Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are ra...BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.展开更多
BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recover...BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recovery of gastrointestinal function in children.AIM To compare and analyze the effects of different postoperative feeding methods on gastrointestinal function reconstruction in newborns with CIA.METHODS Twenty-six children diagnosed with neonatal CIA,treated with minimally invasive surgery at Shijiazhuang Maternal and Child Health Hospital between January 2021 and May 2024,were selected for this single-center prospective randomized controlled study.They were divided into two groups using envelope randomization:Enteral nutrition(EN)group(n=13)and parenteral nutrition(PN)group(n=13).Baseline and clinical characteristics were collected,and recovery time of bowel sounds and time to first defecation were used as evaluation indices for gastrointestinal functional reconstruction.Differences between the groups were analyzed using t-test,χ2 test,and Fisher’s exact test.Spearman’s correlation tests and linear regression models were employed to analyze factors influencing time to first defecation.RESULTS The time to bowel sound recovery(51.54 vs 65.85,P=0.013)and first defecation(58.15 vs 76.62,P<0.001)was shorter in the EN group compared to the PN group.Clinical improvements in the EN group,including discharge weight(P=0.044),hospital stay(P=0.027),white blood cell count(P=0.023),albumin content(P=0.013),and direct bilirubin content(P=0.018),were also better than those in the PN group.No substantial differences in postoperative complications were found between the groups.Correlation analysis indicated that abdominal infection and operation time may relate to time to first defecation.Linear regression analysis demonstrated a considerable association between EN feeding and shorter time to first defecation.Abdominal infection and an operation time>2 hours may be risk factors for prolonged time to first defecation.CONCLUSION EN substantially promotes the recovery of gastrointestinal function after CIA in neonates and can improve clinical outcomes in children.Future research should explore optimal EN practices to enhance clinical application and child health.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
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
Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechan...Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechanisms by which AOS regulates porcine growth remain to be elucidated. Therefore, we investigated the AOS-mediated changes in the growth performance of weaned pigs by determining the intestinal morphology, barrier function,as well as epithelium apoptosis.Methods: Twenty-four weaned pigs were distributed into two groups(n = 12) and received either a basal diet(control group) or the same diet supplemented with 100 mg/kg AOS. On d 15, D-xylose(0.1 g/kg body weight)was orally administrated to eight randomly selected pigs per treatment, and their serum and intestinal mucosa samples were collected 1 h later.Results: Our results showed that inclusion of AOS in the diet for 2 wk increased(P < 0.05) the average daily body weight gain in weaned pigs. Notably, AOS supplementation ameliorated the intestinal morphology and barrier function, as suggested by the enhanced(P < 0.05) intestinal villus height, secretory immunoglobulin A content and goblet cell counts. Compared to the control group, AOS ingestion both decreased(P < 0.05) the total apoptotic percentage and increased(P < 0.05) the proportion of S phase in the intestinal epithelial cells. Furthermore, AOS not only up-regulated(P < 0.05) the B-cell lymphoma-2(BCL2) transcriptional level but also down-regulated(P < 0.05) the B-cell lymphoma-2-associated X protein(BAX), cysteinyl aspartate-specific proteinase-3(caspase-3) and caspase-9 transcriptional levels in the small intestine.Conclusions: In summary, this study provides evidence that supplemental AOS beneficially affects the growth performance of weaned pigs, which may result from the improved intestinal morphology and barrier function,as well as the inhibited enterocyte death, through reducing apoptosis via mitochondria-dependent apoptosis.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.
