BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore th...BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.展开更多
This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier...This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.展开更多
BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In Chin...BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.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
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 effe...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-αas 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+andγδTCR+lymphocytes.In contrast,compared to the control group,supplementation with probiotics reduced the levels of serum endotoxin,TNF-αand 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 intestinal ba...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-αas well as bacterial translocation.CONCLUSION:Enteral supplementation with Gly-Gln improved intestinal barrier function after allogenetic LT in rats.展开更多
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
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 the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.
Since ancient times,mulberry leaf has a prominent intestinal regulatory effect,and the close relationship between intestinal diseases and other diseases has attracted more and more attention.This article reviewed the ...Since ancient times,mulberry leaf has a prominent intestinal regulatory effect,and the close relationship between intestinal diseases and other diseases has attracted more and more attention.This article reviewed the relevant articles on the mulberry leaf in recent years and summarized the research progress of mulberry leaf‘s biological activities and their effects on human intestinal regulation and the corresponding mechanisms.Multiple components in the mulberry leaf can individually or synergistically affect the human intestine,directly and indirectly promote the digestion,absorption,and transport function of the small intestine,adjust the balance of the flora,enhance the barrier function of the intestinal mucosa,improve the immunity of the part,and facilitate the intestine recovery from illness.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
AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal g...AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.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
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
Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse eve...Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.展开更多
BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive...BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.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
BACKGROUND Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation.Oral probiotics are one of the postoperative treatments for rapid rehabilitation.However,there is a lack...BACKGROUND Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation.Oral probiotics are one of the postoperative treatments for rapid rehabilitation.However,there is a lack of prospective studies on this topic after appendectomy.AIM To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy.METHODS This was a prospective,randomized trial.A total of 60 emergency patients were randomly divided into a control group(n=30)and a probiotic group(n=30).Patients in the control group started to drink some water the first day after surgery,and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery.The indices of inflammation and postoperative conditions were recorded,and the data were analyzed with RStudio 4.3.2 software.RESULTS A total of 60 participants were included.Compared with those in the control group,the C-reactive protein(CRP),interleukin 6 and procalcitonin(PCT)levels were significantly lower in the probiotic group at 2 d after surgery(P=2.224e-05,P=0.037,and P=0.002,respectively,all P<0.05).This trend persisted at day 5 post-surgery,with CRP and PCT levels remaining significantly lower in the probiotic group(P=0.001 and P=0.043,both P<0.05).Furthermore,probiotics0.028,both P<0.05).CONCLUSION Postoperative oral administration of probiotics may modulate the gut microbiota,benefit the recovery of the early inflammatory response,and subsequently enhance recovery after appendectomy.展开更多
基金Supported by National Natural Science Foundation of China,No.82300739Hunan Provincial Natural Science Foundation,No.2023JJ40821Changsha Natural Science Foundation,No.kq2208308.
文摘BACKGROUND Intestinal barrier dysfunction is a prevalent and varied manifestation of acute pancreatitis(AP).Molecular mechanisms underlying the early intestinal barrier in AP remain poorly understood.AIM To explore the biological processes and mechanisms of intestinal injury associated with AP,and to find potential targets for early prevention or treatment of intestinal barrier injury.METHODS This study utilized single-cell RNA sequencing of the small intestine,alongside in vitro and in vivo experiments,to examine intestinal barrier function homeostasis during the early stages of AP and explore involved biological processes and potential mechanisms.RESULTS Seventeen major cell types and 33232 cells were identified across all samples,including normal,AP1(4x caerulein injections,animals sacrificed 2 h after the last injection),and AP2(8x caerulein injections,animals sacrificed 4 h after the last injection).An average of 980 genes per cell was found in the normal intestine,compared to 927 in the AP1 intestine and 1382 in the AP2 intestine.B cells,dendritic cells,mast cells(MCs),and monocytes in AP1 and AP2 showed reduced numbers compared to the normal intestine.Enterocytes,brush cells,enteroendocrine cells,and goblet cells maintained numbers similar to the normal intestine,while cytotoxic T cells and natural killer(NK)cells increased.Enterocytes in early AP exhibited elevated programmed cell death and intestinal barrier dysfunction but retained absorption capabilities.Cytotoxic T cells and NK cells showed enhanced pathogen-fighting abilities.Activated MCs,secreted chemokine(C-C motif)ligand 5(CCL5),promoted neutrophil and macrophage infiltration and contributed to barrier dysfunction.CONCLUSION These findings enrich our understanding of biological processes and mechanisms in AP-associated intestinal injury,suggesting that CCL5 from MCs is a potential target for addressing dysfunction.
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approved by the Institutional Animal Care and Use Committee of Cloud-Clone Corp Wuhan(protocol No.IACU23-1252,on November 29,2023).
