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
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
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
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
Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier...Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.Methods:The Sprague-Dawley rats were randomly divided into three groups:control group,model group and JHD group.They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol(model group,n=10;JHD group,n=10)or isocaloric maltose dextrin(control group,n=10)for 6 weeks.After 3 weeks of feeding,the mice in the JHD group were given JHD(10 mL/kg/day)by gavage for 3 weeks,and those in the control and model groups received equal amounts of double-distilled water for the same period of time.Afterwards,all the rats were given lipopolysaccharide(LPS)by gavage and sacrificed 3.5 h later.LPS levels were measured in the portal blood to evaluate gut leakage.Transmission electron microscopy(TEM)was used to observe ultrastructural changes in the intestinal tract.Adherens junction(AJ)and tight junction(TJ)proteins were detected by Western blotting,immunofluorescence or immunohistochemistry.Results:JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis,inflammation and LPS expression.It improved pathological changes in the liver and alleviated intestinal ultrastructure injury.Moreover,it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens‐1(ZO-1)and occludin.It suppressed the activation of myosin light chain(MLC)phosphorylation.Conclusion:JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.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
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
BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the e...BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.展开更多
BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestina...BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.展开更多
Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modu...Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice.However,the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.Methods:The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms.In vivo,72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight,and piglets were fed the basal diet with 0(control,CON)and 200 mg/kg TUDCA for 30 d,respectively.Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected.In vitro,IPEC-J2 cells were subjected to 100μmol/L TUDCA to explore the possible underlying mechanisms.Results:Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets,possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity.In addition,TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria,which might contribute to the improved intestinal barrier function.Furthermore,the in-vitro results showed that TUDCA improved the E.coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5(TGR5)protein expression.However,knockdown of TGR5 and inhibition of myosin light chain kinase(MLCK)pathway abolished the TUDCA-improved epithelial barrier impairment in E.coli-treated IPEC-J2 cells,indicating the involvement of TGR5-MLCK in this process.Conclusions:These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets,suggesting the potential application of TUDCA in improving gut health in piglet production.展开更多
AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS S...AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.展开更多
OBJECTIVE:To evaluate the effects and related mechanisms of electroacupuncture(EA)on irritable bowel syndrome(IBS).METHODS:Male C57BL/6 mice were randomly allocated into normal,model,and EA groups.Experimental IBS mic...OBJECTIVE:To evaluate the effects and related mechanisms of electroacupuncture(EA)on irritable bowel syndrome(IBS).METHODS:Male C57BL/6 mice were randomly allocated into normal,model,and EA groups.Experimental IBS mice models were established by exposure to water avoidance stress(WAS).Mice in the EA group were treated with EA at bilateral Tianshu(ST 25)and Zusanli(ST 36)for 7 consecutive days,15 min each day.Abdominal withdrawal reflex(AWR)tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice.Expression levels of tight junction proteins(TJPs)and inflammatory cytokines in colon tissues were determined through immunofluorescence,real-time polymerase chain reactions(PCR)and Western blot assays.RESULTS:EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice.Moreover,EA promoted the expression of zonula occludens(ZO)-1,claudin-1,and occludin while suppressing the expression of interleukin(IL)-8,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αin water avoidance stress(WAS)-induced irritable bowel syndrome(IBS)mice.CONCLUSION:EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.展开更多
Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergist...Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergistic effects on gut health is still limited.In this study,alginate oligosaccharide(AOS)and cyanidin-3-O-glucoside(C3G)were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol,respectively,to study their effects on intestinal health.The results show that,in comparison to their individual applications,the combination of AOS and C3G(mass ratio,3:1)displayed a stronger ability to up-regulate the expression of tight junction proteins,while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 andβ-defensins were simultaneously increased in the intestinal mucus.Interestingly,the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS+C3G mixture.In addition,the AOS+C3G mixture was found to be more conducive to the positive transformation of intestinal flora,which stimulated the growth of beneficial bacteria Akkermansia,Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter.The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.展开更多