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
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 Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in se...BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.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 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
The goal of this study was to evaluate the effects of a mixture of yeast culture,cell wall hydrolysates,and yeast extracts(collectively"yeast products,"YP)on the performance,intestinal physiology,and health ...The goal of this study was to evaluate the effects of a mixture of yeast culture,cell wall hydrolysates,and yeast extracts(collectively"yeast products,"YP)on the performance,intestinal physiology,and health of weaned piglets.A total of 90 piglets weaned at 21 d of age were blocked by body weight,sex,and litter and randomly assigned to one of three treatments for a 14-d feeding experiment,including(1)a basal diet(control),(2)1.2 g/kg of YP,and(3)20 mg/kg of colistin sulfate(CSE).No statistically significant differences were observed in average daily feed intake,average daily weight gain,or gain-to-feed ratio among CSE,YP,and control piglets.Increased prevalence of diarrhea was observed among piglets fed the YP diet,whereas diarrhea was less prevalent among those fed CSE.Duodenal and jejunal villus height and duodenal crypt depth were greater in the control group than they were in the YP or CSE groups.Intraepithelial lymphocytes(IEL)in the duodenal and jejunal villi were enhanced by YP,whereas IEL in the ileal villi were reduced in weaned piglets fed YP.Secretion of jejunal and ileal interleukin-10(IL-10)was higher and intestinal and serum antioxidant indexes were affected by YP and CSE.In YP-and CSE-supplemented animals,serum D-lactate concentration and diamine oxidase(DAO)activity were both increased,and intestinal mR NA expressions of occludin and ZO-1 were reduced as compared to the control animals.In conclusion,YP supplementation in the diets of weaned piglets appears to increase the incidence of diarrhea and has adverse effects on intestinal morphology and barrier function.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
The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different dis...The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can, strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or animal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans. Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with probiotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating a clear potential of probiotics in this field. In a case series of 14 patients using Ecologica825, a probiotic food supplement with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly. Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin might be valuable markers to measure epithelial barrier function in future experiments.展开更多
Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mech...Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mechanism of BZBS in the treatment of functional constipation(FC)has been little studied and remains unclear.In this study,a behavioral investigation,colon tissue morphology,enzyme-linked immunosorbent assay(Elisa)and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model.Methods:A FC rat model was constructed and BZBS was given as treatment.Observations and recordings were made of the fecal moisture content,the defecation time of the first black stool,and the rate of intestinal propulsion.Elisa was used to detect the expression levels of substance P(SP),vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT)in the colon.To ascertain the composition of the microbial community,a high throughput 16S ribosomal RNA(16S r RNA)gene sequencing technique was employed.Results:Oral administration of BZBS significantly ameliorated several key excretion parameters,including the time to first black stool defecation,stool water content,and the propulsion rate in the small intestine in FC rats.It increased the expression of SP,VIP and 5-HT in the colon.16S r RNA gene sequencing results showed that BZBS changed the microbial community structure,decreased the Bacteroidetes/Firmicutes ratio,increased the relative abundance of Blautia and Fusicatenibacter,and decreased the relative abundance of Ruminococcus and Roseburia.Conclusions:BZBS effectively alleviates FC and improves dysbacteriosis.展开更多
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
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
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
文摘BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.
文摘BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recovery of gastrointestinal function in children.AIM To compare and analyze the effects of different postoperative feeding methods on gastrointestinal function reconstruction in newborns with CIA.METHODS Twenty-six children diagnosed with neonatal CIA,treated with minimally invasive surgery at Shijiazhuang Maternal and Child Health Hospital between January 2021 and May 2024,were selected for this single-center prospective randomized controlled study.They were divided into two groups using envelope randomization:Enteral nutrition(EN)group(n=13)and parenteral nutrition(PN)group(n=13).Baseline and clinical characteristics were collected,and recovery time of bowel sounds and time to first defecation were used as evaluation indices for gastrointestinal functional reconstruction.Differences between the groups were analyzed using t-test,χ2 test,and Fisher’s exact test.Spearman’s correlation tests and linear regression models were employed to analyze factors influencing time to first defecation.RESULTS The time to bowel sound recovery(51.54 vs 65.85,P=0.013)and first defecation(58.15 vs 76.62,P<0.001)was shorter in the EN group compared to the PN group.Clinical improvements in the EN group,including discharge weight(P=0.044),hospital stay(P=0.027),white blood cell count(P=0.023),albumin content(P=0.013),and direct bilirubin content(P=0.018),were also better than those in the PN group.No substantial differences in postoperative complications were found between the groups.Correlation analysis indicated that abdominal infection and operation time may relate to time to first defecation.Linear regression analysis demonstrated a considerable association between EN feeding and shorter time to first defecation.Abdominal infection and an operation time>2 hours may be risk factors for prolonged time to first defecation.CONCLUSION EN substantially promotes the recovery of gastrointestinal function after CIA in neonates and can improve clinical outcomes in children.Future research should explore optimal EN practices to enhance clinical application and child health.
