Dietary supplementation of zinc oxide modulates intestinal functionality during the post-weaning period in clinically healthy piglets

Background To improve our understanding of host and intestinal microbiome interaction,this research investigated the effects of a high-level zinc oxide in the diet as model intervention on the intestinal microbiome and small intestinal functionality in clinically healthy post-weaning piglets.In study 1,piglets received either a high concentration of zinc(Zn)as zinc oxide(Zn O,Zn,2,690 mg/kg)or a low Zn concentration(100 mg/kg)in the diet during the post weaning period(d 14–23).The effects on the piglet's small intestinal microbiome and functionality of intestinal tissue were investigated.In study 2,the impact of timing of the dietary zinc intervention was investigated,i.e.,between d 0–14 and/or d 14–23 post weaning,and the consecutive effects on the piglet's intestinal functionality,here referring to microbiota composition and diversity and gene expression profiles.Results Differences in the small intestinal functionality were observed during the post weaning period between piglets receiving a diet with a low or high concentration Zn O content.A shift in the microbiota composition in the small intestine was observed that could be characterized as a non-pathological change,where mainly the commensals inter-changed.In the immediate post weaning period,i.e.,d 0–14,the highest number of differentially expressed genes(DEGs)in intestinal tissue were observed between animals receiving a diet with a low or high concentration Zn O content,i.e.,23 DEGs in jejunal tissue and 11 DEGs in ileal tissue.These genes are involved in biological processes related to immunity and inflammatory responses.For example,genes CD59 and REG3G were downregulated in the animals receiving a diet with a high concentration Zn O content compared to low Zn O content in both jejunum and ileum tissue.In the second study,a similar result was obtained regarding the expression of genes in intestinal tissue related to immune pathways when comparing piglets receiving a diet with a high concentration Zn O content compared to low Zn O content.Conclusions Supplementing a diet with a pharmaceutical level of Zn as Zn O for clinically healthy post weaning piglets influences various aspects intestinal functionality,in particular in the first two weeks post-weaning.The model intervention increased both the alpha diversity of the intestinal microbiome and the expression of a limited number of genes linked to the local immune system in intestinal tissue.The effects do not seem related to a direct antimicrobial effect of Zn O.

Effects of Enteromorpha prolifera polysaccharides on growth performance,intestinal barrier function and cecal microbiota in yellow-feathered broilers under heat stress

Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.

The synbiotic mixture of lactulose and Bacillus coagulans protects intestinal barrier dysfunction and apoptosis in weaned piglets challenged with lipopolysaccharide

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.

Synergistic effects of alginate oligosaccharide and cyanidin-3-O-glucoside on the amelioration of intestinal barrier function in mice

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.

Gut microbiota absence and transplantation affect growth and intestinal functions:An investigation in a germ-free pig model

This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free(GF)pig model.Twelve hysterectomy-derived GF Bama piglets were reared in 6 sterile isolators.Among them,6 were considered as the GF group,and the other 6 were orally inoculated with healthy sow fecal suspension as fecal microbiota transplanted(FMT)group.Another 6 piglets from natural birth were regarded as the conventional(CV)group.The GF and FMT groups were hand-fed with Co60-y-irradiated sterile milk powder,while the CV group was reared by lactating Bama sows.All groups were fed for 21 days.Then,all piglets and then were switched to sterile feed for another 21 days.Results showed that the growth performance,nutrient digestibility,and concentrations of short-chain fatty acids in the GF group decreased(P<0.05).Meanwhile,the serum urea nitrogen concentration and digesta pH values in the GF group increased compared with those in the FMT and CV groups(P<0.05).Compared with the CV group,the GF group demonstrated upregulation in the mRNA expression levels of intestinal barrier function-related genes in the small intestine(P<0.05).In addition,the mRNA abundances of intestinal development and absorption-related genes in the small intestine and colon were higher in the GF group than in the CV and FMT groups(P<0.05).The FMT group exhibited greater growth performance,lipase activity,and nutrient digestibility(P<0.05),higher mRNA expression levels of intestinal development and barrier-related genes in the small intestine(P<0.05),and lower mRNA abundances of pro-inflammatory factor in the colon and jejunum(P<0.05)than the CV group.In conclusion,the absence of gut microbes impaired the growth and nutrient digestibility,and healthy sow gut microbiota transplantation increased the growth and nutrient digestibility and improved the intestinal development and barrier function of newborn piglets,indicating the importance of intestinal microbes for intestinal development and functions.

Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota

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.

Dietary garcinol supplementation improves diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets

Background:The effects of dietary garcinol on diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets were investigated.Method:One hundred forty four weaned piglets(Duroc×Yorkshire×Landrace)from 16 pens(9 piglets per pen)were randomly divided into four treatment groups:controls(CON)or those supplemented with 200 mg/kg(LOW),400 mg/kg(MID),or 600 mg/kg(HIGH)diet garcinol.After 14-day trial,three piglets per pen were chosen to collect plasma,intestinal tissue and colonic digesta samples.Results:We demonstrated for the first time that garcinol promoted growth performance,as increased average daily feed intake(ADFI)and decreased feed/gain ratio(F/G);and reduced diarrhea incidence(P<0.05);and strengthened antioxidant capacity,as an increased antioxidative index(P<0.05).Additionally,garcinol ameliorated intestinal barrier dysfunction,as an increased villus height to crypt depth ratio,increased zonula occludens protein 1(ZO-1),occludin and claudin-1 expression in the jejunum and ileum(P<0.05),and decreased intestinal permeability(P<0.05);and reduced inflammation,as decreased cytokine interleukin(IL)-6,IL-10,IL-1βand tumor necrosis factor-α(TNF-α)levels in the mucosa of the jejunum and ileum,and NF-κB p65 translocation(P<0.05).Moreover,garcinol inhibited the growth of most harmful bacteria in the gut,especially Escherichia coli,and increased the growth of the beneficial bacteria Lactobacillus.Conclusion:This work provides a fundamental basis for the future development of garcinol-functional food use for improving diarrhea and intestinal barrier function in weaned piglets and for understanding the biological effects of garcinol and its potential as a functional feed additive.

Effect of EPEC endotoxin and bifidobacteria on intestinal barrier function through modulation of toll-like receptor 2 and toll-like receptor 4 expression in intestinal epithelial cell-18

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.

Tauroursodeoxycholic acid(TUDCA)improves intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets

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.

Influence of the Multispecies Probiotic Ecologic^(■) BARRIER on Parameters of Intestinal Barrier Function

The intestinal epithelium is a single cell layer that forms the largest and most important barrier against the external environment. A proper functioning of the intestinal barrier is essential for maintaining optimal health. A disrupted intestinal barrier function has been associated with the development of autoimmune and inflammatory diseases. Probiotics are live microorganisms that confer a health benefit to the host and have been associated with prevention of diseases such as antibiotic-associated diarrhea, irritable bowel syndrome and inflammatory bowel disease. Probiotics can improve and restore the intestinal barrier function in diverse ways and effects are thought to be species- and even strain-specific. With this research the influence of probiotic bacteria in Ecologic? BARRIER on parameters of intestinal barrier function was investigated. The results show that each bacterial strain in Ecologic?BARRIER is in vitro capable to improve the epithelial barrier in diverse ways.

Growth efficiency,intestinal biology,and nutrient utilization and requirements of black soldier fly(Hermetia illucens)larvae compared to monogastric livestock species:a review

