s substantial neuronal metabolic demands,maintaining excitability,and facilitating synaptic transmission.Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases.Therefore,this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration,as well as the existing potential therapeutic strategies for neurodegenerative disorders.These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases,and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases.However,this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases,such as Huntington’s disease and Multiple sclerosis,and the potential therapeutic strategies were translated into clinical trials,which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compo...Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.展开更多
Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extr...Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.展开更多
Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)h...Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.展开更多
Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicke...Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.展开更多
This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L....This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L.reuteri CCFM1132(n=34)or placebo(n=31)daily for 8 weeks.After the intervention,serum UA concentration significantly decreased,along with a reduction in xanthine oxidase(XOD)activity compared to the placebo group(P<0.01).Indicators of liver(aspartate transaminase and alanine transaminase)and renal(urea and creatinine)functions improved.Short-chain fatty acid(SCFA)concentrations significantly increased,with an upregulated abundance of SCFA producers(Fusicatenibacter,Ruminococcaceae UCG_014,and Ruminococcus 1)in the gut.Additionally,correlation analysis revealed that concentrations of SCFAs,particularly acetate and butyrate,were strongly negatively correlated with UA concentration and XOD activity.These findings suggest that L.reuteri CCFM1132 relieves hyperuricemia by enhancing the abundance of SCFA producers in the gut to promote SCFA production and by suppressing XOD activity.This study provides a valuable reference for developing new treatments for hyperuricemia.展开更多
Understanding how diet and host phylogeny shape gut microbiota is fundamental to elucidating host-microbe interactions in extreme environments.The Qinghai-Tibet Plateau(QTP),characterized by harsh conditions,provides ...Understanding how diet and host phylogeny shape gut microbiota is fundamental to elucidating host-microbe interactions in extreme environments.The Qinghai-Tibet Plateau(QTP),characterized by harsh conditions,provides a natural laboratory for examining these relationships among sympatric species.Here,we investigated the dietary composition and gut microbiota of six passerine species inhabiting the QTP,comprising two endemic residents(White-rumped Snowfinch Onychostruthus taczanowskii and Ground Tit Pseudopodoces humilis),two nonendemic residents(Rock Sparrow Petronia petronia and Eurasian Tree Sparrow Passer montanus),and two nonendemic migratory species(Twite Linaria flavirostris and Black Redstart Phoenicurus ochruros),using highthroughput 18S and 16S rRNA sequencing.Our results revealed that dietary composition—dominated by Archaeplastida,Metazoa,Fungi,and the SAR supergroup—exhibited no significant interspecific variation,reflecting a high degree of trophic niche overlap.Although the overall diet was similar across species,the relative abundances of certain dietary components independently influenced specific microbial taxa.In particular,dietary Archaeplastida and Fungi showed phylogeny-independent positive correlations with 16 and 3 microbial genera,respectively,revealing fine-scale diet-microbiota associations.Evidence of phylosymbiosis was detected,as closely related species harbored more similar microbial communities driven by species-specific microbial biomarkers.Notably,our results suggested deterministic processes played a stronger role in endemic species,whereas stochastic community assembly dominated in non-endemic species,indicating distinct assembly mechanisms shaped by biogeographic history.Overall,this study reveals that while dietary similarity promotes convergent trophic niches among sympatric passerines,host phylogeny exerts a stronger influence on gut microbiota composition and assembly.These findings underline the synergistic roles of diet-microbiota interactions and phylosymbiosis dynamics as key adaptive strategies that enable birds to cope with the extreme environments of the QTP.展开更多
Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight ...Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.展开更多
Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)ha...Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.展开更多
Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the undere...Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.展开更多
Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular ...Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular disease risk,including atrial fibrillation,myocardial infarction,chronic heart failure,and hypertension.Methods We analyzed GWAS data from East Asian populations'oral microbiome,involving 2,017 tongue and 1,915 saliva samples from 2,984 individuals with whole-genome sequencing.Additionally,we sourced cardiovascular disease GWAS data from NBDC,including atrial fibrillation(8,180 cases,28,621 controls),myocardial infarction(14,992 cases,146,214 controls),chronic heart failure(10,540 cases,168,186 controls),and systolic blood pressure(145,505 individuals).Results Several oral microbiota taxa were found to be significantly associated with cardiovascular disease outcomes.Specific microbiota,such as Centipeda,Corynebacterium,and Pseudomonas E,were negatively correlated with heart failure.In contrast,taxa like Neisseria D and Actinomyces were associated with an increased risk of atrial fibrillation and myocardial infarction.Additionally,certain oral microbiota showed correlations with changes in blood pressure,highlighting their potential role in hypertension.Conclusion Our findings suggest that the oral microbiota may influence the development and progression of cardiovascular diseases,providing new insights into the potential impact of oral health on cardiovascular risk.展开更多
Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementat...Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.展开更多
The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a se...The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.展开更多
Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxa...Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.展开更多
Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivar...Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.展开更多
Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-infla...Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82222058,82425046,and 82273142).