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supported by the Special Fund for Agro-scientific Research in the Public Interest(201403047)
文摘Background: Alginate oligosaccharide(AOS), produced from alginate by alginate lyase-mediated depolymerisation, is a potential substitute for antibiotics and possesses growth-enhancing effects. Nevertheless, the mechanisms by which AOS regulates porcine growth remain to be elucidated. Therefore, we investigated the AOS-mediated changes in the growth performance of weaned pigs by determining the intestinal morphology, barrier function,as well as epithelium apoptosis.Methods: Twenty-four weaned pigs were distributed into two groups(n = 12) and received either a basal diet(control group) or the same diet supplemented with 100 mg/kg AOS. On d 15, D-xylose(0.1 g/kg body weight)was orally administrated to eight randomly selected pigs per treatment, and their serum and intestinal mucosa samples were collected 1 h later.Results: Our results showed that inclusion of AOS in the diet for 2 wk increased(P < 0.05) the average daily body weight gain in weaned pigs. Notably, AOS supplementation ameliorated the intestinal morphology and barrier function, as suggested by the enhanced(P < 0.05) intestinal villus height, secretory immunoglobulin A content and goblet cell counts. Compared to the control group, AOS ingestion both decreased(P < 0.05) the total apoptotic percentage and increased(P < 0.05) the proportion of S phase in the intestinal epithelial cells. Furthermore, AOS not only up-regulated(P < 0.05) the B-cell lymphoma-2(BCL2) transcriptional level but also down-regulated(P < 0.05) the B-cell lymphoma-2-associated X protein(BAX), cysteinyl aspartate-specific proteinase-3(caspase-3) and caspase-9 transcriptional levels in the small intestine.Conclusions: In summary, this study provides evidence that supplemental AOS beneficially affects the growth performance of weaned pigs, which may result from the improved intestinal morphology and barrier function,as well as the inhibited enterocyte death, through reducing apoptosis via mitochondria-dependent apoptosis.
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 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 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 National Natural Science Foundation of China,No.81701881Nanjing Medical Science and Technology Development Foundation,No.YKK17102.
文摘BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.
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 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 Natural Science Foundation of China(Nos.31330075,31402089,31301988,31572420,31272450,and 31272451)the National Key Technology R&D Program of China(No.2016YFD0500504)+2 种基金the Changsha Lvye Biotechnology Limited Company Academician Expert Workstationthe Guangdong Hinapharm Group Academician Workstation for Biological Feed and Feed Additivesthe Animal Intestinal Health Hunan New Wellful Co.,Ltd.,Academician Workstation,Changsha,China
文摘The goal of this study was to evaluate the effects of a mixture of yeast culture,cell wall hydrolysates,and yeast extracts(collectively"yeast products,"YP)on the performance,intestinal physiology,and health of weaned piglets.A total of 90 piglets weaned at 21 d of age were blocked by body weight,sex,and litter and randomly assigned to one of three treatments for a 14-d feeding experiment,including(1)a basal diet(control),(2)1.2 g/kg of YP,and(3)20 mg/kg of colistin sulfate(CSE).No statistically significant differences were observed in average daily feed intake,average daily weight gain,or gain-to-feed ratio among CSE,YP,and control piglets.Increased prevalence of diarrhea was observed among piglets fed the YP diet,whereas diarrhea was less prevalent among those fed CSE.Duodenal and jejunal villus height and duodenal crypt depth were greater in the control group than they were in the YP or CSE groups.Intraepithelial lymphocytes(IEL)in the duodenal and jejunal villi were enhanced by YP,whereas IEL in the ileal villi were reduced in weaned piglets fed YP.Secretion of jejunal and ileal interleukin-10(IL-10)was higher and intestinal and serum antioxidant indexes were affected by YP and CSE.In YP-and CSE-supplemented animals,serum D-lactate concentration and diamine oxidase(DAO)activity were both increased,and intestinal mR NA expressions of occludin and ZO-1 were reduced as compared to the control animals.In conclusion,YP supplementation in the diets of weaned piglets appears to increase the incidence of diarrhea and has adverse effects on intestinal morphology and barrier function.