In recent years,interest in the larvae of black soldier fly(BSF)(Hermetia illucens)as a sustainable protein resource for livestock feed has increased considerably.However,knowledge on the nutritional and physiological aspects of this insect,especially compared to other conventional farmed animals is scarce.This review presents a critical comparison of data on the growth potential and efficiency of the BSF larvae(BSFL)compared to conventional monogastric livestock species.Advantages of BSFL over other monogastric livestock species includes their high growth rate and their ability to convert low-grade organic waste into high-quality protein and fat-rich biomass suitable for use in animal feed.Calculations using literature data suggest that BSFL are more efficient than broilers,pigs and fish in terms of conversion of substrate protein into body mass,but less efficient than broilers and fish in utilization of substrate gross energy to gain body mass.BSFL growth efficiency varies greatly depending on the nutrient quality of their dietary substrates.This might be associated with the function of their gastrointestinal tract,including the activity of digestive enzymes,the substrate particle characteristics,and their intestinal microbial community.The conceived advantage of BSFL having an environmental footprint better than conventional livestock is only true if BSFL is produced on low-grade organic waste and its protein would directly be used for human consumption.Therefore,their potential role as a new species to better close nutrient cycles in agro-ecological systems needs to be reconsidered,and we conclude that BSFL is a complementary livestock species efficiently utilizing organic waste that cannot be utilized by other livestock.In addition,we provide comparative insight into morpho-functional aspects of the gut,characterization of digestive enzymes,gut microbiota and fiber digestion.Finally,current knowledge on the nutritional utilization and requirements of BSFL in terms of macro-and micronutrients is reviewed and found to be rather limited.In addition,the research methods to determine nutritional requirements of conventional livestock are not applicable for BSFL.Thus,there is a great need for research on the nutrient requirements of BSFL.

Supplementation of oligosaccharide-based polymer enhanced growth and disease resistance of weaned pigs by modulating intestinal integrity and systemic immunity

Background:There is a great demand for antibiotic alternatives to maintain animal health and productivity.The objective of this experiment was to determine the efficacy of dietary supplementation of a blood group A6 type 1antigen oligosaccharides-based polymer(Coligo)on growth performance,diarrhea severity,intestinal health,and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC),when compared with antibiotics.Results:Pigs in antibiotic carbadox or Coligo treatment groups had greater(P<0.05)body weight on d 5 or d 11post-inoculation(PI)than pigs in the control group,respectively.Supplementation of antibiotics or Coligo enhanced(P<0.05)feed efficiency from d 0 to 5 PI and reduced(P<0.05)frequency of diarrhea throughout the experiment,compared with pigs in the control group.Supplementation of antibiotics reduced(P<0.05)fecalβ-hemolytic coliforms on d 2,5,and 8 PI.Pigs in antibiotics or Coligo groups had reduced(P<0.05)neutrophil counts and serum haptoglobin concentration compared to pigs in the control group on d 2 and 5 PI.Pigs in Coligo had reduced(P<0.05)total coliforms in mesenteric lymph nodes on d 5 and 11 PI,whereas pigs in antibiotics or Coligo groups had reduced(P<0.05)total coliforms in spleen on d 11 PI compared with pigs in the control group.On d 5 PI,pigs in the Coligo group had greater(P<0.05)gene expression of ZO1 in jejunal mucosa,but less(P<0.05)m RNA expression of IL1B,IL6,and TNF in ileal mucosa,in comparison with pigs in the control group.Supplementation of antibiotics enhanced(P<0.05)the gene expression of OCLN in jejunal mucosa but decreased(P<0.05)IL1B and IL6 gene expression in ileal mucosa,compared with the control.On d 11 PI,supplementation of antibiotics or Coligo up-regulated(P<0.05)gene expression of CLDN1 in jejunal mucosa,but Coligo reduced(P<0.05)IL6 gene expression in ileal mucosa compared to pigs in the control group.Conclusions:Supplementation of Coligo improved growth performance,alleviated diarrhea severity,and enhanced gut health in weaned pigs infected with ETEC F18 in a manner similar to in-feed antibiotics.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth

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.

Electroacupuncture alleviates water avoidance stress-induced irritable bowel syndrome in mice by improving intestinal barrier functions and suppressing the expression of inflammatory cytokines

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.

New insights into the unfolded protein response(UPR)-anterior gradient 2(AGR2)pathway in the regulation of intestinal barrier function in weaned piglets

Sustained dysfunction of the intestinal barrier caused by early weaning is a major factor that induces postweaning diarrhea in weaned piglets.In both healthy and diseased states,the intestinal barrier is regulated by goblet cells.Alterations in the characteristics of goblet cells are linked to intestinal barrier dysfunction and inflammatory conditions during pathogenic infections.In this review,we summarize the current understanding of the mechanisms of the unfolded protein response(UPR)and anterior gradient2(AGR2)in maintaining intestinal barrier function and how modifications to these systems affect mucus barrier characteristics and goblet cell dysregulation.We highlight a novel mechanism underlying the UPR-AGR2 pathway,which affects goblet cell differentiation and maturation and the synthesis and secretion of mucin by regulating epidermal growth factor receptor and mucin 2.This study provides a theoretical basis and new insights into the regulation of intestinal health in weaned piglets.

