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
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
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
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
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
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
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
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
Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrati...Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.展开更多
Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investig...Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.展开更多
Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long...Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.展开更多
Fasting is typically used before feeding metabolizable energy assessment in broilers.Previous studies have shown that fasting cause atrophy of the intestinal villus.Whether fasting affects intestinal permeability duri...Fasting is typically used before feeding metabolizable energy assessment in broilers.Previous studies have shown that fasting cause atrophy of the intestinal villus.Whether fasting affects intestinal permeability during refeeding by altering barrier function and nutrient absorption is of concern.Here,23-d-old broilers were randomly assigned to 5 treatments,fasted for 0,12,24,36,and 48 h,respectively,and then refed for 2 d,to study the impact of different duration of fasting on the intestinal regeneration and barrier function during refeeding.Results showed that the intestinal morphology in fasted birds was recovered in 2 d of refeeding at most.As fasting durations increased,enterocytes per intestinal villus were linearly and quadratically increased(both P<0.05),whereas goblet cells per intestinal villus was linearly decreased(both P<0.05).Besides,the mRNA level of lysozyme was linearly decreased as fasting durations increased during refeeding(both P<0.05),while quadratically increased mucin 2 was observed only after 1 d of refeeding(P<0.05).Linear increase effects were observed for claudin 2 and zonula occludens-1with increased fasting durations after 1 d of refeeding(all P<0.05),and linear and quadratical effects were observed for claudin 2 at 2 d of refeeding(both P<0.05).Besides,we found that intestinal permeability to creatinine,4 and 70 kD dextran were linearly and quadratically decreased with increased fasting durations at 6 h and 1 d of refeeding(all P<0.05).Furthermore,jejunum proteomic from birds refed for 6 h showed that birds fasted for 36 h showed increased antimicrobial peptides and upregulated retinol metabolism when compared to the nonfasted birds(P<0.05).Further study showed that retinyl ester catabolism was inhibited during fasting and enhanced during refeeding.Results of intestinal organoid culture showed that retinol benefits the cell proliferation and enterocyte differentiation.In conclusion,the intestinal permeability to small and large molecules was decreased during refeeding by strengthening the intestinal barrier function,and the activated retinol metabolism during refeeding is involved in the intestinal regeneration and strengthens the intestinal barrier.展开更多
Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the ...Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.展开更多
Background Zinc glycine chelate(Zn-Gly)has anti-inflammation and growth-promoting properties;however,the mechanism of Zn-Gly contribution to gut barrier function in Cherry Valley ducks during intestinal inflammation i...Background Zinc glycine chelate(Zn-Gly)has anti-inflammation and growth-promoting properties;however,the mechanism of Zn-Gly contribution to gut barrier function in Cherry Valley ducks during intestinal inflammation is unknown.Three-hundred 1-day-old ducks were divided into 5 groups(6 replicates and 10 ducks per replicate)in a completely randomized design:the control and dextran sulfate sodium(DSS)groups were fed a corn-soybean meal basal diet,and experimental groups received supplements of 70,120 or 170 mg/kg Zn in form of Zn-Gly.The DSS and treatment groups were given 2 mL of 0.45 g/mL DSS daily during d 15–21,and the control group received normal saline.The experiment lasted 21 d.Results Compared with DSS group,70,120 and 170 mg/kg Zn significantly increased body weight(BW),villus height and the ratio of villus to crypt,and significantly decreased the crypt depth of jejunum at 21 d.The number of goblet cells in jejunal villi in the Zn-Gly group was significantly increased by periodic acid-Schiff staining.Compared with control,the content of intestinal permeability marker D-lactic acid(D-LA)and fluxes of fluorescein isothiocyanate(FITC-D)in plasma of DSS group significantly increased,and 170 mg/kg Zn supplementation significantly decreased the D-LA content and FITC-D fluxes.Compared with control,contents of plasma,jejunum endotoxin and jejunum pro-inflammatory factors IL-1β,IL-6 and TNF-αwere significantly increased in DSS group,and were significantly decreased by 170 mg/kg Zn supplementation.Dietary Zn significantly increased the contents of anti-inflammatory factors IL-10,IL-22 and sIgA and IgG in jejunum.Real-time PCR and Western blot results showed that 170 mg/kg Zn supplementation significantly increased mRNA expression levels of CLDN-1 and expression of OCLN protein in jejunum,and decreased gene and protein expression of CLDN-2 compared with DSS group.The 120 mg/kg Zn significantly promoted the expressions of IL-22 and IgA.Dietary Zn-Gly supplementation significantly decreased pro-inflammatory genes IL-8 and TNF-αexpression levels and TNF-αprotein expression in jejunum.Additionally,Zn significantly reduced the gene and protein expression of TLR4,MYD88 and NF-κB p65.Conclusions Zn-Gly improved duck BW and alleviated intestinal injury by regulating intestinal morphology,barrier function and gut inflammation-related signal pathways TLR4/MYD88/NF-κB p65.展开更多
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 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,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 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 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funded by the National Natural Science Foundation of China(32273074,31972746,31872538 and 31772809)the Basic Scientific Research Project of Liaoning Provincial Department of Education,China(LJKZ0632)。
文摘Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.
