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
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
Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting...Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 and SLAM_phiST56)and a probiotic bacterium Limosilactobacillus reuteri(SLAM_LAR11)in a chick model challenged with Salmonella enterica serovar Typhimurium infection.Results Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast with phage-only treatment,the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy(P<0.0001)and alleviated infection-associated splenomegaly(P=0.028)and hepatomegaly(P=0.011).In the ileum,the villus height-to-crypt depth ratio(VH/CD)increased significantly(P=0.044).In the colon,expression of tight-junction genes OCLN(P=0.014),TJP1(P<0.0001),and MUC2(P=0.011)was elevated,whereas the pro-inflammatory cytokine IL6 was reduced(P=0.018).These improvements were accompanied,in the cecum,by trends toward decreases in Escherichia-Shigella(P=0.09)and Clostridium(P=0.16)and a trend toward an increase in Blautia(P=0.11);additionally,in the ileum,Lactobacillus(P=0.037)and Blautia(P=0.016)increased significantly,yielding a more balanced microbiota than with phage-only treatment.Consistently,levels of functional metabolites,including acetic acid(LDA=3.32)and lactic acid(LDA=5.29),were increased.Conclusion Taken together,these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.展开更多
Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a n...Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
Background Salmonella enteritidis is a prevalent foodborne pathogen causing diseases in humans and poultry globally.While clove extract is known for its anti-inflammatory properties,its specific effects on gut injury ...Background Salmonella enteritidis is a prevalent foodborne pathogen causing diseases in humans and poultry globally.While clove extract is known for its anti-inflammatory properties,its specific effects on gut injury and underlying mechanisms are not well understood.Methods A total of 432 one-day-old male fast-growing yellow-feathered broilers with similar body weight were randomly assigned to 6 groups,the CON and S.E were fed a basal diet;the CE and S.E+CE received 300 mg/kg of clove extract in their diets;and the EUG and S.E+EUG had 180 mg/kg of eugenol added to their basal diets.Moreover,a newly established ex vivo culture model for chick intestinal organoids(IOs)was used to evaluate intestinal stem cell(ISC)activity.Results Salmonella enteritis infection significantly reduced the growth performance and induced severe intestinal mucosa injury(P<0.05).Dietary supplemented with clove extract or eugenol significantly improved average daily weight gain and feed intake,enhanced the structure and barrier function of the jejunum,reduced the bacterial load and diarrhea scores,promoted the proliferation and differentiation of ISCs,and diminished the efficiency,surface area,budding efficiency,and number of buds of intestinal organoids(P<0.05).Both clove extract and eugenol downregulated the protein expression of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α.They also inhibited the excessive activation of the JAK2/STAT3 signaling pathway induced by Salmonella enteritidis infection in the jejunum tissues and crypts of chicks(P<0.05).Conclusions Eugenol,the active component in clove extract,alleviates intestinal inflammation by inhibiting the excessive activation of the JAK2/STAT3 signaling pathway.It promotes the proliferation and differentiation of ISCs,suppresses apoptosis,and accelerates ISCs-driven intestinal epithelial renewal in chicks,thereby maintaining the structural integrity and functional normalcy of the intestine.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.展开更多
Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent im...Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.展开更多
Background As an essential source of nutrients for young mammals,milk possesses a variety of biological functions.Recently identified milk-derived small extracellular vesicles(sEV)have shown potential regulatory effec...Background As an essential source of nutrients for young mammals,milk possesses a variety of biological functions.Recently identified milk-derived small extracellular vesicles(sEV)have shown potential regulatory effects on intestinal health.Current studies have highlighted the functional roles of milk-derived sEV and their RNA cargo in promoting intestinal health.However,there is a paucity of research demonstrating how milk-derived sEV influence intestinal barrier function through the transport of circRNAs.Results In this study,we aimed to investigate the effects of porcine