1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex

Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treatment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate sodium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mechanistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.

Effect of ultrasound-guided lumbar square muscle block on stress response in patients undergoing radical gastric cancer surgery

BACKGROUND Radical surgery is a common treatment for patients with gastric cancer;however,it can lead to postoperative complications and intestinal barrier dysfunction.Ultrasound-guided quadratus lumborum block is often used for postoperative analgesia,but its effects on stress response and intestinal barrier function are not well understood.AIM To investigate the effects of an ultrasound-guided quadratus lumborum block on stress response and intestinal barrier function in patients undergoing radical surgery for gastric cancer.METHODS A total of 100 patients undergoing radical surgery for gastric cancer were randomly categorized into observation and control groups.Plasma adrenaline and cortisol levels,intestinal mucosal barrier indexes,and complication rates were compared between the two groups before,during,and 1 day after surgery.RESULTS The observation group had significantly lower plasma adrenaline and cortisol levels during surgery and at 1 day postoperatively than that of the control group(P<0.05).Additionally,intestinal barrier indexes(endotoxin and D-dimer)at 1 day postoperatively were significantly lower in the observation group than in the control group(P<0.05).CONCLUSION Ultrasound-guided quadratus lumborum block could reduce stress response,protect intestinal barrier function,and decrease the incidence of complications in patients undergoing radical surgery for gastric cancer.This technique has the potential for clinical applications.

Analgesic effect of ultrasound-guided bilateral transversus abdominis plane block in laparoscopic gastric cancer

BACKGROUND Postoperative complications are important factors affecting the survival time and quality of life of patients undergoing radical gastrectomy.AIM To investigate and compare the anesthetic effects of intravenous general anesthesia combined with epidural anesthesia or ultrasound-guided bilateral transversus abdominal plane block(TAPB)in gastric cancer patients undergoing laparoscopic radical gastrectomy.METHODS The clinical data of 85 patients who underwent laparoscopic radical gastrectomy in our hospital from December 2020 to January 2023 were retrospectively collected and divided into a TAPB group(n=45)and epidural anesthesia group(n=40)according to the different anesthesia and analgesia programs used.The TAPB group received general anesthesia combined with TAPB,and the epidural anesthesia group received general anesthesia combined with epidural anesthesia.The pain status,cognitive status,intestinal barrier indicators,recovery quality,and incidence of complications were compared between the two groups.RESULTS Compared with the epidural anesthesia group,the TAPB group’s visual analog scale scores were significantly lower 6 h,12 h,24 h and 48 h after surgery(P<0.05).The incidence of postoperative cognitive dysfunction(POCD)in the TAPB group was significantly lower than that in the epidural anesthesia group,and the Mini-mental State Examination score 24 h after surgery was significantly higher in the TAPB group than the epidural anesthesia group(P<0.05).The levels of diamine oxidase and plasma D-lactate were significantly lower in the TAPB group than the epidural anesthesia group 24 h after surgery(P<0.05).The agitation score and the incidence of agitation during recovery were significantly lower in the TAPB group than epidural anesthesia group(P<0.05).The total incidence of postoperative complications in the TAPB group was 4.44%,significantly lower than the 20.00%in the epidural anesthesia group(P<0.05).CONCLUSION Compared with epidural anesthesia combined with general anesthesia,TAPB combined with general anesthesia had a good analgesic effect in laparoscopic radical gastrectomy and can further reduce the incidence of POCD and postoperative complications,improve the levels of intestinal barrier indicators,and improve postoperative recovery quality.