文摘Anti-programmed cell death protein 1(PD-1)or its ligand(PD-L1)are immune checkpoint inhibitors(ICIs)that have revolutionized cancer therapy.However,the efficacy of anti-PD-1 and anti-PD-L1 is limited by resistance and inter-individual variability.In recent years increasing evidence has highlighted the pivotal role of the gut microbiota in modulating the response to PD-1/PD-L1 immunotherapy.Extensive preclinical studies have demonstrated that commensal microbes can increase the efficacy of PD-1/PD-L1 blockade through multiple mechanisms,including the production of metabolites,such as short-chain fatty acids(SCFAs),tryptophan derivatives,and extracellular polysaccharides that remodel the tumor microenvironment,as well as the activation of immune pathways involving dendritic cells,CD8+T cells,and M1 macrophages to increase antitumor immunity.Moreover,clinical studies have shown that fecal microbiota transplantation(FMT)and targeted probiotic interventions show promise for improving the response to PD-1/PD-L1 therapy,while reducing the risk of immune-related adverse events(irAEs).This review systematically explores the multifaceted regulatory roles of the commensal microbiota in PD-1/PD-L1 therapy and examines the preclinical prospects of microbiota-based personalized immunotherapeutic strategies.The integration of multiomics technologies,synthetic biology,and precise microbiota interventions may further optimize PD-1/PD-L1 immunotherapy and offer novel insights into antitumor immune modulation.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金the 2026 Health Commission Fund of Guizhou Province,China.the freestatistics suite for its technical support.
文摘Helicobacter pylori(H.pylori)infection remains a pivotal driver of chronic gastritis,peptic ulcer,gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer,yet its eradication is increasingly frustrated by climbing antibiotic resistance and intolerable side-effects of standard triple or quadruple therapies.In recent years,fecal microbiota transplantation(FMT),a strategy that reconstructs the gut ecosystem by introducing a healthy donor microbiome,has emerged as a novel adjunct or alternative.By competitively excluding H.pylori,reinforcing mucosal barrier integrity,modulating host immunity and secreting bacteriocins,FMT can raise eradication rates,relieve dyspeptic symptoms and lower recurrence.This review synthesizes up-to-date pre-clinical,pilot and controlled clinical data,dissects underlying mechanisms,compares delivery routes,donor screening protocols and safety profiles,and discusses regulatory,ethical and standardization hurdles that must be overcome before large-scale clinical application.
基金supported by General Program of National Natural Science Foundation of China,No.82370986(to LAW)Shaanxi Provincial NaturalScience Foundation Key Project,No.2023-JC-ZD-56(to SS).
文摘Emerging evidence suggests that the gut microbiota is closely associated with the pathological manifestations of multiple neurodegenerative diseases via the gut-brain axis,which refers to the crosstalk between the gut and the central nervous system.More importantly,mitochondria have been considered prominent mediators of the interplay between the gut microbiota and the brain.Intestinal microbes may modulate mitochondrial function in the central nervous system to affect the progression of neurodegenerative diseases.Mitochondria are essential for meeting the host’s substantial neuronal metabolic demands,maintaining excitability,and facilitating synaptic transmission.Dysfunctional mitochondria are considered critical hallmarks of various neurodegenerative diseases.Therefore,this review provides novel insights into the intricate roles of gut microbiota-mitochondrial crosstalk in the underlying mechanisms during the progression of neurodegeneration,as well as the existing potential therapeutic strategies for neurodegenerative disorders.These suggest intestinal microbiota-mitochondrial interaction play a crucial role in the occurrence and development of neurodegenerative diseases,and targeting this interaction may be a promising therapeutic approach to neurodegenerative diseases.However,this review found that there was relatively little research on the effect of this crosstalk on other neurodegenerative diseases,such as Huntington’s disease and Multiple sclerosis,and the potential therapeutic strategies were translated into clinical trials,which face many challenges in developing personalized treatment plans based on the unique gut microbiota of different individuals.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金funded by the National Natural Science Foundation of China(32101915)Natural Science Foundation of Jiangxi Province(20224BAB205005)+1 种基金Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province(20232BCJ23090)Natural Science Foundation of Chongqing(CSTB2023NSCQMSX0497).