文摘BACKGROUND Irritable bowel syndrome(IBS)is a complex bowel disorder marked by recurrent abdominal pain and irregular stools.The condition is persistent and significantly affects the quality of life of patients.In China,5.6%-11.5%of the population has IBS,with diarrheal IBS(IBS-D)comprising about 31.5%of the total.AIM To investigate how human umbilical cord mesenchymal stem cells(hUC-MSCs)can alleviate the symptoms with the help of an IBS-D rat model.METHODS Sixty specific pathogen-free-grade male Sprague-Dawley rats were acquired and divided into five groups:Control group,model group,and three hUC-MSC groups with different doses.The model group was induced using a combination of acetic acid and binding stress.We determined the body weight of the mice;analyzed their fecal characteristics,inflammatory factors,and intestinal tissue damage;and conducted intestinal flora analyses.RESULTS The results showed that hUC-MSCs observably restored the dramatic weight loss in the rat model and also lowered the fecal water content to some extent.In addition,hUC-MSCs reduced the expression of inflammatory factors to alleviate the inflammatory response and increased the expression of intestinal barrier functional proteins to restore the colon injury by colonizing the colon tissue.In addition,hUC-MSCs were able to maintain the abundance and diversity of gut flora.CONCLUSION Thus,hUC-MSCs can reduce the expression of inflammatory factors,improve the expression of intestinal barrier functional proteins,and maintain the abundance and diversity of intestinal flora in IBS-D by colonizing the colon tissue.
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 of Zhejiang 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-αas 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+andγδTCR+lymphocytes.In contrast,compared to the control group,supplementation with probiotics reduced the levels of serum endotoxin,TNF-αand 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-αas 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 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.
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 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The Key Generic Technology Research Project of High-Quality Agricultural Development of Hebei Province(Grant No.20327121D)Biomedical Development and Transformation Research Project of Hebei Province(Grant No.2020TXZH05)Science and Technology Research Project of Higher Education Institutions of Hebei Province(Grant No.2019188)。
文摘Since ancient times,mulberry leaf has a prominent intestinal regulatory effect,and the close relationship between intestinal diseases and other diseases has attracted more and more attention.This article reviewed the relevant articles on the mulberry leaf in recent years and summarized the research progress of mulberry leaf‘s biological activities and their effects on human intestinal regulation and the corresponding mechanisms.Multiple components in the mulberry leaf can individually or synergistically affect the human intestine,directly and indirectly promote the digestion,absorption,and transport function of the small intestine,adjust the balance of the flora,enhance the barrier function of the intestinal mucosa,improve the immunity of the part,and facilitate the intestine recovery from illness.
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 National Basic Research Program (973) of China, No. 2007CB513005, No. 2009CB522401 and No. 2009CB522406
文摘AIM: To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. METHODS: The whole experiment was divided into three groups: (1) Normal group (n = 12): normal BN rats without any drug or operation; (2) SGT group (syngeneic transplant of BN-BN, n = 12): both donors and recipients were BN rats; and (3) AGT group (allogeneic transplant of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one d after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. RESULTS: During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (aP < 0.01, bP < 0.001, respectively). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both aP < 0.01, bP < 0.05, respectively). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87± 0.13) were remarkably reduced (both aP < 0.01, bP < 0.05, respectively). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. CONCLUSION: Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.
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 grants from the National Research Foundation of Korea funded by the Korean government(No.2020R1A4A1018598,NRF-2021R1A2C2006818,2022M3A9B6017813 and NRF-2023R1A2C1006836).
文摘Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.
基金Supported by the Key-Area Research and Development Program of Guangdong Province,No.2022B1111070006the Guangdong Innovation Research Team for Higher Education,No.2021KCXTD025.
文摘BACKGROUND While colorectal polyps are not cancerous,some types of polyps,known as adenomas,can develop into colorectal cancer over time.Polyps can often be found and removed by colonoscopy;however,this is an invasive and expensive test.Thus,there is a need for new methods of screening patients at high risk of developing polyps.AIM To identify a potential association between colorectal polyps and small intestine bacteria overgrowth(SIBO)or other relevant factors in a patient cohort with lactulose breath test(LBT)results.METHODS A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology.SIBO was diagnosed by measuring LBTderived hydrogen(H)and methane(M)levels according to 2017 North American Consensus recommendations.Logistic regression was used to assess the ability of LBT to predict colorectal polyps.Intestinal barrier function damage(IBFD)was determined by blood assays.RESULTS H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group(41%vs 23%,P<0.01;71%vs 59%,P<0.05,respectively).Within 90 min of lactulose ingestion,the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group(P<0.01,and P=0.03,respectively).In 227 patients with SIBO defined by combining H and M values,the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without(15%vs 5%,P<0.05).In regression analysis with age and gender adjustment,colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO.These models had a sensitivity of≥0.67,a specificity of≥0.64,and an accuracy of≥0.66.CONCLUSION The current study made key associations among colorectal polyps,SIBO,and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.
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BACKGROUND Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation.Oral probiotics are one of the postoperative treatments for rapid rehabilitation.However,there is a lack of prospective studies on this topic after appendectomy.AIM To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy.METHODS This was a prospective,randomized trial.A total of 60 emergency patients were randomly divided into a control group(n=30)and a probiotic group(n=30).Patients in the control group started to drink some water the first day after surgery,and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery.The indices of inflammation and postoperative conditions were recorded,and the data were analyzed with RStudio 4.3.2 software.RESULTS A total of 60 participants were included.Compared with those in the control group,the C-reactive protein(CRP),interleukin 6 and procalcitonin(PCT)levels were significantly lower in the probiotic group at 2 d after surgery(P=2.224e-05,P=0.037,and P=0.002,respectively,all P<0.05).This trend persisted at day 5 post-surgery,with CRP and PCT levels remaining significantly lower in the probiotic group(P=0.001 and P=0.043,both P<0.05).Furthermore,probiotics0.028,both P<0.05).CONCLUSION Postoperative oral administration of probiotics may modulate the gut microbiota,benefit the recovery of the early inflammatory response,and subsequently enhance recovery after appendectomy.