milk sEV(PM-sEV)circRNA on intestinal barrier function.We systematically identified the circRNAs involved in this process and analyzed the miRNAs through which PM-sEV deliver circRNAs to regulate intestinal barrier function.Our findings revealed that PM-sEV promote the expression of the intestinal tight junction proteins ZO-1 and Occludin,both in vivo(mice)and in vitro(IPEC-J2).When PMsEV RNA was reduced using ultrasound treatment,their ability to enhance intestinal barrier function was significantly reduced.Bioinformatics analysis showed that circ-0000197,present in PM-sEV,can target miR-429,while miR-429 has the ability to target the 3’-UTR of ZO-1 and Occludin.Furthermore,experiments involving the overexpression or inhibition of the relevant non-coding RNAs(ncRNAs)demonstrated that circ-0000197 significantly enhances intestinal barrier function,whereas miR-429 exerts an inhibitory effect on this function.Overall,our findings identify circ-0000197 in PM-sEV as a crucial circRNA that regulates intestinal barrier function by inhibiting miR-429.Circ-0000197 carried by PM-sEV acts as a competing endogenous RNA(ceRNA)that regulates the expression of ZO-1 and Occludin by sponging miR-429,thereby promoting intestinal barrier function at both the cellular and in vivo levels.Conclusions These findings emphasize the vital role of circRNAs transported through milk-derived sEV in regulating intestinal health,offering new avenues for developing innovative functional milk components.This mechanism also underscores the importance of PM-sEV carrying circ-0000197 in preserving intestinal barrier integrity.Collectively,this study enhances our understanding of the complex regulatory networks involving PM-sEV carrying circRNAs and their impact on intestinal health.展开更多
The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms...The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms.We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis.Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier.Experimentally,we demonstrated that EWPH effectively protects against dextran sulfate sodium(DSS)-induced intestinal barrier damage in mice.The protective mechanisms involve not only the inhibition of the Toll-like receptor 4(TLR4)-nuclear factor-kB(NF-kB)/mitogen-activated protein kinases(MAPK)signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage,including phosphorylated-SRC proto-oncogene(p-SRC),phosphorylated-signal transducer and activator of transcription 3(p-STAT3),Caspase-3,and matrix metalloproteinase-9(MMP9),thereby mitigating intestinal inflammation and mucosal barrier injury.This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.展开更多
Plant-based milk is rich in polyunsaturated fatty acids,polyphenols and other bioactive compounds.This study investigated the effect of 3 plant-based milk(flaxseed milk,oat milk and soy milk)on the ceftriaxone-induced...Plant-based milk is rich in polyunsaturated fatty acids,polyphenols and other bioactive compounds.This study investigated the effect of 3 plant-based milk(flaxseed milk,oat milk and soy milk)on the ceftriaxone-induced intestinal disorders,and compared the regulation patterns associated with gut microbiome and metabolome.The results showed plant-based milk alleviated the ceftriaxone caused cecum swelling,colonic tissue damage and intestinal microecological disorders.Meanwhile,administered plant-based milk decreased levels of pro-inflammatory cytokine(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and oxidative stresses(malondialdehyde(MDA)and myeloperoxidase(MPO)in the colon,as well as increasing the levels of tight junction proteins(Occludin,Claudin-1,and ZO-1)in the colon.Moreover,administration of plant-based milk modulated the intestinal microbiota by promoting the relative levels of beneficial bacteria(Bifidobacterium),and inhibiting the harmful bacteria genus(Enterococcus).Furthermore,plant-based milk treatment significantly modulated glycerophospholipids metabolism(e.g.glycerophosphocholine)and arachidonic acid metabolism(e.g.prostaglandin G2 and arachidonic acid)in the serum.In conclusion,plant-based milk could alleviate antibiotic-related imbalance of barrier function damage,gut microbiota disorders and the reduction of metabolic disorders,which lays a foundation for exploring anti-inflammatory and intestinal micro-ecological approach to plant-based milk.展开更多
BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progre...BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progression of UC remains to be fully eluci-dated.AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.METHODS A KRT1 antibody concentration gradient test,along with a dextran sulfate sodium(DSS)-induced animal model,was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system(KKS)and the cleavage of bradykinin(BK)/high molecular weight kininogen(HK)in UC.RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation,induced apoptosis,reduced HK expression,and increased BK expression.It further downregulated intestinal barrier proteins,including occludin,zonula occludens-1,and claudin,and negatively impacted the coagulation factor XII.These changes led to enhanced activation of BK and HK cleavage,thereby intensifying KKS-mediated inflammation in UC.In the DSS-induced mouse model,administration of KRT1 antibody mitigated colonic injury,increased colon length,alleviated weight loss,and suppressed inflammatory cytokines such as interleukin(IL)-1,IL-6,tumor necrosis factor-α.It also facilitated repair of the intestinal barrier,reducing DSS-induced injury.CONCLUSION KRT1 inhibits BK expression,suppresses inflammatory cytokines,and enhances markers of intestinal barrier function,thus ameliorating colonic damage and maintaining barrier integrity.KRT1 is a viable therapeutic target for UC.展开更多
Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.T...Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.Thus,the present study aimed to assess the palliative effects of Lactobacillus rhamnosus MP108 on UC in mice and to explore its potential mechanisms.The results showed that L.rhamnosus MP108 ameliorated the symptoms of UC,including preventing body weight loss,disease activity index(DAI)elevation,and colon shortening,and attenuated colonic pathological damage.L.rhamnosus MP108 dramatically increased the number of goblet cells,MUC2 level,and tight junction protein level in the colon and remarkably inhibited epithelial cell apoptosis,thereby strengthening the intestinal barrier.L.rhamnosus MP108 pronouncedly diminished pro-inflammatory cytokine levels and strikingly augmented anti-inflammatory cytokine levels,in turn suppressing inflammation.Furthermore,L.rhamnosus MP108 conspicuously boosted the proportion of short-chain fatty acids(SCFAs)producers in gut microbiota,contributing to increased levels of acetate and butyrate.Therefore,L.rhamnosus MP108 might alleviate UC via improving the intestinal barrier,inhibiting inflammation,and modulating intestinal microbiota.展开更多
This study investigated the therapeutic effects on metabolic syndrome(MetS)and the impact on the intestinal barrier and gut microbiota of Fu brick tea aqueous extracts(FTE)on MetS in rats fed with a high-fat diet(HFD)...This study investigated the therapeutic effects on metabolic syndrome(MetS)and the impact on the intestinal barrier and gut microbiota of Fu brick tea aqueous extracts(FTE)on MetS in rats fed with a high-fat diet(HFD).Here,the results showed that FTE supplement significantly reduced HFD-induced weight gain,adiposity,dyslipidemia,fasting blood glucose(FBG)increment,and non-alcoholic fatty liver disease(NAFLD).Moreover,FTE supplement resulted in a decline in lipopolysaccharide(LPS)level and attenuation of colonic inflammation and oxidative stress to protect the intestinal barrier function.FTE supplement also maintained the intestinal barrier integrity by improving histological appearance and promoting ZO-1,Occludin,and Claudin-1 protein expression levels.Meanwhile,FTE supplement alleviated the gut microbiota dysbiosis by enhancing the Firmicutes/Bacteroidetes(F/B)ratio and stimulating the colonization of probiotic bacteria such as Akkermansia,Lactobacillus,Adlercreutzia,and Bacteroides.These findings collectively suggest that Fu brick tea could alleviate MetS and MetS-associated traits with the mechanism relevant to the protection of intestinal barrier and gut microbiota regulation.展开更多
This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier...This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.展开更多
Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A complet...Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.展开更多
The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran so...The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.展开更多
Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the i...Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the infiltration of inflammatory cells into the intestinal mucosa and thus help enhancing intestinal barrier which could be damaged in some metabolic diseases.In this study,the influence of anthocyanin(administered orally)on the alterations(including structure and permeability)of the intestinal mucosa in mice in response to a high fat-high cholesterol(HFHC)diet was investigated.Primary T helper 17(Th17)cells were isolated from mouse intestine tissues to observe the modulatory role of anthocyanin through the transcription phosphorylated STAT 3(p-STAT3).The results indicated that anthocyanin significantly alleviated HFHC-induced impairment in the intestinal structures and permeability in a dose-dependent manner;moreover,anthocyanin appeared to inhibit HFHC induced the expression of p-STAT3,thereby disturbing Th17 cell differentiation.In high-fat diet(HFD,cholesterol level non-modified)-challenged mice selective p-STAT3 inhibitor significantly reversed the effects of anthocyanin,which were decreased amount of interleukin(IL)-17A(produced and released from Th17 cells)and the protected intestinal structure/function.In summary,the results of this study suggest that anthocyanin may attenuate the damage of intestinal barrier in HFHC mice through regulating intestinal STAT3-Th17-IL-17A signal transduction pathway.展开更多
Bifidobacterium longum subsp.infantis is a commensal bacterium that predominates in the infant gut,playing a critical role in both preventing foreign infections and facilitating immune development.This study aimed to ...Bifidobacterium longum subsp.infantis is a commensal bacterium that predominates in the infant gut,playing a critical role in both preventing foreign infections and facilitating immune development.This study aimed to explore the effects of B.longum subsp.infantis supplementation on interferon-beta(IFN-β)secretion and intestinal barrier improvement in growing mice.Female and male mice were orally administered either saline or B.longum subsp.infantis CCFM1269 or I5TI(1×10^(9) CFU/mice per day,n=8)from 1-week-age until 3-,4-,and 5-week-age.RNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2'-5'oligoadenylate synthetase(OAS).Additionally,CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLR4-TRIF-dependent signaling pathway.However,this effect was not observed in 4-and 5-week-old mice.Furthermore,both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-,4-,and 5-week-old mice.In summary,the results of this study suggested that B.longum subsp.infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.展开更多
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 Research Foundation of Korea(NRF)grant funded by the National Research Foundation of Korea Grantfunded by the Korean government(MEST)(NRF-2021R1A2C3011051)by the Korea government(MSIT)(No.RS-2023-00218476)。
文摘Background The rapid emergence of multidrug-resistant Salmonella in poultry demands alternative control strategies beyond conventional antibiotics.In this study,we evaluated a combination of lytic Salmonella-infecting bacteriophages(SLAM_phi ST45 and SLAM_phiST56)and a probiotic bacterium Limosilactobacillus reuteri(SLAM_LAR11)in a chick model challenged with Salmonella enterica serovar Typhimurium infection.Results Co-administration with two-phage cocktail and a probiotic showed markedly reduced Salmonella colonization in the gut and systemic organs of chicks,comparable to the effect of phage-only treatment.In contrast with phage-only treatment,the combined therapy significantly improved the rate of body-weight change from the day of infection to necropsy(P<0.0001)and alleviated infection-associated splenomegaly(P=0.028)and hepatomegaly(P=0.011).In the ileum,the villus height-to-crypt depth ratio(VH/CD)increased significantly(P=0.044).In the colon,expression of tight-junction genes OCLN(P=0.014),TJP1(P<0.0001),and MUC2(P=0.011)was elevated,whereas the pro-inflammatory cytokine IL6 was reduced(P=0.018).These improvements were accompanied,in the cecum,by trends toward decreases in Escherichia-Shigella(P=0.09)and Clostridium(P=0.16)and a trend toward an increase in Blautia(P=0.11);additionally,in the ileum,Lactobacillus(P=0.037)and Blautia(P=0.016)increased significantly,yielding a more balanced microbiota than with phage-only treatment.Consistently,levels of functional metabolites,including acetic acid(LDA=3.32)and lactic acid(LDA=5.29),were increased.Conclusion Taken together,these findings demonstrate that phage-probiotic co-administration not only enhances the clearance of multidrug-resistant Salmonella more effectively than phage treatment alone but also promotes intestinal health,highlighting its potential as an antibiotic-alternatives strategy to improve intestinal health and ensure food safety in poultry production systems.
基金funded by Beijing Natural Science Foundation(6252001)Guangdong Basic and Applied Basic Research Foundation(2022A1515140021)Natural Science Foundation of China(31871772).
文摘Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
基金funded by the National Natural Science Foundation of China(32372902)the National Key Research and Development Program of China(2021YFD1300405).
