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 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
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
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
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
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
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
Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massiv...Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.展开更多
Background： Colibacillosis caused by enterotoxigenic Escherichia coil （E. coil} results in economic losses in the poultry industry. Antibiotics are usually used to control colibacillosis, however, E. coli has varyin...Background： Colibacillosis caused by enterotoxigenic Escherichia coil （E. coil} results in economic losses in the poultry industry. Antibiotics are usually used to control colibacillosis, however, E. coli has varying degrees of resistance to different antibiotics. Therefore the use of probiotics is becoming accepted as an alternative to antibiotics. In this study, we evaluated the effects of Clostfidium butyricum （C. butyficum） on growth performance, immune response, intestinal barrier function, and digestive enzyme activity in broiler chickens challenged with Eschefichia coli （E. coil） K88. Methods： The chickens were randomly divided into four treatment groups for 28 days. Negative control treatment （NC） consisted of birds fed a basal diet without E. coil K88 challenge and positive control treatment （PC） consisted of birds fed a basal diet and challenged with E. coil K88. C. buO/ricum probiotic treatment （CB） consisted of birds fed a diet containing 2 x 107 cfu C. buO/ricum/kg of diet and challenged with E. coil K88. Colistin sulfate antibiotic treatment （CS） consisted of birds fed a diet containing 20 mg colistin sulfate/kg of diet and challenged with E. coil K88. Results： The body weight （BW） and average day gain （ADG） in the broilers of CB group were higher （P 〈 0.05） than the broilers in the PC group overall except the ADG in the 14-21 d post-challenge. The birds in CB treatment had higher （P 〈 0.05） concentration of tumor necrosis factor-a （TNF-a） at 3 and 7 d post-challenge, and higher （P 〈 0.05） concentration of interleukin-4 （IL-4） at 14 d post-challenge than those in the PC treatment group. The concentration of serum endotoxin in CB birds was lower （P 〈 0.05） at 21 d post-challenge, and the concentrations of serum diamine oxidase in CB birds were lower （P 〈 0.05） at 14 and 21 d post-challenge than in PC birds. Birds in CB treatment group had higher （P 〈 0.05） jejunum villi height than those in PC, NC, or CS treatment at 7, 14, and 21 d post-challenge. In comparison to PC birds, the CB birds had lower （P 〈 0.05） jejunum crypt depth during the whole experiment. The birds in CB or CS treatment group had higher （P 〈 0.05） activities of amylase and protease at 3, 7, and 14 d post-challenge, and higher （P 〈 0.05） activity of lipase at 3, 7 d post-challenge than PC birds.展开更多
BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD...BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.展开更多
BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organ...BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.METHODS Acute colitis was induced by 3%(w/v)dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d.Concurrently,mice with colitis were administered 0.2 mL UCB(400μmol/L)by intra-gastric gavage for 7 d.Disease activity index(DAI)was monitored daily.Mice were sacrificed at the end of the experiment.The length of the colon and weight of the spleen were recorded.Serum level of D-lactate,intestinal digestive proteases activity,and changes to the gut flora were analyzed.In addition,colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.RESULTS Mice treated with UCB had significantly relieved severity of colitis,including lower DAI,longer colon length,and lower spleen weight(colon length:4.92±0.09 cm vs 3.9±0.15 cm;spleen weight:0.33±0.04 vs 0.74±0.04,P<0.001).UCB administration inactivated digestive proteases(chymotrypsin:18.70±0.69 U/g vs44.81±8.60 U/g;trypsin:1.52±0.23 U/g vs 9.05±1.77 U/g,P<0.01),increased expression of tight junction(0.99±0.05 vs 0.57±0.03,P<0.001),decreased serum level of D-lactate(31.76±3.37μmol/L vs 54.25±1.45μmol/L,P<0.001),and lowered histopathological score(4±0.57 vs 7±0.57,P<0.001)and activity of myeloperoxidase(46.79±2.57 U/g vs 110.32±19.19 U/g,P<0.001).UCB also regulated the intestinal microbiota,inhibited expression of tumor necrosis factor(TNF)αand interleukin 1β(TNF-α:52.61±7.81 pg/mg vs 105.04±11.92 pg/mg,interleukin 1β:13.43±1.68 vs 32.41±4.62 pg/mg,P<0.001),decreased expression of Toll-like receptor 4(0.61±0.09 vs 1.07±0.03,P<0.001)and myeloid differentiation primary response gene 88(0.73±0.08 vs 1.01±0.07,P<0.05),and increased expression of TNF-receptor-associated factor 6(0.79±0.02 vs0.43±0.09 P<0.05)and inhibitor of kappa Bα(0.93±0.07 vs 0.72±0.07,P<0.05)in the colon.CONCLUSION UCB can protect intestinal barrier function,regulate normal intestinal homeostasis,and suppress inflammation via the Toll-like receptor 4/nuclear factor-κB signaling pathway.展开更多
AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was desi...AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups： control group （n = 20） and supplemental group （adding Gin and rhGH, n = 22）. Every patient received isocaloric and isonitrogenous standard total parenteral nutrition （TPN） starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein （CRP） levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS： On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group （33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, （1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively）, whereas the increase in serum TNF-α concentration was significantly reduced （41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05）. The increase in L/M ratio was significantly lower in the supplemental group than in the control group （0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05）. Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION： Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.展开更多
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.
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(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 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 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.
基金Supported by the National Natural Science Foundation of China,No.81760120 and No.81960128the Key Program of Science and Technology Department of Jiangxi Province,No.20171BBG70084 and No.20192ACBL20037.
文摘Acute pancreatitis(AP)is a common gastrointestinal disorder.Approximately15%-20%of patients develop severe AP.Systemic inflammatory response syndrome and multiple organ dysfunction syndrome may be caused by the massive release of inflammatory cytokines in the early stage of severe AP,followed by intestinal dysfunction and pancreatic necrosis in the later stage.A study showed that 59%of AP patients had associated intestinal barrier injury,with increased intestinal mucosal permeability,leading to intestinal bacterial translocation,pancreatic tissue necrosis and infection,and the occurrence of multiple organ dysfunction syndrome.However,the real effect of the gut microbiota and its metabolites on intestinal barrier function in AP remains unclear.This review summarizes the alterations in the intestinal flora and its metabolites during AP development and progression to unveil the mechanism of gut failure in AP.
基金supported by the International Cooperation Project of Zhejiang Province(No.2012C14031)Innovative Research Team Program of Zhejiang Province(No.2011R50025)
文摘Background： Colibacillosis caused by enterotoxigenic Escherichia coil （E. coil} results in economic losses in the poultry industry. Antibiotics are usually used to control colibacillosis, however, E. coli has varying degrees of resistance to different antibiotics. Therefore the use of probiotics is becoming accepted as an alternative to antibiotics. In this study, we evaluated the effects of Clostfidium butyricum （C. butyficum） on growth performance, immune response, intestinal barrier function, and digestive enzyme activity in broiler chickens challenged with Eschefichia coli （E. coil） K88. Methods： The chickens were randomly divided into four treatment groups for 28 days. Negative control treatment （NC） consisted of birds fed a basal diet without E. coil K88 challenge and positive control treatment （PC） consisted of birds fed a basal diet and challenged with E. coil K88. C. buO/ricum probiotic treatment （CB） consisted of birds fed a diet containing 2 x 107 cfu C. buO/ricum/kg of diet and challenged with E. coil K88. Colistin sulfate antibiotic treatment （CS） consisted of birds fed a diet containing 20 mg colistin sulfate/kg of diet and challenged with E. coil K88. Results： The body weight （BW） and average day gain （ADG） in the broilers of CB group were higher （P 〈 0.05） than the broilers in the PC group overall except the ADG in the 14-21 d post-challenge. The birds in CB treatment had higher （P 〈 0.05） concentration of tumor necrosis factor-a （TNF-a） at 3 and 7 d post-challenge, and higher （P 〈 0.05） concentration of interleukin-4 （IL-4） at 14 d post-challenge than those in the PC treatment group. The concentration of serum endotoxin in CB birds was lower （P 〈 0.05） at 21 d post-challenge, and the concentrations of serum diamine oxidase in CB birds were lower （P 〈 0.05） at 14 and 21 d post-challenge than in PC birds. Birds in CB treatment group had higher （P 〈 0.05） jejunum villi height than those in PC, NC, or CS treatment at 7, 14, and 21 d post-challenge. In comparison to PC birds, the CB birds had lower （P 〈 0.05） jejunum crypt depth during the whole experiment. The birds in CB or CS treatment group had higher （P 〈 0.05） activities of amylase and protease at 3, 7, and 14 d post-challenge, and higher （P 〈 0.05） activity of lipase at 3, 7 d post-challenge than PC birds.