The intestinal epithelium is a single cell layer that forms the largest and most important barrier against the external environment. A proper functioning of the intestinal barrier is essential for maintaining optimal ...The intestinal epithelium is a single cell layer that forms the largest and most important barrier against the external environment. A proper functioning of the intestinal barrier is essential for maintaining optimal health. A disrupted intestinal barrier function has been associated with the development of autoimmune and inflammatory diseases. Probiotics are live microorganisms that confer a health benefit to the host and have been associated with prevention of diseases such as antibiotic-associated diarrhea, irritable bowel syndrome and inflammatory bowel disease. Probiotics can improve and restore the intestinal barrier function in diverse ways and effects are thought to be species- and even strain-specific. With this research the influence of probiotic bacteria in Ecologic? BARRIER on parameters of intestinal barrier function was investigated. The results show that each bacterial strain in Ecologic?BARRIER is in vitro capable to improve the epithelial barrier in diverse ways.展开更多
This research explored the protective impact of bamboo leaf flavonoids(BLF) in diquat(DQ) stressed broilers;providing insight of antioxidant, immune response and intestinal barrier function. This experiment consisted ...This research explored the protective impact of bamboo leaf flavonoids(BLF) in diquat(DQ) stressed broilers;providing insight of antioxidant, immune response and intestinal barrier function. This experiment consisted of two parts. In the first, 240 chicks were allotted to 2 groups with 8 replicates and15 chicks per replicate. Treatments consisted of a basic feed(control group, CON) and the basic feed plus1000 mg/kg BLF(BLF group, BLF) for 28 d, respectively. Then, following the conclusion of the first part, 16healthy broilers were selected from the CON group and the BLF group. They formed the second part of the experiment, and were allotted to 4 treatments with 8 broilers each: CON-no stress(CON-NS) group,CON-DQ group, BLF-NS group and the BLF-DQ group. Broilers were separately injected intraperitoneally with DQ solution at 40 mg/kg body weight or the same dose of phosphate buffer saline. The results revealed adding BLF to diet reduced the ratio of feed to weight gain of broilers compared to the basic feed group(P = 0.021). In comparison to the CON-NS group, BLF improved the levels of serum and jejunal mucosa total antioxidant capacity, immunoglobulin M, serum catalase, immunoglobulin A, interleukin10, jejunal mucosa interleukin 4, cecal butyric acid, valeric acid, isobutyric acid, isovaleric acid, upregulated zonula occludens-1(ZO-1), occludin(OCLN) and claudin-1(CLDN1) expressions, and reduced the levels of jejunal mucosa malondialdehyde(MDA), interleukin 1β, interleukin 6 and serum diamine oxidase(P < 0.05). Diquat stress elevated the contents of serum MDA, D-lactate, jejunal mucosa tumor necrosis factor a, reactive oxygen species and unclassified_f_Lachnospiraceae relative abundance, downregulated ZO-1, OCLN and CLDN1 expressions, and reduced Sobs, Chao and Ace indices(P < 0.05).Compared with CON-NS group, the concentration of isovaleric acid in the BLF-DQ group was higher(P < 0.05). In conclusion, by establishing a DQ stress injury model, it was elucidated that BLF may enhance antioxidant capacity, strengthen immunity, regulate volatile fatty acid contents, improve intestinal morphology, microbiota and other intestinal barrier functions, so as to mitigate the injury induced by oxidative stress in broilers.展开更多
This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning...This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods.Taoyuan black(TB),Xiangcun black(XB),and Duroc(DR)piglets(10 litters per breed;half male and half female)were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1,10,21(weaned),and 24(3 d after weaning)d old.The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement.D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P<0.01)than that of DR piglets,as well as the ileal diamine oxidase level at 1 d old.The expression level of mucin 1 was higher(P<0.05)in the ileum of TB and XB piglets than that of DR piglets,and it was the highest in the ileum of TB piglets at 21 d old.The expression levels of mucin 2 and mucin 13 were higher(P<0.10)in TB and XB piglets than those of DR piglets at 21 d old,whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P<0.05)than those of DR piglets at 24 d old.TB and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old,but they had higher Streptococcus at 1 and 24 d old than DR piglets(P<0.01).Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation,steroid biosynthesis,and bile acid synthesis.Collectively,these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function.Compared with DR piglets,TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning.Moreover,intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.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
AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