文摘Background Salmonella enteritidis is a prevalent foodborne pathogen causing diseases in humans and poultry globally.While clove extract is known for its anti-inflammatory properties,its specific effects on gut injury and underlying mechanisms are not well understood.Methods A total of 432 one-day-old male fast-growing yellow-feathered broilers with similar body weight were randomly assigned to 6 groups,the CON and S.E were fed a basal diet;the CE and S.E+CE received 300 mg/kg of clove extract in their diets;and the EUG and S.E+EUG had 180 mg/kg of eugenol added to their basal diets.Moreover,a newly established ex vivo culture model for chick intestinal organoids(IOs)was used to evaluate intestinal stem cell(ISC)activity.Results Salmonella enteritis infection significantly reduced the growth performance and induced severe intestinal mucosa injury(P<0.05).Dietary supplemented with clove extract or eugenol significantly improved average daily weight gain and feed intake,enhanced the structure and barrier function of the jejunum,reduced the bacterial load and diarrhea scores,promoted the proliferation and differentiation of ISCs,and diminished the efficiency,surface area,budding efficiency,and number of buds of intestinal organoids(P<0.05).Both clove extract and eugenol downregulated the protein expression of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α.They also inhibited the excessive activation of the JAK2/STAT3 signaling pathway induced by Salmonella enteritidis infection in the jejunum tissues and crypts of chicks(P<0.05).Conclusions Eugenol,the active component in clove extract,alleviates intestinal inflammation by inhibiting the excessive activation of the JAK2/STAT3 signaling pathway.It promotes the proliferation and differentiation of ISCs,suppresses apoptosis,and accelerates ISCs-driven intestinal epithelial renewal in chicks,thereby maintaining the structural integrity and functional normalcy of the intestine.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier repair.
基金supported by the Hunan Provincial Science and Technology Major Special Fund(2021SK1020)the Natural Science Foundation of Hunan Province(2023JJ30948)+1 种基金the Health Commission of Hunan Province(202203014687)the International Medical Exchange Cardiovascular Multidisciplinary Integrated Thinking Research Foundation(Z-2016-23-2101-20),China.
文摘Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.
基金supported by the National key research and development program(2022YFD1300401)Natural Science Foundation of Guangdong Province(2023 A1515012127,2024 A1515010510,2025 A1515011832)+1 种基金National Natural Science Foundation of China(32372958)Visiting Scholar Fund by China Scholarship Council(202008440191).
文摘Background As an essential source of nutrients for young mammals,milk possesses a variety of biological functions.Recently identified milk-derived small extracellular vesicles(sEV)have shown potential regulatory effects on intestinal health.Current studies have highlighted the functional roles of milk-derived sEV and their RNA cargo in promoting intestinal health.However,there is a paucity of research demonstrating how milk-derived sEV influence intestinal barrier function through the transport of circRNAs.Results In this study,we aimed to investigate the effects of porcine milk sEV(PM-sEV)circRNA on intestinal barrier function.We systematically identified the circRNAs involved in this process and analyzed the miRNAs through which PM-sEV deliver circRNAs to regulate intestinal barrier function.Our findings revealed that PM-sEV promote the expression of the intestinal tight junction proteins ZO-1 and Occludin,both in vivo(mice)and in vitro(IPEC-J2).When PMsEV RNA was reduced using ultrasound treatment,their ability to enhance intestinal barrier function was significantly reduced.Bioinformatics analysis showed that circ-0000197,present in PM-sEV,can target miR-429,while miR-429 has the ability to target the 3’-UTR of ZO-1 and Occludin.Furthermore,experiments involving the overexpression or inhibition of the relevant non-coding RNAs(ncRNAs)demonstrated that circ-0000197 significantly enhances intestinal barrier function,whereas miR-429 exerts an inhibitory effect on this function.Overall,our findings identify circ-0000197 in PM-sEV as a crucial circRNA that regulates intestinal barrier function by inhibiting miR-429.Circ-0000197 carried by PM-sEV acts as a competing endogenous RNA(ceRNA)that regulates the expression of ZO-1 and Occludin by sponging miR-429,thereby promoting intestinal barrier function at both the cellular and in vivo levels.Conclusions These findings emphasize the vital role of circRNAs transported through milk-derived sEV in regulating intestinal health,offering new avenues for developing innovative functional milk components.This mechanism also underscores the importance of PM-sEV carrying circ-0000197 in preserving intestinal barrier integrity.Collectively,this study enhances our understanding of the complex regulatory networks involving PM-sEV carrying circRNAs and their impact on intestinal health.