文摘Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.
基金financially supported by the Natural Science Foundation of Zhejiang Province(LY22C010002)China Postdoctoral Science Foundation(2022M721732)+1 种基金the project of sending sci-tech experts to rural areas in Ningbo city(2022S205)the K.C.Wong Magna Fund of Ningbo University.
文摘Artemisia argyi(A.argyi)is a Chinese herbal medicine with reported anti-inflammatory effects.In this study,the A.argyi was extracted with water and ethanol,and the concentrations of 35 flavonoids in A.argyi water extract(WE)and ethanol extract(EE)were measured via targeted metabolomics.The antioxidant and antiinflammatory activities of both WE and EE were firstly explored in vitro via chemical assays and cellular experiment,respectively.Both WE and EE showed significant 1,1-diphenyl-2-picrylhydrazyl(DPPH),2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),·OH,and O_(2)·radical scavenging ability in a dose-dependent manner,and reduced the levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and interleukin-22(IL-22)in lipopolysaccharide(LPS)induced RAW264.7 cell model.In addition,the in vivo anti-colitis activity of both extracts was investigated in dextran sulfate sodium(DSS)-induced colitis mice,and the underlying mechanisms were elucidated by 16S r DNA sequencing and targeted metabolomics.We found that both WE and EE relieved colitis in mice,characterized by decreased disease activity index,increased colon length,improved pathological changes in colon tissue,while EE showed better anti-colitis activity.In addition,both 16S r DNA sequencing and targeted bile acids metabolomics indicated EE modulated gut microbiota and specifically increased the abundance of lithocholic acid(LCA),which might contribute to intestinal barrier function improvement via up-regulating the expression of colonic farnesoid X receptor(FXR).In summary,this study identified the anti-colitis mechanism of A.argyi EE by modulating gut microbiota,facilitating the production of LCA,activating FXR and improving intestinal barrier function.
基金Supported by the Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University,No.CX2023021.
文摘Acute pancreatitis(AP)is sudden inflammation of the pancreas,which can lead to multiple organ dysfunction in severe cases.Hypertriglyceridemia(HTG)is the third most common cause.In recent years,HTG-induced AP(HTG-AP)has garnered increasing attention.Compared to AP caused by other causes,HTG-AP often has a more subtle onset but is more likely to progress to a severe,critical illness that poses a serious threat to a patient’s life and health.Research suggests a potential connection between the gut microbiota and AP,which could be mediated by bacterial metabolites,immune cells,and inflammatory factors.This is supported by observations of microbial imbalance and higher intestinal permeability in patients with AP.In addition,studies have shown that HTG-induced changes in gut microbiota can worsen AP by negatively impacting the host metabolism,immune response,and function of the intestinal barrier.In this review,we summarize recent clinical and animal studies on the role and mechanism of gut microbiota in the severity of AP aggravated by HTG.The application prospects of the newly proposed microbial-host-isozyme concept are summarized,focusing on its potential for the precision diagnosis and treatment of HTG-AP through gut microbiota regulation.
基金funded by the National Key Research&Development Program of China(2023YFD1301400 and 2023YFF1001900)the Program for Shaanxi Science&Technology(2022GD-TSLD-46-0302,2023KXJ-243,2023GXJS-02-01 and L2022-QCYZX-NY-004)。
文摘Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.
基金This work was supported by the National Natural Science Foundation of China(32272332,32021005)the Fundamental Research Funds for the Central Universities(JUSRP622020,JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province.