Background Lactulose as an effective prebiotic protects intestinal mucosal injury.Bacillus coagulans is widely used in feed additives because of its ability to promote intestinal health.Our previous study suggests tha...Background Lactulose as an effective prebiotic protects intestinal mucosal injury.Bacillus coagulans is widely used in feed additives because of its ability to promote intestinal health.Our previous study suggests that the combination of lactulose and Bacillus coagulans may be a good candidate as alternative for antibiotic growth promoters.However,the in vivo effects of lactulose and Bacillus coagulans on growth and intestinal health under immune challenge in piglets remains unclear.The objective of this study is to explore the protective effects of synbiotic containing lactu-lose and Bacillus coagulans on the intestinal mucosal injury and barrier dysfunction under immune challenge in weaned piglets.Methods Twenty four weaned piglets were assigned to 4 groups.Piglets in the CON-_(saline)and LPS-_(LPS)group were fed the basal diet,while others were fed either with chlortetracycline(CTC)or synbiotic mixture of lactulose and Bacillus coagulans for 32 d before injection of saline or lipopolysaccharide(LPS).Piglets were sacrificed 4 h after LPS injection to collect samples to determine intestinal morphology,integrity and barrier functions as well as relative genes and proteins.Results Our data showed that no differences were observed in the growth performance of the four test groups.LPS injection induced higher serum diamine oxidase activities,D-lactic acid levels,and endotoxin status,lower villus height and ratio of villus height to crypt depth,greater mRNA and lower protein expression related tight junction in both jejunum and ileum.In addition,a higher apoptosis index,and protein expression of Bax and caspase-3 were also observed in the LPS challenge group.Interestingly,dietary synbiotic mixture with lactulose and Bacillus coagulans protected against LPS-induced intestinal damage,barrier dysfunction and higher apoptosis as well as CTC.Conclusions Our data suggest that dietary supplementation of synbiotic mixture with lactulose and Bacillus coagu-lans showed resilience to LPS-induced intestinal morphological damage,barrier dysfunction and aggressive apoptosis in piglets as well as the protective effects of CTC.These results indicate that synbiotic mixture of lactulose and Bacillus coagulans showed beneficial effects on performance and resilience to acute immune stress in weaned piglets.展开更多
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 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 National Natural Science Foundation of China(No.30801536).
文摘Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.Methods:The Sprague-Dawley rats were randomly divided into three groups:control group,model group and JHD group.They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol(model group,n=10;JHD group,n=10)or isocaloric maltose dextrin(control group,n=10)for 6 weeks.After 3 weeks of feeding,the mice in the JHD group were given JHD(10 mL/kg/day)by gavage for 3 weeks,and those in the control and model groups received equal amounts of double-distilled water for the same period of time.Afterwards,all the rats were given lipopolysaccharide(LPS)by gavage and sacrificed 3.5 h later.LPS levels were measured in the portal blood to evaluate gut leakage.Transmission electron microscopy(TEM)was used to observe ultrastructural changes in the intestinal tract.Adherens junction(AJ)and tight junction(TJ)proteins were detected by Western blotting,immunofluorescence or immunohistochemistry.Results:JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis,inflammation and LPS expression.It improved pathological changes in the liver and alleviated intestinal ultrastructure injury.Moreover,it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens‐1(ZO-1)and occludin.It suppressed the activation of myosin light chain(MLC)phosphorylation.Conclusion:JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.
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.
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.
基金supported by grants from the National Basic Research Program (973) of China (2007CB513005, 2009CB522406)a Research Grant awarded by the Health Bureau Fund ofZhejiang Province (2007QN006, 2008A050)
文摘BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.
基金supported by grants from the National Basic Research Program(973)of China(2007CB513005 and 2009CB522406)the Health Bureau Fund of Zhejiang Province(2008A050)
文摘BACKGROUND:Most patients after liver transplantation (LT) suffer from intestinal barrier dysfunction.Glycyl-glutamine (Gly-Gln) by parenteral supplementation is hydrolyzed to release glutamine,which improves intestinal barrier function in intestinal injury.This study aimed to investigate the effect of GlyGln by enteral supplementation on intestinal barrier function in rats after allogenetic LT under immunosuppressive therapy.METHODS:Twelve inbred Lewis rats were selected randomly as donors,and 24 inbred Brown Norway (BN) rats as recipients of allogenetic LT.The recipients were divided into a control group (Ala,n=12) and an experimental group (Gly-Gln,n=12).In each group,6 normal BN rats were sampled for normal parameters on preoperative day 3.The 6 recipients in the control group received alanine (Ala) daily by gastric perfusion for 3 preoperative days and 7 postoperative days,and the 6 recipients in the experimental group were given Gly-Gln in the same manner.The 12 BN recipients underwent orthotopic LT under sterile conditions after a 3-day fast and were given immunosuppressive therapy for 7 days.They were harvested for sampling on postoperative day 8.The following parameters were assessed:intestinal mucosal protein content,mucosal ultrastructure,ileocecal sIgA content,portal plasma levels of endotoxin and TNF-α,and bacterial translocation.RESULTS:All recipients were alive after LT.On preoperative day 3,all parameters were similar in the two groups.On postoperative day 8,all parameters in the two groups were remarkably changed from those on preoperative day 3.However,compared to the Ala group,supplementation withGly-Gln increased the levels of intestinal mucosal protein and ileocecal sIgA,improved mucosal microvilli,and decreased portal plasma levels of endotoxin and TNF-α as well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.