文摘The intestinal barrier is crucial for homeostasis.This study aimed to investigate the protective effects of earthworm protein hydrolysates(EWPH)on the intestinal mucosal barrier and elucidate the underlying mechanisms.We first hydrolyzed earthworm protein using alcalase and identified the primary peptide components of EWPH through Nano LC-MS/MS analysis.Network pharmacology and bioinformatics approaches were employed to predict potential targets associated with the intestinal mucosal barrier.Experimentally,we demonstrated that EWPH effectively protects against dextran sulfate sodium(DSS)-induced intestinal barrier damage in mice.The protective mechanisms involve not only the inhibition of the Toll-like receptor 4(TLR4)-nuclear factor-kB(NF-kB)/mitogen-activated protein kinases(MAPK)signaling pathway in the intestinal epithelium but also the suppression of other key molecules implicated in intestinal mucosal barrier damage,including phosphorylated-SRC proto-oncogene(p-SRC),phosphorylated-signal transducer and activator of transcription 3(p-STAT3),Caspase-3,and matrix metalloproteinase-9(MMP9),thereby mitigating intestinal inflammation and mucosal barrier injury.This study provides evidence that EWPH have the potential to safeguard the intestinal barrier hemostasis.
基金funded by Earmarked Fund for China Agriculture Research System(CARS-14)the Central Public-interest Scientific Institution Basal Research Fund(11021716001100B)。
文摘Plant-based milk is rich in polyunsaturated fatty acids,polyphenols and other bioactive compounds.This study investigated the effect of 3 plant-based milk(flaxseed milk,oat milk and soy milk)on the ceftriaxone-induced intestinal disorders,and compared the regulation patterns associated with gut microbiome and metabolome.The results showed plant-based milk alleviated the ceftriaxone caused cecum swelling,colonic tissue damage and intestinal microecological disorders.Meanwhile,administered plant-based milk decreased levels of pro-inflammatory cytokine(tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)and oxidative stresses(malondialdehyde(MDA)and myeloperoxidase(MPO)in the colon,as well as increasing the levels of tight junction proteins(Occludin,Claudin-1,and ZO-1)in the colon.Moreover,administration of plant-based milk modulated the intestinal microbiota by promoting the relative levels of beneficial bacteria(Bifidobacterium),and inhibiting the harmful bacteria genus(Enterococcus).Furthermore,plant-based milk treatment significantly modulated glycerophospholipids metabolism(e.g.glycerophosphocholine)and arachidonic acid metabolism(e.g.prostaglandin G2 and arachidonic acid)in the serum.In conclusion,plant-based milk could alleviate antibiotic-related imbalance of barrier function damage,gut microbiota disorders and the reduction of metabolic disorders,which lays a foundation for exploring anti-inflammatory and intestinal micro-ecological approach to plant-based milk.
基金Supported by the National Natural Science Foundation of China,No.82160113the“Xingdian Talents”Support Project of Yunnan Province,No.RLMY20220007+1 种基金the Yunnan Province Clinical Research Center for Digestive Diseases,No.202102AA100062the Applied Basic Research Projects of Yunnan Province,No.2019FE001-039.
文摘BACKGROUND External factors in ulcerative colitis(UC)exacerbate colonic epithelial permea-bility and inflammatory responses.Keratin 1(KRT1)is crucial in regulating these alterations,but its specific role in the progression of UC remains to be fully eluci-dated.AIM To explore the role and mechanisms of KRT1 in the regulation of colonic epithelial permeability and inflammation in UC.METHODS A KRT1 antibody concentration gradient test,along with a dextran sulfate sodium(DSS)-induced animal model,was implemented to investigate the role of KRT1 in modulating the activation of the kallikrein kinin system(KKS)and the cleavage of bradykinin(BK)/high molecular weight kininogen(HK)in UC.RESULTS Treatment with KRT1 antibody in Caco-2 cells suppressed cell proliferation,induced apoptosis,reduced HK expression,and increased BK expression.It further downregulated intestinal barrier proteins,including occludin,zonula occludens-1,and claudin,and negatively impacted the coagulation factor XII.These changes led to enhanced activation of BK and HK cleavage,thereby intensifying KKS-mediated inflammation in UC.In the DSS-induced mouse model,administration of KRT1 antibody mitigated colonic injury,increased colon length,alleviated weight loss,and suppressed inflammatory cytokines such as interleukin(IL)-1,IL-6,tumor necrosis factor-α.It also facilitated repair of the intestinal barrier,reducing DSS-induced injury.CONCLUSION KRT1 inhibits BK expression,suppresses inflammatory cytokines,and enhances markers of intestinal barrier function,thus ameliorating colonic damage and maintaining barrier integrity.KRT1 is a viable therapeutic target for UC.