Porcine intestinal antimicrobial peptide as an in-feed antibiotic alternative improves intestinal digestion and immunity by shaping the gut microbiota in weaned piglets

Antibiotic resistance of pathogens,which is caused by the abuse of in-feed antibiotics,threatens the sustainable development of livestock production.The present study aimed to investigate the efficiency of porcine intestinal antimicrobial peptide(PIAP)as an alternative to in-feed antibiotics in terms of growth performance,intestinal morphology,digestive enzymes and immunity,and microbiota community of the post-weaning piglets.A total of 204 piglets(Duroc×Landrace×Yorkshire,weaned at 28 d age)with a similar body weight of 7.97±1.04 kg were randomly allocated to 4 groups(51 piglets per group):(1)control group:basal diet;(2)AB group:antibiotic,basal diet+chlortetracycline(1000 mg/kg from d 1 to24;500 mg/kg from d 25 to 37);(3)P1 group:basal diet+a relatively low dose of PIAP(400 mg/kg from d 1 to 24;300 mg/kg from d 25 to 37);(4)P2 group,basal diet+a relatively high dose of PIAP(600 mg/kg from d 1 to 24;500 mg/kg from d 25 to 37).The results showed that serum indicators of hepatocyte damage and relative organ weight were not affected by these treatments(P>0.05).Compared with the AB treatment,the P1 treatment remarkably decreased jejunal crypt depth and increased jejunal and ileal villus height:crypt depth ratio(P<0.05).The values of jejunal maltase,lactase,sucrase,intestinal alkaline phosphatase,and secretory immunoglobulin A(SIg A)in the P1 group were sharply increased compared with those in the control and P2 groups(P<0.05).Compared with the control group,the P1 group decreased serum concentrations of D-lactate,diamine oxidase,and endotoxin(P<0.05),and increased the abundance of Lactobacillus reuteri(P<0.05)in the colonic feces.Furthermore,there was a positive correlation between the abundance of L.reuteri and the concentrations of maltase,lactase,sucrase,and SIg A(P<0.05).Collectively,dietary supplementation with a relatively low dose of PIAP(400 mg/kg from d 1 to 24;300 mg/kg from d 25 to 37)demonstrates beneficial effects on intestinal morphology,digestive enzymes,immunity,and permeability by shaping the gut microbiota composition in weaned piglets.This study will provide a valuable reference for using PIAP as an in-feed antibiotic alternative in swine production.

Low crude protein diets supplemented with casein hydrolysate enhance the intestinal barrier function and decrease the pro-inflammatory cytokine expression in the small intestine of pigs

To reduce nitrogen excretion and lower feeding costs,low crude protein(CP)diets are sometimes pro-posed,however,a great reduction of dietary CP concentration(>4%reduction vs.recommended con-centration),even supplemented with essential and nonessential amino acids(AA)can detrimentally affect small intestinal barrier function and immunity,possibly due to the excessive lack of peptides.Here we hypothesize that with an extremely low CP concentration diet,protein-derived peptides,rather than AA supplementation,can improve intestinal barrier development and health.To test this hypothesis,21 growing pigs(19.90±1.00 kg body weight)were randomly assigned to 3 treatments with control diet(16%CP),or low CP diets(13%CP)supplemented with AA(LCPA)or casein hydrolysate(LCPC)for 28 days.In comparison with the control diet,the LCPA diet decreased the protein expression level of jejunal barrier factor zonula occludens-1(ZO-1)and stem cell proliferation factor leucine-rich repeat-containing G-protein-coupled receptor-5,whereas the LCPC diet enhanced intestinal barrier function by increasing the protein expression level of jejunal occludin and ZO-1 and ileal mucin-2.The LCPA diet reduced Lactobacillus counts,whereas the LCPC diet increased Lactobacillus counts and reduced Escherichia coli counts in the ileum.The LCPA diet also increased protein expression levels of pro-inflammatory cytokine interleukin-6(IL-6)and IL-22,whereas the LCPC diet decreased protein expression levels of pro-inflammatory IL-1β,IL-17A and tumor necrosis factor-αin the ileum.Collectively,the casein hydroly-sate supplementation of low CP diets showed beneficial effects on the small intestinal barrier,bacterial community,and immunity in pigs,pointing to the important role of protein-derived peptides in small intestinal health in cases of low crude protein diets.