Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We ex...Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We explored the effects of the combined pollution with PMB and arsenic(As)on the microbial composition of the soil and in the earthworm gut,as well as the spread and transmission of antibiotic resistance genes(ARGs).The results showed that,compared with As alone,the combined addition of PMB and As could significantly increase the bioaccumulation factor and toxicity of As in earthworm tissues by 12.1%and 16.0%,respectively.PMB treatment could significantly increase the abundance of Actinobacteria in the earthworm gut(from 35.6%to 45.2%),and As stress could significantly increase the abundance of Proteobacteria(from 19.8%to 56.9%).PMB and As stress both could significantly increase the abundance of ARGs and mobile genetic elements(MGEs),which were positively correlated,indicating that ARGs might be horizontally transferred.The inactivation of antibiotics was the main resistance mechanism that microbes use to resist PMB and As stress.Network analysis showed that PMB and As might have antagonistic effects through competition with multi-drug resistant ARGs.The combined pollution by PMB and As significantly promoted the relative abundance of microbes carrying multi-drug resistant ARGs and MGEs,thereby increasing the risk of transmission of ARGs.This research advances the understanding of the interaction mechanism between antibiotics and heavy metals and provides new theoretical guidance for the environmental risk assessment and combined pollution management.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
Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented...In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
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
Background Nicotinamide riboside(NR)supplementation has been demonstrated efficacy in enhancing female reproductive outcomes,but its regulatory role in sow performance and gut microbiome remains undefined.This study s...Background Nicotinamide riboside(NR)supplementation has been demonstrated efficacy in enhancing female reproductive outcomes,but its regulatory role in sow performance and gut microbiome remains undefined.This study systematically evaluated the impacts of dietary NR supplementation during late gestation and lactation on sow performance and gut microbiome remodeling.A total of 280 sows were randomized assigned to one of four groups:a control group fed basal diet or one of three groups receiving NR-supplemented diets(2,4,or 8 g/d;n=70/group).Sow reproductive performance,blood metabolic parameters,milk metabolome,and fecal 16S rRNA sequencing were measured.Results Maternal NR supplementation linearly shortened farrowing duration(P<0.01)and tended to decrease the incidence of intrauterine growth restriction and the number of late gestation mummies(P<0.1),while concurrently increasing the within-litter uniformity(P=0.1).Litter weaning weight and average daily gain increased quadratically with NR dosage(P<0.05).NR supplementation orchestrated plasma metabolite regulation(triglycerides and total cholesterol;P<0.05),enhanced antioxidant biomarkers(T-AOC,GSH-Px,T-SOD;P<0.05),and reduced inflammatory cytokines(TNF-α;P<0.05)across gestation and lactation.Milk yield,colostrum/milk dry matter,crude protein,and crude fat were increased(P<0.05),together with higher levels of NAD^(+)metabolites(NAD^(+),NR,nicotinamide)and beneficial bioactive factors(milk polar lipids,3-aminosalicylic acid,fenugreekine;P<0.05).Gut microbiota analyses at lactation day 14 revealed NR-enriched beneficial taxa(Bifidobacterium,Ruminococcus,Lachnospiraceae,Subdoligranulum,Clostridium butyricum,Succiniclasticum)across sow-offspring dyads,which was associated with the activation of microbial NAD^(+)enzymes(NadR/NAMPT;P<0.05)and enhancement of systemic short-chain fatty acid flux,notably an increase in plasma butyrate acid(P<0.05).Conclusion Maternal supplementation of NR during late gestation and lactation increases sow performance and promotes gut NAD^(+)metabolic-associated microbiome remodeling.These findings propose maternal NR intervention as a novel strategy to enhance mammary lactogenesis and lactation metabolism in swine production,with potential applications for therapeutic strategies for lactation insufficiency.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
Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal micro...Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.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
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
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
Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as...Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as a comprehensive intervention on human health and immune status.This study used a 14-day continuous drinking intervention consisting of 5 beers,namely white beer,India pale ale(IPA),Pilsner,non-alcoholic beer,and premium lager beer.Surprisingly,our findings indicate that consuming white beer has little impact on the gut microbiota and physiological condition of mice,whereas consuming other types of beer leads to an increase in Lactobacillus and a decrease in Lachnospiraceae.In addition,we devised an extended feeding experiment to investigate the comparative safety and health benefits of consuming white beer.The research showed that when mice drank excessive quantities of white beer over 42 days,the intestines of the mice had more Prevotellaceae and the Firmicutes to Bacteroidetes ratio(F/B ratio)had a decline from 1.29 to 0.38.The levels of acetic acid,propionic acid,and isobutyric acid increased from 1.0,0.27,and 0.015 mg/g to 1.28,0.38,and 0.037 mg/g,respectively(P<0.05).There were no significant changes observed in the levels of most measured cytokines in the colon tissue of mice that consumed beer,however,there was an increase in the concentration of the inflammatory factor tumor nesrosis factor-α(TNF-α)from 135.86 pg/mL in the control group to 189.78 pg/mL in the white beer group(P<0.01).These results give us real-world proof that we can use to study how different beers affect the host’s health and satisfaction in future research.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
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
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
Gut-brain communication via the peripheral neural network is vital for regulating local digestive function and systemic physiology.Gut microbiota,which produces a wide array of neuroactive compounds,is a critical modu...Gut-brain communication via the peripheral neural network is vital for regulating local digestive function and systemic physiology.Gut microbiota,which produces a wide array of neuroactive compounds,is a critical modulator in this bidirectional dialog.Perturbations in the gut microbiota have been implicated in neurological disorders such as depression and stress.Distinct from humans and other monogastric animals,ruminants possess a unique,microbially dense gastrointestinal compartment,the rumen,that facilitates the digestion of fibrous plant materials.These ruminal microbes are likely key contributors to rumen-brain crosstalk.Unlike certain microbe-derived neuroactive compounds produced in the hindgut that are minimally absorbed and primarily excreted in feces,those generated in rumen can reach the small intestine,where they are largely absorbed and affect central nervous system through systemic regulation in addition to the vagal pathway.Notably,emerging evidence suggests that rumen microbiota dysbiosis under stress is associated with abnormal behavior,altered hormonal and neurotransmitter levels.In this review,we introduce the concept of the rumen-microbiome-brain axis by comparing the anatomical structures and microbial characteristics of the intestine and the rumen,emphasizing the neuroactive potential of rumen microbiome and underlying mechanisms.Advances in this frontier hold tremendous promise to reveal a novel dimension of the gut-microbiome-brain axis,providing transformative opportunities to improve ruminant welfare,productivity,and agricultural sustainability.展开更多
Background As probiotics,Bacillus strains may regulate some physiological functions in animals.This study aimed to evaluate whether dietary supplementation with a Bacillus-based probiotic could alleviate gut damage in...Background As probiotics,Bacillus strains may regulate some physiological functions in animals.This study aimed to evaluate whether dietary supplementation with a Bacillus-based probiotic could alleviate gut damage induced by rotavirus(RV)infection in piglets.Twenty-four piglets were randomly assigned into 2 groups fed with the basal diet(n=16)and the diet containing 10^(9) colony-forming unit Bacillus spores/kg(n=8).On d 8,8 piglets fed with the diet supplemented with Bacillus-based probiotic and 8 piglets fed with basal diet were orally infused with RV,while the residue piglets had oral gavage of sterile essential medium.The trial duration was 12 d.Results RV challenge induced diarrhea,significantly destroyed the morphology of jejunal mucosa(P<0.05),significantly increased RV-antibody and RV non-structural protein 4 of jejunal mucosa(P<0.05),significantly impaired antioxidant capacity(including malondialdehyde level,total antioxidant capacity and catalase activity),immunity(such as interleukin 2,interleukin 4 and secreted immunoglobulin A levels),mucins and the m RNA expression of tightjunction-related(such as Zonula occludens 1,occludin)and apoptotic-related(including B-cell lymphoma/leukaemia-2-associated X protein,B cell lymphoma/leukaemia-2,cysteinyl aspartate specific proteinases)genes of jejunal mucosa(P<0.05),and,to some extents,affected the bacteria community structure and abundance of ileal digesta in piglets.However,Bacillus-based probiotic administration could significantly attenuate the negative effects of RV infection on gut health of piglets(P<0.05).Conclusions These findings suggested that supplementing Bacillus-based probiotic in the diet could decrease diarrhea rate,and improve gut health in weaned piglets,which was associated with regulating intestinal antioxidant capacity,apoptosis,and microbiota.展开更多
Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Lite...Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.展开更多
基金supported by the National Natural Science Foundation of China(Nos.41991332 and 41977323).