基金supported by the National Natural Science Foundation of China(32021005)111 Project(BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Ulcerative colitis(UC)is a long-term inflammatory disorder that has evolved into a worldwide challenge.The development of new therapies against UC is imperative as all current therapies for UC are flawed in some way.Thus,the present study aimed to assess the palliative effects of Lactobacillus rhamnosus MP108 on UC in mice and to explore its potential mechanisms.The results showed that L.rhamnosus MP108 ameliorated the symptoms of UC,including preventing body weight loss,disease activity index(DAI)elevation,and colon shortening,and attenuated colonic pathological damage.L.rhamnosus MP108 dramatically increased the number of goblet cells,MUC2 level,and tight junction protein level in the colon and remarkably inhibited epithelial cell apoptosis,thereby strengthening the intestinal barrier.L.rhamnosus MP108 pronouncedly diminished pro-inflammatory cytokine levels and strikingly augmented anti-inflammatory cytokine levels,in turn suppressing inflammation.Furthermore,L.rhamnosus MP108 conspicuously boosted the proportion of short-chain fatty acids(SCFAs)producers in gut microbiota,contributing to increased levels of acetate and butyrate.Therefore,L.rhamnosus MP108 might alleviate UC via improving the intestinal barrier,inhibiting inflammation,and modulating intestinal microbiota.
基金supported by the Earmarked Fund for the Modern Agricultural Industry Technology System(CARS19),Research on Quality Chemical Characteristics and Healthy Function of Xianyang Brick Tea(2021kjc-js231)Research on Metabolite Alteration and Mechanism in Fu Brick Tea under the Action of Eurotium cristatum(31471706).
文摘This study investigated the therapeutic effects on metabolic syndrome(MetS)and the impact on the intestinal barrier and gut microbiota of Fu brick tea aqueous extracts(FTE)on MetS in rats fed with a high-fat diet(HFD).Here,the results showed that FTE supplement significantly reduced HFD-induced weight gain,adiposity,dyslipidemia,fasting blood glucose(FBG)increment,and non-alcoholic fatty liver disease(NAFLD).Moreover,FTE supplement resulted in a decline in lipopolysaccharide(LPS)level and attenuation of colonic inflammation and oxidative stress to protect the intestinal barrier function.FTE supplement also maintained the intestinal barrier integrity by improving histological appearance and promoting ZO-1,Occludin,and Claudin-1 protein expression levels.Meanwhile,FTE supplement alleviated the gut microbiota dysbiosis by enhancing the Firmicutes/Bacteroidetes(F/B)ratio and stimulating the colonization of probiotic bacteria such as Akkermansia,Lactobacillus,Adlercreutzia,and Bacteroides.These findings collectively suggest that Fu brick tea could alleviate MetS and MetS-associated traits with the mechanism relevant to the protection of intestinal barrier and gut microbiota regulation.
基金Supported by Major Project of Zhongshan Science and Technology Bureau(2021B3009).
文摘This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.
基金Key International Cooperation Program of the National Natural Science Foundation of China(32120103011)Jiangsu Shuang Chuang Tuan Dui program(JSSCTD202147)+1 种基金Jiangsu Shuang Chuang Ren Cai program(JSSCRC2021541)Initiation Funds of Yangzhou University for Distinguished Scientists.
文摘Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.