文摘This randomized,double-blind,placebo-controlled trial evaluated the uric acid(UA)-lowering effect of Limosilactobacillus reuteri CCFM1132 in young males with hyperuricemia.Participants received 1×10^(10)CFU of L.reuteri CCFM1132(n=34)or placebo(n=31)daily for 8 weeks.After the intervention,serum UA concentration significantly decreased,along with a reduction in xanthine oxidase(XOD)activity compared to the placebo group(P<0.01).Indicators of liver(aspartate transaminase and alanine transaminase)and renal(urea and creatinine)functions improved.Short-chain fatty acid(SCFA)concentrations significantly increased,with an upregulated abundance of SCFA producers(Fusicatenibacter,Ruminococcaceae UCG_014,and Ruminococcus 1)in the gut.Additionally,correlation analysis revealed that concentrations of SCFAs,particularly acetate and butyrate,were strongly negatively correlated with UA concentration and XOD activity.These findings suggest that L.reuteri CCFM1132 relieves hyperuricemia by enhancing the abundance of SCFA producers in the gut to promote SCFA production and by suppressing XOD activity.This study provides a valuable reference for developing new treatments for hyperuricemia.
基金supported by the National Key Research and Development Program of China(2024YFC2310303)the National Natural Science Foundation of China(NSFC,No.32471572)awarded to D.L.+1 种基金NSFC(No.32171490)awarded to Y.W.Hebei Natural Science Foundation(HNSF,C2021204059)awarded to Y.S。
文摘Understanding how diet and host phylogeny shape gut microbiota is fundamental to elucidating host-microbe interactions in extreme environments.The Qinghai-Tibet Plateau(QTP),characterized by harsh conditions,provides a natural laboratory for examining these relationships among sympatric species.Here,we investigated the dietary composition and gut microbiota of six passerine species inhabiting the QTP,comprising two endemic residents(White-rumped Snowfinch Onychostruthus taczanowskii and Ground Tit Pseudopodoces humilis),two nonendemic residents(Rock Sparrow Petronia petronia and Eurasian Tree Sparrow Passer montanus),and two nonendemic migratory species(Twite Linaria flavirostris and Black Redstart Phoenicurus ochruros),using highthroughput 18S and 16S rRNA sequencing.Our results revealed that dietary composition—dominated by Archaeplastida,Metazoa,Fungi,and the SAR supergroup—exhibited no significant interspecific variation,reflecting a high degree of trophic niche overlap.Although the overall diet was similar across species,the relative abundances of certain dietary components independently influenced specific microbial taxa.In particular,dietary Archaeplastida and Fungi showed phylogeny-independent positive correlations with 16 and 3 microbial genera,respectively,revealing fine-scale diet-microbiota associations.Evidence of phylosymbiosis was detected,as closely related species harbored more similar microbial communities driven by species-specific microbial biomarkers.Notably,our results suggested deterministic processes played a stronger role in endemic species,whereas stochastic community assembly dominated in non-endemic species,indicating distinct assembly mechanisms shaped by biogeographic history.Overall,this study reveals that while dietary similarity promotes convergent trophic niches among sympatric passerines,host phylogeny exerts a stronger influence on gut microbiota composition and assembly.These findings underline the synergistic roles of diet-microbiota interactions and phylosymbiosis dynamics as key adaptive strategies that enable birds to cope with the extreme environments of the QTP.
基金funded by the National Natural Science Foundation of China(Grant No.82470766 to H.M.)the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(Grant No.JSDW202206 to C.X.)the First Affiliated Hospital of Nanjing Medical University Clinical Capacity Enhancement Project(Grant No.JSPH-MC-2022-18 to C.X.).
文摘Acute kidney injury(AKI)is a critical condition with limited effective therapies.Akkermansia muciniphila(A.muciniphila)is a probiotic with multiple beneficial effects,including the regulation of epithelial cell tight junctions.Since renal pathophysiology is associated with gut barrier integrity,we hypothesized that A.muciniphila may have preventive effects on AKI.We established a lipopolysaccharide(LPS)-induced AKI mouse model to evaluate the effects of A.muciniphila.Our findings showed that pretreatment with A.muciniphila significantly attenuated kidney injury,as evidenced by reduced serum creatinine and urea nitrogen levels,alongside decreased tubular necrosis and apoptosis.A.muciniphila preserved intestinal barrier integrity and induced marked shifts in gut microbial ecology and the metabolome.A.muciniphila notably induced an increase in the relative abundance of the phylum Proteobacteria while decreasing in that of the phylum Bacteroidetes.At the genus level,Prevotella,Faecalibaculum,Moraxella,and Lactobacillus were more abundant in A.muciniphilapretreated mice.Metabolomic analysis revealed that A.muciniphila altered the gut metabolome,with changes involving pathways such as tyrosine metabolism,alanine/aspartate/glutamate homeostasis,cancer-related carbon flux,and GABAergic synaptic signaling.In conclusion,our findings indicate that A.muciniphila exerts renoprotective effects by modulating the gut-kidney axis,thereby establishing a foundation for future studies to explore the connection between gut microbiota and AKI.