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.
文摘The intestinal barrier is important in preventing translocation of bacteria, toxins and antigens from the lumen of the gut into the body. Enhanced permeability, or gut leakiness, has been associated with different diseases. Probiotics can, strain-specifically, improve the epithelial barrier function. However, so far most researches have used cell lines or animal models due to the difficulty of measuring the effects of products on the epithelial barrier function in vivo in humans. Here a systematic literature search was performed to find articles addressing the effects of probiotics on the barrier function in human trials. The Pubmed database was searched (January 2013) to identify human in vivo studies with probiotic products in which parameters for epithelial barrier function were measured. In total 29 studies were identified, but patients, bacterial characteristics and methods to measure intestinal barrier function caused large heterogeneity among these studies. About half of the studies showed positive results of probiotics on the epithelial barrier function, indicating a clear potential of probiotics in this field. In a case series of 14 patients using Ecologica825, a probiotic food supplement with known effect on epithelial barrier function, different markers of intestinal integrity improved significantly. Further studies in this field should consider strain(s), dose and duration of the probiotic supplementation as well as the markers used to measure epithelial barrier function. Besides the lactulose/mannitol test, zonulin and α1-antitrypsin might be valuable markers to measure epithelial barrier function in future experiments.
基金Natural Science Foundation of Zhejiang Province,Grant/Award Number:Y19H280022。
文摘Background:In China,Rhizoma atractylodis macrocephalae-Paeonia lactiflora Pall(Biazhu-Baishao,BZBS)is a classic herb pair used to treat intestinal stress syndrome,ulcerative colitis and other diseases.However,the mechanism of BZBS in the treatment of functional constipation(FC)has been little studied and remains unclear.In this study,a behavioral investigation,colon tissue morphology,enzyme-linked immunosorbent assay(Elisa)and intestinal microflora analysis have been used to illuminate the potential mechanism of the effects of BZBS on FC in a rat model.Methods:A FC rat model was constructed and BZBS was given as treatment.Observations and recordings were made of the fecal moisture content,the defecation time of the first black stool,and the rate of intestinal propulsion.Elisa was used to detect the expression levels of substance P(SP),vasoactive intestinal peptide(VIP),5-hydroxytryptamine(5-HT)in the colon.To ascertain the composition of the microbial community,a high throughput 16S ribosomal RNA(16S r RNA)gene sequencing technique was employed.Results:Oral administration of BZBS significantly ameliorated several key excretion parameters,including the time to first black stool defecation,stool water content,and the propulsion rate in the small intestine in FC rats.It increased the expression of SP,VIP and 5-HT in the colon.16S r RNA gene sequencing results showed that BZBS changed the microbial community structure,decreased the Bacteroidetes/Firmicutes ratio,increased the relative abundance of Blautia and Fusicatenibacter,and decreased the relative abundance of Ruminococcus and Roseburia.Conclusions:BZBS effectively alleviates FC and improves dysbacteriosis.
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.