基金supported by the National Natural Science Foundation of China(31972636,31672508,31790411 and 31802103)the National Key Research and Development Program of China(2017YFD0500501)+1 种基金the Guangdong Key Areas Research and Development Project(2019B020218001)the Provincial Agricultural Science and Technology Innovation Promotion and Agricultural Resources and Ecological Environmental Protection Construction Project(2021KJ266).
文摘Background:Tauroursodeoxycholic acid(TUDCA),a hydrophilic bile acid,is the main medicinal component of bear bile and is commonly used to treat a variety of hepatobiliary diseases.Meanwhile,TUDCA has been shown to modulate the intestinal barrier function and alleviate DSS-induced colitis in mice.However,the effect of TUDCA on the intestinal barrier of weaned piglets remains largely unclear.Methods:The weaned piglets and porcine IPEC-J2 intestinal epithelial cells were used to investigate the effects of TUDCA on intestinal barrier function in weaned piglets and explore the possible underlying mechanisms.In vivo,72 healthy weaned piglets were randomly allocated into 2 groups according to their gender and body weight,and piglets were fed the basal diet with 0(control,CON)and 200 mg/kg TUDCA for 30 d,respectively.Three female and three male piglets reflecting the average bodyweight were slaughtered in each group and samples were collected.In vitro,IPEC-J2 cells were subjected to 100μmol/L TUDCA to explore the possible underlying mechanisms.Results:Our results demonstrated that dietary TUDCA supplementation significantly reduced the diarrhea incidence of weaned piglets,possibly attributing to the TUDCA-enhanced intestinal barrier function and immunity.In addition,TUDCA supplementation altered serum metabolites and the relative abundance of certain gut bacteria,which might contribute to the improved intestinal barrier function.Furthermore,the in-vitro results showed that TUDCA improved the E.coli-induced epithelial barrier impairment of IPEC-J2 cells and increased Takeda G-coupled protein receptor 5(TGR5)protein expression.However,knockdown of TGR5 and inhibition of myosin light chain kinase(MLCK)pathway abolished the TUDCA-improved epithelial barrier impairment in E.coli-treated IPEC-J2 cells,indicating the involvement of TGR5-MLCK in this process.Conclusions:These findings showed that TUDCA improved intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets,suggesting the potential application of TUDCA in improving gut health in piglet production.
基金Supported by Medjaden Academy and Research Foundation for Young Scientists,No.MJA20170410
文摘AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.
基金Supported by the Research and Practice Innovation Program for Postgraduates of Jiangsu Province(Mechanism of Electroacupuncture Regulating Bile Acid Receptor to Alleviate Visceral Hypersensitivity in Irritable Bowel Syndrome,No.KYCX20_1469)the National Natural Science Fund(Mechanism of Electroacupuncture Regulating CRF-NLRP6 Inflammasome-Related Pathways in Intestinal Flora Immune Dialogue,No.81804193)+1 种基金the Leading Talents Project of Jiangsu Provincial Administration of TCM(Clinical Effect and Mechanism of Acupuncture and Moxibustion on Irritable Bowel Syndrome,No.SLJ0206)the Peak Talent Project of Jiangsu Province Hospital of TCM(Clinical Effect and Mechanism of Acupuncture and Moxibustion in the Treatment of Functional Gastrointestinal Diseases,No.y2018rc05)。
文摘OBJECTIVE:To evaluate the effects and related mechanisms of electroacupuncture(EA)on irritable bowel syndrome(IBS).METHODS:Male C57BL/6 mice were randomly allocated into normal,model,and EA groups.Experimental IBS mice models were established by exposure to water avoidance stress(WAS).Mice in the EA group were treated with EA at bilateral Tianshu(ST 25)and Zusanli(ST 36)for 7 consecutive days,15 min each day.Abdominal withdrawal reflex(AWR)tests and intestinal motility tests were performed to evaluate visceral sensitivity and intestinal motility of mice.Expression levels of tight junction proteins(TJPs)and inflammatory cytokines in colon tissues were determined through immunofluorescence,real-time polymerase chain reactions(PCR)and Western blot assays.RESULTS:EA alleviated visceral hypersensitivity and intestinal hypermotility in WAS-induced IBS mice.Moreover,EA promoted the expression of zonula occludens(ZO)-1,claudin-1,and occludin while suppressing the expression of interleukin(IL)-8,interferon(IFN)-γ,and tumor necrosis factor(TNF)-αin water avoidance stress(WAS)-induced irritable bowel syndrome(IBS)mice.CONCLUSION:EA alleviated WAS-induced IBS in mice by promoting intestinal barrier functions and suppressing the expression of inflammatory cytokines.