基金supported and funded by the National Key Research and Development Program of China(2023YFD1300801)the Agricultural Science and Technology Innovation Program in Chinese Academy of Agricultural Sciences(ASTIP-IAS-08)。
文摘Background The decline in reproductive performance of aged hens is mainly attributed to oxidative damage in reproductive organs,hepatic lipid metabolism disorders,and intestinal microbiota dysbiosis.Glycyrrhizin(GL)has been proven to enhance antioxidant capacity,regulate lipid metabolism and gut microbiota in mammals,but its efficacy in hens remains unclear.Hence,this study aimed to investigate whether dietary GL supplementation improves reproductive performance in hens during the late laying stage by modulating intestinal microbiota composition,hepatic lipid metabolism and ovarian antioxidant status.Results Dietary supplementation with 100 mg/kg GL significantly improved the egg production rate,egg quality,and hatching rate in aged breeder hens(P<0.05).GL supplementation also increased the serum levels of HDLC,TP and ALB,and enhanced the antioxidant capacity in both serum and ovary(P<0.05).In addition,dietary GL elevated the serum progesterone(P4)levels by enhancing the transcription level of steroid synthesis key enzymes(CYP11A1 and 3β-HSD)in the ovary(P<0.05).Dietary GL also promoted the synthesis and transport of vitellogenin(VTG)by upregulating the VTG-Ⅱ(P<0.05)and APOV1(P=0.077)expression levels in the liver,thereby increasing the number of grade follicles and small yellow follicles.Moreover,dietary GL enhanced hepatic fatty acidβ-oxidation by upregulating PPARαand CPT-I(P<0.05),and downregulating ACC expression levels(P<0.05).In agreement,liver metabolomics analysis revealed that dietary GL supplementation significantly altered hepatic metabolism,with 389 differentially identified metabolites(P<0.05).The key metabolites(e.g.,taurocholic acid,tauroursodeoxycholic acid,nicotinuric acid,glycodeoxycholic acid(hydrate))were identified,and they were mainly functionally enriched in betaalanine metabolism nicotinate,taurine and hypotaurine metabolism(P<0.05).Finally,16S rRNA gene sequencing revealed that dietary GL reversed age-induced changes in gut microbiota composition,characterized by a significant increase in Lactobacillus abundance and a decrease in Bacteroides(P<0.05).Conclusions These results collectively demonstrate that dietary supplementation with 100 mg/kg GL improved reproductive performance by reversing age-induced changes in gut microbiota,enhancing hepatic vitellogenin synthesis,and ameliorating ovarian function in aged breeder hens.This study suggests that dietary GL is a potential strategy to improve reproductive performance in broiler breeder hens during the late laying period.
基金supported by the Key Special Projects of the Ministry of Science and Technology(SQ2020YFF0404523)the North Anhui Soybean Advantageous Characteristic Industry Cluster Project(2023CYJQ013)+2 种基金the National Natural Science Foundation of China(32172162)the Key Genetic Technologies Research and Development Program of Hefei(2021GJ075)the Young Talents Program of Anhui Academy of Agricultural Science(QNYC-202122).
