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
In recent years,an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system.This communication occurs through the microbiota-...In recent years,an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system.This communication occurs through the microbiota-gut-brain axis.As people age,the composition of the gut microbiota undergoes considerable changes,which are now known to play an important role in the development of many neurodegenerative diseases.This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain.It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation,maintaining gut health,and influencing the development of neurodegenerative diseases such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders,including fecal microbiota transplantation,probiotics,and prebiotics.Many studies show that the gut microbiota affects the brain in several ways.For example,it can produce substances such as short-chain fatty acids and activate inflammatory pathways.Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems.Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism’s health.Microorganisms primarily colonize the gut and are involved in host nutrient metabolism,maintaining the structural integrity of the intestine,preserving the intestinal mucosal barrier,and modulating the immune system.The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis.The composition of the gut flora changes considerably with age,and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging.Recent studies have linked these changes to a variety of age-related neurological disorders,including Alzheimer’s disease,amyotrophic lateral sclerosis,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.Specifically,the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways.In preclinical studies,targeted modulation of the gut microbiota,through methods such as fecal microbiota transplantation,probiotics,and prebiotics,has demonstrated potential in improving host behavioral outcomes.Therefore,gut microbiota-based treatments offer new hope for the treatment of nervous system diseases.However,due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies,researchers need to carefully assess their safety and efficacy before widespread clinical application.展开更多
Background Perilla frutescens seeds(PFS)are gaining recognition as a natural alternative to antibiotics in livestock,supporting sustainable farming and animal health.However,the underlying molecular mechanisms through...Background Perilla frutescens seeds(PFS)are gaining recognition as a natural alternative to antibiotics in livestock,supporting sustainable farming and animal health.However,the underlying molecular mechanisms through which PFS influence host immune function and antioxidant capacity,especially via the gut-liver-muscle axis,remain largely unknown.This study employed an integrative multi-omics approach to elucidate how PFS supplementation modulates the microbiota-gut-liver-muscle axis and enhances immune and antioxidant functions in lambs.Results PFS supplementation markedly improved immune and antioxidant profiles,demonstrated by elevated serum levels of IL-10,IgM,IgG,GSH-PX,and SOD,and reductions in IL-1β,TNF-α,and MDA.Microbial analysis revealed elevated abundances of ruminal and intestinal taxa commonly associated with gut homeostasis and metabolic health(Christensenellaceae_R-7_group)and reduced levels of species with pathogenic or pro-inflammatory potential(Bacillus cereus and Clostridioides)in the ileum.Transcriptomic and metabolomic profiling of liver tissue indicated modulation of key inflammatory and bile acid signaling pathways,including the downregulation of TLR4,NLRP3,ATF3,CYP2J2,and LXR-α.PFS also increased hepatic concentrations of anti-inflammatory metabolites such as chlorquinaldol and indole-3-carboxaldehyde,while reducing levels of LysoPC(20:4)and phosphatidic acid.Correlation and mediation analyses revealed strong interconnections among gut microbiota,hepatic gene expression,lipid metabolites in liver and muscle,and systemic immune-antioxidant markers.Conclusion These findings highlight the microbiota-gut-liver-muscle axis as a central mechanism through which PFS enhances immune function and antioxidant capacity in lambs.PFS supplementation represents a promising nutritional strategy to improve healthy lamb production,supporting the development of antibiotic-free and sustainable livestock systems.展开更多
Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild fem...Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild females,causing generation-to-generation suppression.Medflies are colonized by microorganisms,primarily the Enterobacteriaceae,with the genera Klebsiella and Enterobacter being the most common.Such microbiota contributes to host fitness.During the SIT,diet with antibiotics and irradiation for sterility of adults alter microbiota.We aimed to determine the role of Medfly microbiota on resistance to abiotic stress conditions,evaluating its function under:(i)starvation,(ii)elevated temperatures,and(iii)dry environments.These conditions simulate challenges Medfly may encounter after release,which differ from controlled rearing environments.We compared adult survival between symbiotic and aposymbiotic individuals,under starvation,two thermal regimes(25 and 30℃)or two humidity regimes(20%-25%and 80%-90%R.H.).Aposymbiotic individuals were obtained after providing them with water containing a mixture of antibiotics and methylparaben.Treatment with antimicrobials effectively reduced the gut microbiota.While starvation had no significant effect on survival,a higher proportion of aposymbiotic individuals died earlier at 30℃ and under dry humidity,with the effect being more pronounced after 48 h.Our results suggest that microbiota plays a role in adaptation of Medfly under environmental stress.We report for the presence of a culturable yeast in the digestive tract of C.capitata,Zygosaccharomyces rouxii.Providing a probiotic adult diet with bacteria and Z.rouxii prior to release could improve SIT outcomes under adverse conditions.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