文摘Polymyxin B(PMB)is considered as the last line of antibiotic defense available to humans.The environmental effects of the combined pollution with PMB and heavy metals and their interaction mechanisms are unclear.We explored the effects of the combined pollution with PMB and arsenic(As)on the microbial composition of the soil and in the earthworm gut,as well as the spread and transmission of antibiotic resistance genes(ARGs).The results showed that,compared with As alone,the combined addition of PMB and As could significantly increase the bioaccumulation factor and toxicity of As in earthworm tissues by 12.1%and 16.0%,respectively.PMB treatment could significantly increase the abundance of Actinobacteria in the earthworm gut(from 35.6%to 45.2%),and As stress could significantly increase the abundance of Proteobacteria(from 19.8%to 56.9%).PMB and As stress both could significantly increase the abundance of ARGs and mobile genetic elements(MGEs),which were positively correlated,indicating that ARGs might be horizontally transferred.The inactivation of antibiotics was the main resistance mechanism that microbes use to resist PMB and As stress.Network analysis showed that PMB and As might have antagonistic effects through competition with multi-drug resistant ARGs.The combined pollution by PMB and As significantly promoted the relative abundance of microbes carrying multi-drug resistant ARGs and MGEs,thereby increasing the risk of transmission of ARGs.This research advances the understanding of the interaction mechanism between antibiotics and heavy metals and provides new theoretical guidance for the environmental risk assessment and combined pollution management.
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 the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金Supported by the National Key Research and Development Program of Traditional Chinese Medicine Modernization Project,China(No.2023YFC3504000)the Science and Technology Development Project of Jilin Province,China(No.20240404043ZP)the Science and Technology Innovation Cooperation Project of Changchun Science and Technology Bureau and Chinese Academy of Sciences,China(No.23SH14)。
文摘In this study,a novel polysaccharide GPA-G 2-H was derived from ginseng.Furthermore,the coherent study of its structural characteristics,fermented characteristics in vitro,as well as antioxidant mechanism of fermented product FGPA-G 2-H on Aβ25-35-induced PC 12 cells were explored.The structure of GPA-G 2-H was determined by means of zeta potential analysis,FTIR,HPLC,XRD,GC-MS and NMR.The backbone of GPA-G 2-H was mainly composed of→4)-α-D-Glcp-(1→with branches substituted at O-3.Notably,GPA-G 2-H was degraded by intestinal microbiota in vitro with total sugar content and pH value decreasing,and short-chain fatty acids(SCFAs)increasing.Moreover,GPA-G 2-H significantly promoted the proliferation of Lactobacillus,Muribaculaceae and Weissella,thereby making positive alterations in intestinal microbiota composition.Additionally,FGPA-G 2-H activated the Nrf 2/HO-1 signaling pathway,enhanced HO-1,NQO 1,SOD and GSH-Px,while inhabited Keap 1,MDA and LDH,which alleviated Aβ-induced oxidative stress in PC 12 cells.These provide a solid theoretical basis for the further development of ginseng polysaccharides as functional food and antioxidant drugs.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
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jointly supported by the National Key R&D Program of China(2023YFD1300804)the National Natural Science Foundation of China(32472948)the earmarked fund for China Agriculture Research System(CARS-35)。
文摘Background Nicotinamide riboside(NR)supplementation has been demonstrated efficacy in enhancing female reproductive outcomes,but its regulatory role in sow performance and gut microbiome remains undefined.This study systematically evaluated the impacts of dietary NR supplementation during late gestation and lactation on sow performance and gut microbiome remodeling.A total of 280 sows were randomized assigned to one of four groups:a control group fed basal diet or one of three groups receiving NR-supplemented diets(2,4,or 8 g/d;n=70/group).Sow reproductive performance,blood metabolic parameters,milk metabolome,and fecal 16S rRNA sequencing were measured.Results Maternal NR supplementation linearly shortened farrowing duration(P<0.01)and tended to decrease the incidence of intrauterine growth restriction and the number of late gestation mummies(P<0.1),while concurrently increasing the within-litter uniformity(P=0.1).Litter weaning weight and average daily gain increased quadratically with NR dosage(P<0.05).NR supplementation orchestrated plasma metabolite regulation(triglycerides and total cholesterol;P<0.05),enhanced antioxidant biomarkers(T-AOC,GSH-Px,T-SOD;P<0.05),and reduced inflammatory cytokines(TNF-α;P<0.05)across gestation and lactation.Milk yield,colostrum/milk dry matter,crude protein,and crude fat were increased(P<0.05),together with higher levels of NAD^(+)metabolites(NAD^(+),NR,nicotinamide)and beneficial bioactive factors(milk polar lipids,3-aminosalicylic acid,fenugreekine;P<0.05).Gut microbiota analyses at lactation day 14 revealed NR-enriched beneficial taxa(Bifidobacterium,Ruminococcus,Lachnospiraceae,Subdoligranulum,Clostridium butyricum,Succiniclasticum)across sow-offspring dyads,which was associated with the activation of microbial NAD^(+)enzymes(NadR/NAMPT;P<0.05)and enhancement of systemic short-chain fatty acid flux,notably an increase in plasma butyrate acid(P<0.05).Conclusion Maternal supplementation of NR during late gestation and lactation increases sow performance and promotes gut NAD^(+)metabolic-associated microbiome remodeling.These findings propose maternal NR intervention as a novel strategy to enhance mammary lactogenesis and lactation metabolism in swine production,with potential applications for therapeutic strategies for lactation insufficiency.