基金project was supported by the National Key Research and Development Program(2021YFD2100700)。
文摘The aim of this paper was to study the effect of combination of Lactobacillus strains and tryptophan(Trp)-rich diet on the intestinal barrier function of Balb/c mice exposed to a cocktail of antibiotics and dextran sodium sulfate.Several Lactobacillus strains isolated from the healthy human fecal sample was found to utilize Trp to produce indole derivatives.The results of Trp metabolism indicated that the ability of Lactobacillus to metabolize Trp to produce indole-3-lactic acid(ILA),indole-3-carboxaldehyde(I3C),and indole-3-acetic acid varies in vitro and in vivo.The effect of Lactobacillus with high-yielding indole derivatives on disease activity index,colon length,and intestinal permeability was significantly better than that of Lactobacillus with low-yielding indole derivatives in a high Trp diet.And Lactobacillus combined with Trp intervention also had a certain regulatory effect on the intestinal flora of male BALB/c mice.Among them,Lactiplantibacillus plantarum DPUL-S164 produced more ILA both in vivo and in vitro,and the combination of L.plantarum DPUL-S164 and Trp significantly decreased the expression level of the serum pro-inflammatory cytokine interleukin(IL)-6 and increased the expression level of the anti-inflammatory cytokine IL-10,significantly improved the number of goblet cells in the mouse mucous layer and increased mucin and tight junction protein expression.Furthermore,L.plantarum DPUL-S164 combined with Trp intervention activated the aryl hydrocarbon receptors(Ah R)signaling pathway.Furthermore,we found that the expression of colonic tight junction protein was positively correlated with the expression of colonic Ah R,and the expression of Ah R was positively correlated with the concentrations of ILA and I3C in vivo.Therefore,we conclude that the ILA as Ah R ligand produced by L.plantarum DPUL-S164 regulated the Ah R pathway,thus up-regulating the expression of the tight junction protein and protecting the integrity of the epithelial barrier.
基金supported by the National Natural Science Foundation of China(81973022 and 81730090)。
文摘Anthocyanin,as a typical food bioactive molecule,is capable of reversing inflammatory,oxidative and allergic condition thus contributes to intestinal health.We were wondering whether anthocyanin has influence on the infiltration of inflammatory cells into the intestinal mucosa and thus help enhancing intestinal barrier which could be damaged in some metabolic diseases.In this study,the influence of anthocyanin(administered orally)on the alterations(including structure and permeability)of the intestinal mucosa in mice in response to a high fat-high cholesterol(HFHC)diet was investigated.Primary T helper 17(Th17)cells were isolated from mouse intestine tissues to observe the modulatory role of anthocyanin through the transcription phosphorylated STAT 3(p-STAT3).The results indicated that anthocyanin significantly alleviated HFHC-induced impairment in the intestinal structures and permeability in a dose-dependent manner;moreover,anthocyanin appeared to inhibit HFHC induced the expression of p-STAT3,thereby disturbing Th17 cell differentiation.In high-fat diet(HFD,cholesterol level non-modified)-challenged mice selective p-STAT3 inhibitor significantly reversed the effects of anthocyanin,which were decreased amount of interleukin(IL)-17A(produced and released from Th17 cells)and the protected intestinal structure/function.In summary,the results of this study suggest that anthocyanin may attenuate the damage of intestinal barrier in HFHC mice through regulating intestinal STAT3-Th17-IL-17A signal transduction pathway.
基金funded by the National Key R&D Program of China(2021YFD2100700)National Natural Science Foundation of China(32021005)+1 种基金111 project(BP0719028)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Bifidobacterium longum subsp.infantis is a commensal bacterium that predominates in the infant gut,playing a critical role in both preventing foreign infections and facilitating immune development.This study aimed to explore the effects of B.longum subsp.infantis supplementation on interferon-beta(IFN-β)secretion and intestinal barrier improvement in growing mice.Female and male mice were orally administered either saline or B.longum subsp.infantis CCFM1269 or I5TI(1×10^(9) CFU/mice per day,n=8)from 1-week-age until 3-,4-,and 5-week-age.RNA sequencing analysis revealed that CCFM1269 exhibited potential antiviral capacity through increasing 2'-5'oligoadenylate synthetase(OAS).Additionally,CCFM1269 supplementation significantly increased colonic IFN-β levels which combined with OAS in 3-week-old female and male mice by activating the TLR4-TRIF-dependent signaling pathway.However,this effect was not observed in 4-and 5-week-old mice.Furthermore,both CCFM1269 were found to modulate the gut microbiota composition and enhance the intestinal barrier function in 3-,4-,and 5-week-old mice.In summary,the results of this study suggested that B.longum subsp.infantis CCFM1269 promoting intestinal barrier and releasing IFN-β in growing mice was in a strain-specific and time-dependent manner.