基金The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board(Approval No.2019082).
文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.
基金Supported by grants from the National Natural Foundation of China,No.81703232
文摘BACKGROUND Unconjugated bilirubin(UCB)is generally considered toxic but has gained recent prominence for its anti-inflammatory properties.However,the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.METHODS Acute colitis was induced by 3%(w/v)dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d.Concurrently,mice with colitis were administered 0.2 mL UCB(400μmol/L)by intra-gastric gavage for 7 d.Disease activity index(DAI)was monitored daily.Mice were sacrificed at the end of the experiment.The length of the colon and weight of the spleen were recorded.Serum level of D-lactate,intestinal digestive proteases activity,and changes to the gut flora were analyzed.In addition,colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.RESULTS Mice treated with UCB had significantly relieved severity of colitis,including lower DAI,longer colon length,and lower spleen weight(colon length:4.92±0.09 cm vs 3.9±0.15 cm;spleen weight:0.33±0.04 vs 0.74±0.04,P<0.001).UCB administration inactivated digestive proteases(chymotrypsin:18.70±0.69 U/g vs44.81±8.60 U/g;trypsin:1.52±0.23 U/g vs 9.05±1.77 U/g,P<0.01),increased expression of tight junction(0.99±0.05 vs 0.57±0.03,P<0.001),decreased serum level of D-lactate(31.76±3.37μmol/L vs 54.25±1.45μmol/L,P<0.001),and lowered histopathological score(4±0.57 vs 7±0.57,P<0.001)and activity of myeloperoxidase(46.79±2.57 U/g vs 110.32±19.19 U/g,P<0.001).UCB also regulated the intestinal microbiota,inhibited expression of tumor necrosis factor(TNF)αand interleukin 1β(TNF-α:52.61±7.81 pg/mg vs 105.04±11.92 pg/mg,interleukin 1β:13.43±1.68 vs 32.41±4.62 pg/mg,P<0.001),decreased expression of Toll-like receptor 4(0.61±0.09 vs 1.07±0.03,P<0.001)and myeloid differentiation primary response gene 88(0.73±0.08 vs 1.01±0.07,P<0.05),and increased expression of TNF-receptor-associated factor 6(0.79±0.02 vs0.43±0.09 P<0.05)and inhibitor of kappa Bα(0.93±0.07 vs 0.72±0.07,P<0.05)in the colon.CONCLUSION UCB can protect intestinal barrier function,regulate normal intestinal homeostasis,and suppress inflammation via the Toll-like receptor 4/nuclear factor-κB signaling pathway.
文摘AIM： To evaluate the effects of combined treatment of glutamine （Gln） and recombinant human growth hormone（rhGH） on intestinal barrier function following portal hypertension surgery. METHODS： This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups： control group （n = 20） and supplemental group （adding Gin and rhGH, n = 22）. Every patient received isocaloric and isonitrogenous standard total parenteral nutrition （TPN） starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein （CRP） levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS： On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group （33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, （1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively）, whereas the increase in serum TNF-α concentration was significantly reduced （41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05）. The increase in L/M ratio was significantly lower in the supplemental group than in the control group （0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05）. Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION： Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.