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
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
Background Post-weaning diarrhea(PWD)in piglets,primarily caused by enterotoxigenic Escherichia coli(ETEC)K88(F4)infection,presents a major challenge in swine production.This study aimed to isolate bacteriophages(phag...Background Post-weaning diarrhea(PWD)in piglets,primarily caused by enterotoxigenic Escherichia coli(ETEC)K88(F4)infection,presents a major challenge in swine production.This study aimed to isolate bacteriophages(phages)specific to ETEC K88,utilizing ETEC K88 as the host strain,and to assess the efficacy of dietary supplementation with the isolated phages in weaned piglets over a two-week period using an ETEC K88 challenge model in a pilot study.Results Three ETEC K88-specific phages(EC-P1,EC-P2,and EC-P3)were isolated and identified as tailed phages.These phages displayed a short latency period,broad acid–base stability,and thermal stability,effectively inhibiting ETEC K88 growth and disrupting ETEC K88 biofilms in vitro.Lyophilized phage powder was prepared and supplemented at 400,600 or 800 mg/kg in the diets.Compared to the ETEC K88 group,piglets in the ETEC K88+600 or 800 mg/kg phages group exhibited markedly lower diarrhea scores and rectal temperatures at 12,24,and 48 h post-infection.Supplementation with 600 mg/kg phages enhanced intestinal integrity of ETEC K88-infected piglets,as evidenced by an increased jejunal villus height and villus height-to-crypt depth ratio,reduced serum diamine oxidase and D-lactate levels,and upregulated jejunal ZO-1 protein expression.Concomitantly,systemic and jejunal inflammatory responses were attenuated by supplementation with 600 mg/kg of phages,as evidenced by decreased serum LPS,IL-1β,IL-10 and TNF-α levels,down-regulated jejunal IL-1β and IL-6 mRNA expression,and suppressed NF-κB signalling(downregulated p-IκBα/IκBα and p-p65/p65 ratios).Supplementation with 600 mg/kg phages also shifted the faecal microbiota toward eubiosis,increasing the Shannon index,decreasing Proteobacteria and Enterobacteriaceae abundances,and elevating beneficial taxa(Patescibacteria,Muribaculaceae,and Subdoligranulum).Correlation analysis further revealed that Proteobacteria and Enterobacteriaceae abundances were positively associated with diarrhoea characteristics,whereas Muribaculaceae showed a negative correlation.Conclusions Three ETEC K88-targeting phages were successfully isolated,characterized,and prepared as lyophilized phage powder for dietary supplementation.Dietary supplementation with 600 mg/kg of lyophilized phage powder alleviated PWD in piglets by modulating gut microbiota and inflammatory responses.展开更多
Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particul...Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particularly those associated with antioxidant defense,intestinal development and host-microbiota interactions.Method A total of 1001-day-old Pekin ducklings were used in this study with 50 DHAV-3 susceptible and resistant ducks,respectively.Samples were collected at 7 days post-hatching(D7),D21 and D42,10 birds per group.We compared DHAV-3 resistant and susceptible ducks during early development with respect to immune organ indices,antioxidant capacity,intestinal morphology,barrier-related gene expression and cecal microbiota.Result Resistant ducks exhibited higher spleen indices and stronger antioxidant capacity,characterized by increased superoxide dismutase,reduced glutathione,and total antioxidant capacity,along with lower malondialdehyde levels at D7 and D21.In contrast,susceptible ducks showed compensatory thymus hypertrophy and delayed development of antioxidant defense and intestinal maturation.Ileal morphology revealed greater villus height and width with more regular arrangement in resistant ducks at D7,whereas these differences diminished at D21 and D42.Gene expression analysis demonstrated higher early expression of the tight junction proteins CLDN1 and CLDN3 in resistant ducks,while susceptible ducks displayed elevated MUC2 and OCLN,suggesting stress induced compensatory responses.Cecal microbiota analysis revealed distinct colonization patterns in early development.Resistant ducks were enriched with Firmicutes and beneficial genera such as Enterococcus and Lactobacillus,whereas susceptible ducks harbored higher abundances of Bacteroidota and potentially opportunistic taxa.Microbial diversity increased with age in both groups,but resistant ducks displayed more orderly succession and enrichment of SCFA producing genera,including Subdoligranulum and Phascolarctobacterium,which positively correlated with plasma antioxidant indices.Conclusion DHAV-3 resistant ducks exhibit early advantages in antioxidant defense,intestinal barrier development and colonization by beneficial microbiota,which collectively contribute to enhanced disease resistance.These findings highlight the synergistic roles of host physiology and gut microbiota in shaping resistance.In the future,integrating genomic selection with microbiota modulation and antioxidant interventions may accelerate the breeding of highly resistant duck lines and provide scientific evidence and practical strategies for controlling duck viral hepatitis.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
OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation...OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.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
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
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
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supported by the National Natural Science Foundation of China,No.32200782(to ZL)the Science and Technology Development Plan Project of Jilin Province,No.20240404014ZP(to ZL).
文摘In recent years,an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system.This communication occurs through the microbiota-gut-brain axis.As people age,the composition of the gut microbiota undergoes considerable changes,which are now known to play an important role in the development of many neurodegenerative diseases.This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain.It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation,maintaining gut health,and influencing the development of neurodegenerative diseases such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders,including fecal microbiota transplantation,probiotics,and prebiotics.Many studies show that the gut microbiota affects the brain in several ways.For example,it can produce substances such as short-chain fatty acids and activate inflammatory pathways.Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems.Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism’s health.Microorganisms primarily colonize the gut and are involved in host nutrient metabolism,maintaining the structural integrity of the intestine,preserving the intestinal mucosal barrier,and modulating the immune system.The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis.The composition of the gut flora changes considerably with age,and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging.Recent studies have linked these changes to a variety of age-related neurological disorders,including Alzheimer’s disease,amyotrophic lateral sclerosis,Parkinson’s disease,multiple sclerosis,and Huntington’s disease.Specifically,the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways.In preclinical studies,targeted modulation of the gut microbiota,through methods such as fecal microbiota transplantation,probiotics,and prebiotics,has demonstrated potential in improving host behavioral outcomes.Therefore,gut microbiota-based treatments offer new hope for the treatment of nervous system diseases.However,due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies,researchers need to carefully assess their safety and efficacy before widespread clinical application.
基金supported by the Central Government-Guided Local Science and Technology Development Fund Project(2025ZY0108)Bayannaoer Research Institute Young Scientist Project(2024BYNECAU002)+1 种基金Hainan Provincial Natural Science Foundation of China(324QN289)the China Agriculture Research System(CARS-38)。
文摘Background Perilla frutescens seeds(PFS)are gaining recognition as a natural alternative to antibiotics in livestock,supporting sustainable farming and animal health.However,the underlying molecular mechanisms through which PFS influence host immune function and antioxidant capacity,especially via the gut-liver-muscle axis,remain largely unknown.This study employed an integrative multi-omics approach to elucidate how PFS supplementation modulates the microbiota-gut-liver-muscle axis and enhances immune and antioxidant functions in lambs.Results PFS supplementation markedly improved immune and antioxidant profiles,demonstrated by elevated serum levels of IL-10,IgM,IgG,GSH-PX,and SOD,and reductions in IL-1β,TNF-α,and MDA.Microbial analysis revealed elevated abundances of ruminal and intestinal taxa commonly associated with gut homeostasis and metabolic health(Christensenellaceae_R-7_group)and reduced levels of species with pathogenic or pro-inflammatory potential(Bacillus cereus and Clostridioides)in the ileum.Transcriptomic and metabolomic profiling of liver tissue indicated modulation of key inflammatory and bile acid signaling pathways,including the downregulation of TLR4,NLRP3,ATF3,CYP2J2,and LXR-α.PFS also increased hepatic concentrations of anti-inflammatory metabolites such as chlorquinaldol and indole-3-carboxaldehyde,while reducing levels of LysoPC(20:4)and phosphatidic acid.Correlation and mediation analyses revealed strong interconnections among gut microbiota,hepatic gene expression,lipid metabolites in liver and muscle,and systemic immune-antioxidant markers.Conclusion These findings highlight the microbiota-gut-liver-muscle axis as a central mechanism through which PFS enhances immune function and antioxidant capacity in lambs.PFS supplementation represents a promising nutritional strategy to improve healthy lamb production,supporting the development of antibiotic-free and sustainable livestock systems.