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supported by the National Key R&D Program of China(2023YFD1801100)China National Postdoctoral Program for Innovative Talents(BX20230140)China Postdoctoral Science Foundation(2023M741348)。
文摘Mastitis is one of the most significant diseases affecting the development of the dairy industry and has traditionally been associated with pathogenic infections.However,emerging evidence highlights that ruminal microbial homeostasis also plays a crucial role in the pathogenesis of mastitis.Specifically,cows with mastitis exhibit reduced alpha diversity and altered microbial composition in the rumen.Inducing ruminal dysbiosis through a high-concentrate diet has been shown to trigger mastitis in cows,and transplantation of ruminal microbiota from mastitis-affected cows to recipient mice can induce mastitis in mice.Mechanistically,ruminal dysbiosis increases gastrointestinal inflammation and compromises the integrity of the gastrointestinal barrier,thereby facilitating the translocation of harmful bacterial components,metabolites,and pathobionts into the bloodstream.This disruption impairs blood-milk barrier function,leading to systemic inflammation and the development of mastitis.In this review,we summarize recent advances in understanding how ruminal dysbiosis induces mastitis and explore potential prevention and control strategies targeting the modulation of ruminal microbiota.
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 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financially supported by the National Key R&D Program of China(2022YFA1304103)Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(CXGC2024A04)SKLMT Frontiers&Challenges Project.
文摘Beer is a prominent fermented food product and is regarded as the one of most widely consumed beverage globally.There is a dearth of studies examining the impact of different types of beer with intricate components as a comprehensive intervention on human health and immune status.This study used a 14-day continuous drinking intervention consisting of 5 beers,namely white beer,India pale ale(IPA),Pilsner,non-alcoholic beer,and premium lager beer.Surprisingly,our findings indicate that consuming white beer has little impact on the gut microbiota and physiological condition of mice,whereas consuming other types of beer leads to an increase in Lactobacillus and a decrease in Lachnospiraceae.In addition,we devised an extended feeding experiment to investigate the comparative safety and health benefits of consuming white beer.The research showed that when mice drank excessive quantities of white beer over 42 days,the intestines of the mice had more Prevotellaceae and the Firmicutes to Bacteroidetes ratio(F/B ratio)had a decline from 1.29 to 0.38.The levels of acetic acid,propionic acid,and isobutyric acid increased from 1.0,0.27,and 0.015 mg/g to 1.28,0.38,and 0.037 mg/g,respectively(P<0.05).There were no significant changes observed in the levels of most measured cytokines in the colon tissue of mice that consumed beer,however,there was an increase in the concentration of the inflammatory factor tumor nesrosis factor-α(TNF-α)from 135.86 pg/mL in the control group to 189.78 pg/mL in the white beer group(P<0.01).These results give us real-world proof that we can use to study how different beers affect the host’s health and satisfaction in future research.