基金supported by fund from the National Natural Science Foundation of China (32172322)Shandong Provincial Natural Science Foundation (ZR2023QC291)Shandong Traditional Chinese Medicine Technology Project (Q-2023130)。
文摘Previous studies have shown that trans fatty acids(TFA) are associated with several chronic diseases,the gut microbiota is directly influenced by dietary components and linked to chronic diseases.Our research investigated the effects of elaidic acid(EA),a typical TFA,on the gut microbiota to understand the underlying mechanisms of TFA-related chronic diseases.16S rDNA gene sequencing on faecal samples from Sprague-Dawley rats were performed to explore the composition change of the gut microbiota by EA gavage for 4 weeks.The results showed that the intake of EA increased the abundance of well-documented harmful bacteria,such as Proteobacteria,Anaerotruncus,Oscillibacter and Desulfovibrionaceae.Plus,EA induced translocation of lipopolysaccharides(LPS) and the above pathogenic bacteria,disrupted the intestinal barrier,led to gut-liver axis derangement and TLR4 pathway activation in the liver.Overall,EA induced intestinal barrier damage and regulated TLR4-MyD88-NF-κB/MAPK pathways in the liver of SD rats,leading to the activation of NLRP3 inflammasome and inflammatory liver damage.
基金supported by the National Natural Science Foundation of China(32272916)National key Research&Development Program of China(2023YFD1301400)+1 种基金the Program for Shaanxi Science&Technology from Shaanxi Provincial Science and Technology Department(2022GDTSLD-46-0302,2023KXJ-243,2023GXJS-02-01,K3031223075,L2022-QCYZXNY-004,2021TD-30,019HBGC-16,2019ZDXM3-02)the Yongjiang Innovative Research Team。
文摘Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.
基金supported by the funding of the National Natural Science Foundation of China(32072752)the Southwest Minzu University Double World-Class Project,China(XM2023011)。
文摘Fasting is typically used before feeding metabolizable energy assessment in broilers.Previous studies have shown that fasting cause atrophy of the intestinal villus.Whether fasting affects intestinal permeability during refeeding by altering barrier function and nutrient absorption is of concern.Here,23-d-old broilers were randomly assigned to 5 treatments,fasted for 0,12,24,36,and 48 h,respectively,and then refed for 2 d,to study the impact of different duration of fasting on the intestinal regeneration and barrier function during refeeding.Results showed that the intestinal morphology in fasted birds was recovered in 2 d of refeeding at most.As fasting durations increased,enterocytes per intestinal villus were linearly and quadratically increased(both P<0.05),whereas goblet cells per intestinal villus was linearly decreased(both P<0.05).Besides,the mRNA level of lysozyme was linearly decreased as fasting durations increased during refeeding(both P<0.05),while quadratically increased mucin 2 was observed only after 1 d of refeeding(P<0.05).Linear increase effects were observed for claudin 2 and zonula occludens-1with increased fasting durations after 1 d of refeeding(all P<0.05),and linear and quadratical effects were observed for claudin 2 at 2 d of refeeding(both P<0.05).Besides,we found that intestinal permeability to creatinine,4 and 70 kD dextran were linearly and quadratically decreased with increased fasting durations at 6 h and 1 d of refeeding(all P<0.05).Furthermore,jejunum proteomic from birds refed for 6 h showed that birds fasted for 36 h showed increased antimicrobial peptides and upregulated retinol metabolism when compared to the nonfasted birds(P<0.05).Further study showed that retinyl ester catabolism was inhibited during fasting and enhanced during refeeding.Results of intestinal organoid culture showed that retinol benefits the cell proliferation and enterocyte differentiation.In conclusion,the intestinal permeability to small and large molecules was decreased during refeeding by strengthening the intestinal barrier function,and the activated retinol metabolism during refeeding is involved in the intestinal regeneration and strengthens the intestinal barrier.
基金funded by the National Nature Science Foundation of China(32002196)。
文摘Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0060)。
文摘Background Zinc glycine chelate(Zn-Gly)has anti-inflammation and growth-promoting properties;however,the mechanism of Zn-Gly contribution to gut barrier function in Cherry Valley ducks during intestinal inflammation is unknown.Three-hundred 1-day-old ducks were divided into 5 groups(6 replicates and 10 ducks per replicate)in a completely randomized design:the control and dextran sulfate sodium(DSS)groups were fed a corn-soybean meal basal diet,and experimental groups received supplements of 70,120 or 170 mg/kg Zn in form of Zn-Gly.The DSS and treatment groups were given 2 mL of 0.45 g/mL DSS daily during d 15–21,and the control group received normal saline.The experiment lasted 21 d.Results Compared with DSS group,70,120 and 170 mg/kg Zn significantly increased body weight(BW),villus height and the ratio of villus to crypt,and significantly decreased the crypt depth of jejunum at 21 d.The number of goblet cells in jejunal villi in the Zn-Gly group was significantly increased by periodic acid-Schiff staining.Compared with control,the content of intestinal permeability marker D-lactic acid(D-LA)and fluxes of fluorescein isothiocyanate(FITC-D)in plasma of DSS group significantly increased,and 170 mg/kg Zn supplementation significantly decreased the D-LA content and FITC-D fluxes.Compared with control,contents of plasma,jejunum endotoxin and jejunum pro-inflammatory factors IL-1β,IL-6 and TNF-αwere significantly increased in DSS group,and were significantly decreased by 170 mg/kg Zn supplementation.Dietary Zn significantly increased the contents of anti-inflammatory factors IL-10,IL-22 and sIgA and IgG in jejunum.Real-time PCR and Western blot results showed that 170 mg/kg Zn supplementation significantly increased mRNA expression levels of CLDN-1 and expression of OCLN protein in jejunum,and decreased gene and protein expression of CLDN-2 compared with DSS group.The 120 mg/kg Zn significantly promoted the expressions of IL-22 and IgA.Dietary Zn-Gly supplementation significantly decreased pro-inflammatory genes IL-8 and TNF-αexpression levels and TNF-αprotein expression in jejunum.Additionally,Zn significantly reduced the gene and protein expression of TLR4,MYD88 and NF-κB p65.Conclusions Zn-Gly improved duck BW and alleviated intestinal injury by regulating intestinal morphology,barrier function and gut inflammation-related signal pathways TLR4/MYD88/NF-κB p65.