基金Fund for Scientific and Technological Research of Argentina(FONCyT PICT 2018 number 03521).
文摘Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild females,causing generation-to-generation suppression.Medflies are colonized by microorganisms,primarily the Enterobacteriaceae,with the genera Klebsiella and Enterobacter being the most common.Such microbiota contributes to host fitness.During the SIT,diet with antibiotics and irradiation for sterility of adults alter microbiota.We aimed to determine the role of Medfly microbiota on resistance to abiotic stress conditions,evaluating its function under:(i)starvation,(ii)elevated temperatures,and(iii)dry environments.These conditions simulate challenges Medfly may encounter after release,which differ from controlled rearing environments.We compared adult survival between symbiotic and aposymbiotic individuals,under starvation,two thermal regimes(25 and 30℃)or two humidity regimes(20%-25%and 80%-90%R.H.).Aposymbiotic individuals were obtained after providing them with water containing a mixture of antibiotics and methylparaben.Treatment with antimicrobials effectively reduced the gut microbiota.While starvation had no significant effect on survival,a higher proportion of aposymbiotic individuals died earlier at 30℃ and under dry humidity,with the effect being more pronounced after 48 h.Our results suggest that microbiota plays a role in adaptation of Medfly under environmental stress.We report for the presence of a culturable yeast in the digestive tract of C.capitata,Zygosaccharomyces rouxii.Providing a probiotic adult diet with bacteria and Z.rouxii prior to release could improve SIT outcomes under adverse conditions.
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 National Natural Science Foundation of China(No.32472940 and No.32160806)the Jiangxi Provincial Cultivation Program for Academic and Technical Leaders of Major Subjects(No.20213BCJ22005)+1 种基金the Key Research and Development Program of Jiangxi Province(No.20223BBF61018)the Key Research and Development Program of Jiangxi Province(No.20224BBF61029),China。
文摘Background Post-weaning diarrhea(PWD)in piglets,primarily caused by enterotoxigenic Escherichia coli(ETEC)K88(F4)infection,presents a major challenge in swine production.This study aimed to isolate bacteriophages(phages)specific to ETEC K88,utilizing ETEC K88 as the host strain,and to assess the efficacy of dietary supplementation with the isolated phages in weaned piglets over a two-week period using an ETEC K88 challenge model in a pilot study.Results Three ETEC K88-specific phages(EC-P1,EC-P2,and EC-P3)were isolated and identified as tailed phages.These phages displayed a short latency period,broad acid–base stability,and thermal stability,effectively inhibiting ETEC K88 growth and disrupting ETEC K88 biofilms in vitro.Lyophilized phage powder was prepared and supplemented at 400,600 or 800 mg/kg in the diets.Compared to the ETEC K88 group,piglets in the ETEC K88+600 or 800 mg/kg phages group exhibited markedly lower diarrhea scores and rectal temperatures at 12,24,and 48 h post-infection.Supplementation with 600 mg/kg phages enhanced intestinal integrity of ETEC K88-infected piglets,as evidenced by an increased jejunal villus height and villus height-to-crypt depth ratio,reduced serum diamine oxidase and D-lactate levels,and upregulated jejunal ZO-1 protein expression.Concomitantly,systemic and jejunal inflammatory responses were attenuated by supplementation with 600 mg/kg of phages,as evidenced by decreased serum LPS,IL-1β,IL-10 and TNF-α levels,down-regulated jejunal IL-1β and IL-6 mRNA expression,and suppressed NF-κB signalling(downregulated p-IκBα/IκBα and p-p65/p65 ratios).Supplementation with 600 mg/kg phages also shifted the faecal microbiota toward eubiosis,increasing the Shannon index,decreasing Proteobacteria and Enterobacteriaceae abundances,and elevating beneficial taxa(Patescibacteria,Muribaculaceae,and Subdoligranulum).Correlation analysis further revealed that Proteobacteria and Enterobacteriaceae abundances were positively associated with diarrhoea characteristics,whereas Muribaculaceae showed a negative correlation.Conclusions Three ETEC K88-targeting phages were successfully isolated,characterized,and prepared as lyophilized phage powder for dietary supplementation.Dietary supplementation with 600 mg/kg of lyophilized phage powder alleviated PWD in piglets by modulating gut microbiota and inflammatory responses.