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)Fujian Science Foundation for Distinguished Young Scholars(2020J06024).
文摘Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergistic effects on gut health is still limited.In this study,alginate oligosaccharide(AOS)and cyanidin-3-O-glucoside(C3G)were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol,respectively,to study their effects on intestinal health.The results show that,in comparison to their individual applications,the combination of AOS and C3G(mass ratio,3:1)displayed a stronger ability to up-regulate the expression of tight junction proteins,while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 andβ-defensins were simultaneously increased in the intestinal mucus.Interestingly,the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS+C3G mixture.In addition,the AOS+C3G mixture was found to be more conducive to the positive transformation of intestinal flora,which stimulated the growth of beneficial bacteria Akkermansia,Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter.The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.
文摘The intestinal epithelium is a single cell layer that forms the largest and most important barrier against the external environment. A proper functioning of the intestinal barrier is essential for maintaining optimal health. A disrupted intestinal barrier function has been associated with the development of autoimmune and inflammatory diseases. Probiotics are live microorganisms that confer a health benefit to the host and have been associated with prevention of diseases such as antibiotic-associated diarrhea, irritable bowel syndrome and inflammatory bowel disease. Probiotics can improve and restore the intestinal barrier function in diverse ways and effects are thought to be species- and even strain-specific. With this research the influence of probiotic bacteria in Ecologic? BARRIER on parameters of intestinal barrier function was investigated. The results show that each bacterial strain in Ecologic?BARRIER is in vitro capable to improve the epithelial barrier in diverse ways.
基金supported by Zhejiang Provincial Key R&D Program of China(2022C02059)Zhejiang Provincial Key Agricultural Research Institute of Green Animal Health Products Project(2021Y30004).
文摘This research explored the protective impact of bamboo leaf flavonoids(BLF) in diquat(DQ) stressed broilers;providing insight of antioxidant, immune response and intestinal barrier function. This experiment consisted of two parts. In the first, 240 chicks were allotted to 2 groups with 8 replicates and15 chicks per replicate. Treatments consisted of a basic feed(control group, CON) and the basic feed plus1000 mg/kg BLF(BLF group, BLF) for 28 d, respectively. Then, following the conclusion of the first part, 16healthy broilers were selected from the CON group and the BLF group. They formed the second part of the experiment, and were allotted to 4 treatments with 8 broilers each: CON-no stress(CON-NS) group,CON-DQ group, BLF-NS group and the BLF-DQ group. Broilers were separately injected intraperitoneally with DQ solution at 40 mg/kg body weight or the same dose of phosphate buffer saline. The results revealed adding BLF to diet reduced the ratio of feed to weight gain of broilers compared to the basic feed group(P = 0.021). In comparison to the CON-NS group, BLF improved the levels of serum and jejunal mucosa total antioxidant capacity, immunoglobulin M, serum catalase, immunoglobulin A, interleukin10, jejunal mucosa interleukin 4, cecal butyric acid, valeric acid, isobutyric acid, isovaleric acid, upregulated zonula occludens-1(ZO-1), occludin(OCLN) and claudin-1(CLDN1) expressions, and reduced the levels of jejunal mucosa malondialdehyde(MDA), interleukin 1β, interleukin 6 and serum diamine oxidase(P < 0.05). Diquat stress elevated the contents of serum MDA, D-lactate, jejunal mucosa tumor necrosis factor a, reactive oxygen species and unclassified_f_Lachnospiraceae relative abundance, downregulated ZO-1, OCLN and CLDN1 expressions, and reduced Sobs, Chao and Ace indices(P < 0.05).Compared with CON-NS group, the concentration of isovaleric acid in the BLF-DQ group was higher(P < 0.05). In conclusion, by establishing a DQ stress injury model, it was elucidated that BLF may enhance antioxidant capacity, strengthen immunity, regulate volatile fatty acid contents, improve intestinal morphology, microbiota and other intestinal barrier functions, so as to mitigate the injury induced by oxidative stress in broilers.