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 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 National Institute of Food and Agriculture,U.S.Department of Agriculture,under the award number 2024-67015-42622 to PFMississippi State Agricultural and Forestry Experiment Station(MAFES)Strategic Research Initiative Programsupported by the Mississippi State University College of Agriculture and Life Science/MAFES Undergraduate Research Scholars Program。
文摘Gut-brain communication via the peripheral neural network is vital for regulating local digestive function and systemic physiology.Gut microbiota,which produces a wide array of neuroactive compounds,is a critical modulator in this bidirectional dialog.Perturbations in the gut microbiota have been implicated in neurological disorders such as depression and stress.Distinct from humans and other monogastric animals,ruminants possess a unique,microbially dense gastrointestinal compartment,the rumen,that facilitates the digestion of fibrous plant materials.These ruminal microbes are likely key contributors to rumen-brain crosstalk.Unlike certain microbe-derived neuroactive compounds produced in the hindgut that are minimally absorbed and primarily excreted in feces,those generated in rumen can reach the small intestine,where they are largely absorbed and affect central nervous system through systemic regulation in addition to the vagal pathway.Notably,emerging evidence suggests that rumen microbiota dysbiosis under stress is associated with abnormal behavior,altered hormonal and neurotransmitter levels.In this review,we introduce the concept of the rumen-microbiome-brain axis by comparing the anatomical structures and microbial characteristics of the intestine and the rumen,emphasizing the neuroactive potential of rumen microbiome and underlying mechanisms.Advances in this frontier hold tremendous promise to reveal a novel dimension of the gut-microbiome-brain axis,providing transformative opportunities to improve ruminant welfare,productivity,and agricultural sustainability.
基金financially supported by the fund from the Project of Evonik Operations GmbH(34.63.21010)Natural Science Foundation of Sichuan Province(2024NSFSC0304)。
文摘Background As probiotics,Bacillus strains may regulate some physiological functions in animals.This study aimed to evaluate whether dietary supplementation with a Bacillus-based probiotic could alleviate gut damage induced by rotavirus(RV)infection in piglets.Twenty-four piglets were randomly assigned into 2 groups fed with the basal diet(n=16)and the diet containing 10^(9) colony-forming unit Bacillus spores/kg(n=8).On d 8,8 piglets fed with the diet supplemented with Bacillus-based probiotic and 8 piglets fed with basal diet were orally infused with RV,while the residue piglets had oral gavage of sterile essential medium.The trial duration was 12 d.Results RV challenge induced diarrhea,significantly destroyed the morphology of jejunal mucosa(P<0.05),significantly increased RV-antibody and RV non-structural protein 4 of jejunal mucosa(P<0.05),significantly impaired antioxidant capacity(including malondialdehyde level,total antioxidant capacity and catalase activity),immunity(such as interleukin 2,interleukin 4 and secreted immunoglobulin A levels),mucins and the m RNA expression of tightjunction-related(such as Zonula occludens 1,occludin)and apoptotic-related(including B-cell lymphoma/leukaemia-2-associated X protein,B cell lymphoma/leukaemia-2,cysteinyl aspartate specific proteinases)genes of jejunal mucosa(P<0.05),and,to some extents,affected the bacteria community structure and abundance of ileal digesta in piglets.However,Bacillus-based probiotic administration could significantly attenuate the negative effects of RV infection on gut health of piglets(P<0.05).Conclusions These findings suggested that supplementing Bacillus-based probiotic in the diet could decrease diarrhea rate,and improve gut health in weaned piglets,which was associated with regulating intestinal antioxidant capacity,apoptosis,and microbiota.
基金financial support from the Postdoctoral Fund of Hebei Medical University(30705010038)the Chunyu Project Initial Funding of Hebei Medical University(CYQD2023012)+3 种基金the Science Research Project of Hebei Education Department(QN2025145)the Hebei Yanzhao Golden Platform Talent Gathering Plan Backbone Talent Project(B2024003013)the Natural Science Foundation of Hebei Province(H2024206375,C2022206018,H2023206068)the Traditional Chinese Medicine Administration Project of Hebei Province(2025427).
文摘Glehniae Radix has a wide range of pharmaceutical applications,and research on its main components has mainly focused on coumarins,alkaloids,lignans,and flavonoids,while neglecting the research on polysaccharides.Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation,antioxidant,anti-inflammatory and other aspects.Herein,the rat model of ulcerative colitis(UC)was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide(GLP)from the perspectives of inflammatory factors,intestinal tissue morphology,and microflora changes.The polysaccharides are mainly composed of galacturonic acid,rhamnose,glucose,galactose,and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9,and GLP could downregulate the expression pro-inflammatory factors(interleukin 6,tumor necrosis factorα,and interferonγ)and significantly upregulate the expression of antiinflammatory factor(interleukin 10).In addition,Glehniae Radix aqueous extract(GLA),GLP with low dosage and GLP with high dosage(GLPH)could increase the number of goblet cells,enhance the integrity of crypt structure,and reverse the status of inflammatory infiltrating cells.Moreover,GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats,and appropriately downregulate Lachnospiraceae_NK4A136_group,thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment.Our findings not only be valuable as theoretical materials for the further clinical applications of GLP,but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.