文摘Okara is produced in large quantities annually in China,but much of it is discarded due to its high content of indigestible dietary fiber(DF),contributing to significant environmental challenges.Recognizing the underexplored medicinal potential of DF,we developed an efficient fermentation method to enhance the bioavailability of okara fiber.In this study,Pediococcus acidilactici IFJ-1,which has strong enzymatic production capabilities and beneficial effects on gastrointestinal flora modulation,was selected to ferment okara.Results showed decreases in viscosity and particle size,optimized surface structure,improved thermal stability and hydration properties,and a significant increase in soluble DF content from 1.85%to 3.91%.To evaluate the physiological effects,hyperlipidemic mouse models were established and subjected to dietary interventions utilizing okara and fermented okara to measure changes in physicochemical parameters,gut microbiota composition,and lipid metabolism.The dietary intervention was effective,particularly in the fermented okara group,showing a 7.3%weight loss,improved blood lipids(triglycerides:‒39.8%,total cholesterol:‒12.8%,low-density lipoprotein cholesterol:‒34.2%,high-density lipoprotein cholesterol:+26.2%),and a 22.2%lower liver index.Gut microbiota analysis revealed that fermented okara positively modulated the microbial community by increasing the abundance of beneficial bacteria(e.g.,Bacteroidota)and reducing the abundance of obesity-associated bacteria(e.g.,Bacillota).Lipid metabolism profiling further demonstrated that fermented okara downregulated harmful lipids(e.g.,(O-acyl)-ω-hydroxy fatty acids,ceramides,and diacylglycerols)while upregulating beneficial phospholipids(e.g.,phosphatidylinositol,phosphatidylserine,phosphatidylethanolamine,lysophosphatidylinositol and lysophosphatidic acid).This study highlights a novel approach for enhancing DF utilization through fermentation,providing valuable insights into strategies for preventing obesity and metabolic diseases.
基金supported by the National Natural Science Foundation of China(Grant No.82500432)the Heilongjiang Provincial Health Commission Scientific Research Project(Grant No.20240303010111).
文摘Background Recent studies have suggested a potential role of the oral microbiome in the development of cardiovascular diseases.This study aims to investigate the association between oral microbiota and cardiovascular disease risk,including atrial fibrillation,myocardial infarction,chronic heart failure,and hypertension.Methods We analyzed GWAS data from East Asian populations'oral microbiome,involving 2,017 tongue and 1,915 saliva samples from 2,984 individuals with whole-genome sequencing.Additionally,we sourced cardiovascular disease GWAS data from NBDC,including atrial fibrillation(8,180 cases,28,621 controls),myocardial infarction(14,992 cases,146,214 controls),chronic heart failure(10,540 cases,168,186 controls),and systolic blood pressure(145,505 individuals).Results Several oral microbiota taxa were found to be significantly associated with cardiovascular disease outcomes.Specific microbiota,such as Centipeda,Corynebacterium,and Pseudomonas E,were negatively correlated with heart failure.In contrast,taxa like Neisseria D and Actinomyces were associated with an increased risk of atrial fibrillation and myocardial infarction.Additionally,certain oral microbiota showed correlations with changes in blood pressure,highlighting their potential role in hypertension.Conclusion Our findings suggest that the oral microbiota may influence the development and progression of cardiovascular diseases,providing new insights into the potential impact of oral health on cardiovascular risk.
基金The National Natural Science Foundation of China(32302759,32372924)the CAST Youth Talent Support Project-Special Program for Doctoral Students(156-O-230-0000375-5)。
文摘Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.
基金Financial support from the National Natural Science Foundation of China(32502106)One health Interdisciplinary Research Project,Institute of One Health Science,Ningbo University(NBUOH202502)the Ningbo Top Talent Project(215-432094250).
文摘The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.
基金funding from the European Union -NextGenerationEU through the Italian Ministry of University and Research under PRIN PNRR REG D.R.1718-2022– Project number PRJ-1575 INDICA。
文摘Indicaxanthin is a betalain that is abundant in Opuntia ficus-indica orange fruit and has antioxidative and anti-inflammatory effects. Nevertheless, very little is known about the neuroprotective potential of indicaxanthin. This study investigated the impact of indicaxanthin on neuronal damage and gut microbiota dysbiosis induced by a high-fat diet in mice. The mice were divided into three groups according to different diets: the negative control group was fed a standard diet;the high-fat diet group was fed a high-fat diet;and the high-fat diet + indicaxanthin group was fed a high-fat diet and received indicaxanthin orally(0.86 mg/kg per day) for 4 weeks. Brain apoptosis, redox status, inflammation, and the gut microbiota composition were compared among the different animal groups. The results demonstrated that indicaxanthin treatment reduced neuronal apoptosis by downregulating the expression of proapoptotic genes and increasing the expression of antiapoptotic genes. Indicaxanthin also markedly decreased the expression of neuroinflammatory proteins and genes and inhibited high-fat diet–induced neuronal oxidative stress by reducing reactive oxygen and nitrogen species, malondialdehyde, and nitric oxide levels. In addition, indicaxanthin treatment improved the microflora composition by increasing the abundance of healthy bacterial genera, known as producers of short-chain fatty acids(Lachnospiraceae, Alloprovetella, and Lactobacillus), and by reducing bacteria related to unhealthy profiles(Blautia, Faecalibaculum, Romboutsia and Bilophila). In conclusion, indicaxanthin has a positive effect on high-fat diet–induced neuronal damage and on the gut microbiota composition in obese mice.