基金supported by the Key Project of Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(U20A2056)Youth Foundation of Guangxi Natural Science Foundation(2021JJB130431)+1 种基金Open Foundation of the Key Laboratory of Agro-Ecological Processes in Subtropical Region of Chinese Academy of Sciences(ISA2022105)Special Funds for Construction of Innovative Provinces in Hunan Province(2019RS3022)
文摘This study explored the developmental changes in small intestinal barrier function and the potential regulatory roles of intestinal microbiota and metabolites in different breeds of piglets during suckling and weaning periods.Taoyuan black(TB),Xiangcun black(XB),and Duroc(DR)piglets(10 litters per breed;half male and half female)were selected for sampling to evaluate the intestinal barrier-related indexes and intestinal microbiota and metabolites at 1,10,21(weaned),and 24(3 d after weaning)d old.The results showed that weaning led to severe shedding of small intestinal microvilli and sparse microvilli arrangement.D-lactate level in the ileum of TB and XB piglets during suckling and weaning periods was lower(P<0.01)than that of DR piglets,as well as the ileal diamine oxidase level at 1 d old.The expression level of mucin 1 was higher(P<0.05)in the ileum of TB and XB piglets than that of DR piglets,and it was the highest in the ileum of TB piglets at 21 d old.The expression levels of mucin 2 and mucin 13 were higher(P<0.10)in TB and XB piglets than those of DR piglets at 21 d old,whereas mucin2 and mucin 13 in the ileum of TB and XB piglets were higher(P<0.05)than those of DR piglets at 24 d old.TB and XB piglets had a lower relative abundance of Escherichia_Shigella at 21 and 24 d old,but they had higher Streptococcus at 1 and 24 d old than DR piglets(P<0.01).Differential metabolites between the three breeds of piglets were mainly related to oxidative phosphorylation,steroid biosynthesis,and bile acid synthesis.Collectively,these findings suggest that different pig breeds present differences in the development of the small intestinal barrier function.Compared with DR piglets,TB and XB piglets had higher intestinal permeability during the suckling period and a stronger intestinal mechanical barrier after weaning.Moreover,intestinal microbiota and metabolites are the key factors for developing small intestinal barrier functions in different breeds of piglets.
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 Key Projects of China,No.81230057National Natural Science Foundation of China,No.81172325The Major Basic Research Program of Shanghai,No.12DZ1930502
文摘AIM: To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
基金supported by the National Key R&D Program of China(2017YFE0114400).
文摘Background Lactulose as an effective prebiotic protects intestinal mucosal injury.Bacillus coagulans is widely used in feed additives because of its ability to promote intestinal health.Our previous study suggests that the combination of lactulose and Bacillus coagulans may be a good candidate as alternative for antibiotic growth promoters.However,the in vivo effects of lactulose and Bacillus coagulans on growth and intestinal health under immune challenge in piglets remains unclear.The objective of this study is to explore the protective effects of synbiotic containing lactu-lose and Bacillus coagulans on the intestinal mucosal injury and barrier dysfunction under immune challenge in weaned piglets.Methods Twenty four weaned piglets were assigned to 4 groups.Piglets in the CON-_(saline)and LPS-_(LPS)group were fed the basal diet,while others were fed either with chlortetracycline(CTC)or synbiotic mixture of lactulose and Bacillus coagulans for 32 d before injection of saline or lipopolysaccharide(LPS).Piglets were sacrificed 4 h after LPS injection to collect samples to determine intestinal morphology,integrity and barrier functions as well as relative genes and proteins.Results Our data showed that no differences were observed in the growth performance of the four test groups.LPS injection induced higher serum diamine oxidase activities,D-lactic acid levels,and endotoxin status,lower villus height and ratio of villus height to crypt depth,greater mRNA and lower protein expression related tight junction in both jejunum and ileum.In addition,a higher apoptosis index,and protein expression of Bax and caspase-3 were also observed in the LPS challenge group.Interestingly,dietary synbiotic mixture with lactulose and Bacillus coagulans protected against LPS-induced intestinal damage,barrier dysfunction and higher apoptosis as well as CTC.Conclusions Our data suggest that dietary supplementation of synbiotic mixture with lactulose and Bacillus coagu-lans showed resilience to LPS-induced intestinal morphological damage,barrier dysfunction and aggressive apoptosis in piglets as well as the protective effects of CTC.These results indicate that synbiotic mixture of lactulose and Bacillus coagulans showed beneficial effects on performance and resilience to acute immune stress in weaned piglets.