基金supported by the National Key R&D Program of China(2022YFD1301800)grants from the National Natural Science Foundation of China(grant number 32502899)+1 种基金China Agriculture Research System of MOF and MARA(CARS-42-10)the Agricultural Science and Technology Innovation Program of CAAS(CAAS-ASTIP-2023-IFR-13)。
文摘Background Selective breeding for disease resistance is an effective strategy to control duck hepatitis A virus type 3(DHAV-3)in waterfowl.However,the mechanism underlying resistance remains poorly understood,particularly those associated with antioxidant defense,intestinal development and host-microbiota interactions.Method A total of 1001-day-old Pekin ducklings were used in this study with 50 DHAV-3 susceptible and resistant ducks,respectively.Samples were collected at 7 days post-hatching(D7),D21 and D42,10 birds per group.We compared DHAV-3 resistant and susceptible ducks during early development with respect to immune organ indices,antioxidant capacity,intestinal morphology,barrier-related gene expression and cecal microbiota.Result Resistant ducks exhibited higher spleen indices and stronger antioxidant capacity,characterized by increased superoxide dismutase,reduced glutathione,and total antioxidant capacity,along with lower malondialdehyde levels at D7 and D21.In contrast,susceptible ducks showed compensatory thymus hypertrophy and delayed development of antioxidant defense and intestinal maturation.Ileal morphology revealed greater villus height and width with more regular arrangement in resistant ducks at D7,whereas these differences diminished at D21 and D42.Gene expression analysis demonstrated higher early expression of the tight junction proteins CLDN1 and CLDN3 in resistant ducks,while susceptible ducks displayed elevated MUC2 and OCLN,suggesting stress induced compensatory responses.Cecal microbiota analysis revealed distinct colonization patterns in early development.Resistant ducks were enriched with Firmicutes and beneficial genera such as Enterococcus and Lactobacillus,whereas susceptible ducks harbored higher abundances of Bacteroidota and potentially opportunistic taxa.Microbial diversity increased with age in both groups,but resistant ducks displayed more orderly succession and enrichment of SCFA producing genera,including Subdoligranulum and Phascolarctobacterium,which positively correlated with plasma antioxidant indices.Conclusion DHAV-3 resistant ducks exhibit early advantages in antioxidant defense,intestinal barrier development and colonization by beneficial microbiota,which collectively contribute to enhanced disease resistance.These findings highlight the synergistic roles of host physiology and gut microbiota in shaping resistance.In the future,integrating genomic selection with microbiota modulation and antioxidant interventions may accelerate the breeding of highly resistant duck lines and provide scientific evidence and practical strategies for controlling duck viral hepatitis.
基金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'Modernization Research of Traditional Chinese Medicine':Cardiovascular Event Chain(Metabolic Syndrome,Atherosclerosis,Myocardial Infarction,Arrhythmia,Heart Failure)(No.2017YFC700500)the Key R&D Program of Hebei:Traditional Chinese Medicine Innovation Project:Clinical Research on the Treatment of Diabetes Foot with Collateral Drugs and the Mechanism of Its Influence on Collateral Vessel Reconstruction(No.223777155D)+1 种基金the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Jinlida Granules in Treating Intestinal Dysfunction of diabetes and Its Effect on Short Chain Fatty Acids(No.2023179)the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Tongluo Therapy for Diabetes Foot and Its Influence on Microcirculation(No.2018200)。
文摘OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.
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 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.