基金provided by the National Natural Sciences Foundation of China (82270979)High-Level Hospital Construction Project (0224C001,0224C050)Cultivation Program for Reserve Talents for Academic Leaders (2023A208) of Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University。
文摘Epidemiological studies have highlighted an association between periodontitis and osteoporosis.However,the mechanism underlining this association remains unclear.Here,we revealed significant differences in the salivary microbiota between periodontally healthy individuals and periodontitis patients,with periodontitis patients exhibiting increased salivary microbiota diversity and an elevated abundance of pathogenic bacteria.Using an ovariectomized(OVX) mouse model,we demonstrated that the salivary microbiota from periodontitis patients exacerbated bone destruction by modulating the gut microbiota.Metabolomic analysis revealed that the periodontitis-associated salivary microbiota suppressed tryptophan metabolism.The tryptophan metabolite indole-3-lactic acid(ILA) directly inhibited osteoclast formation and differentiation.In OVX mice treated with periodontitis salivary microbiota,supplementation with ILA effectively suppressed osteoclastogenesis and alleviated the detrimental effects of periodontitis-associated salivary microbiota on systemic bones.In summary,our data demonstrate that periodontitis can affect systemic bone metabolism via the oral-gut axis and that ILA supplementation serves as a potential therapeutic option to mitigate these adverse effects.
基金Supported by the Guangdong Provincial Natural Science Foundation(No.2022A1515010783)the Sustainable Development Program of Shenzhen Science and Technology Major Program(No.KCXFZ20240903093925033)+4 种基金the Guangdong Provincial Special Project in Science and Technology(No.2021A05240)the Special Project in Key Fields of Guangdong Provincial Higher Education Institutions(No.2021ZDZX2064)the Basic Research Project of Shenzhen Science and Technology Innovation Commission(No.JCYJ20220530162014032)the Zhanjiang Marine Youth Talent Innovation Project(No.2022E05010)the Program for Scientific Research Start-up Funds of Guangdong Ocean University(Nos.R18008,060302042201)。
文摘Alzheimer’s disease(AD)is a complex neurodegenerative disorder associated with changes in inflammation,oxidative stress,and gut microbiota composition.Butyrolactone Ⅰ(BTL-Ⅰ),a fungal metabolite,has shown anti-inflammatory,microbiota regulating,and memory-improving potentials in previous in vitro and AlCl3-induced zebrafish studies.However,its effects of memory-improving and gutbrain axis regulating on Aβ-induced mammalian AD models have not been explored.In this study,intragastric administrated BTL-Ⅰ ameliorated cognitive deficits related to recognition and spatial memory impaired by Aβ_(1-42)intracerebroventricular injection in mice.BTL-Ⅰ maintained gut microbiota balance by increasing the abundance of Blautia,Muribaculaceae,Bacteroides,Akkermansia,etc.,and decreasing CAG-352,Clostridia UCG-014,different Lachnospiraceae groups,etc.,and Firmicutes/Bacteroidota ratio and elevated the levels of short-chain fatty acids.Additionally,it alleviated intestinal oxidative stress,inflammatory responses,and pathological damage.Furthermore,BTL-I reversed Aβ_(1-42)-induced activation of microglia and astrocytes in the hippocampus and inhibited the elevated oxidative stress and proinflammatory cytokines in both plasma and brain.The correlation analysis between the regulated taxa and biomarkers supports the role of gut microbiota in adjusting inflammation,oxidative stress,and memory.In conclusion,BTL-I may serve as a valuable drug lead for treating Alzheimer’s disease by systematically inhibiting microbiota imbalance,inflammation,and oxidative stress along the gut-brain axis.
