Background： Necrotic enteritis caused by Clostfidium perffingens infection leads to serious economic losses in the global poultry production. In the present study, we investigated the protective effects of essential ...Background： Necrotic enteritis caused by Clostfidium perffingens infection leads to serious economic losses in the global poultry production. In the present study, we investigated the protective effects of essential oils （EO, which contained 25 % thymol and 25 % carvacrol as active components） supplementation on growth performance, gut lesions, intestinal morphology, and immune responses of the broiler chickens infected with C. perfringens. A total of 448 1-day-old male broiler chicks were allocated into eight treatment groups following a 4 x 2 factorial arrangement with four dietary EO dosages （0, 60, 120, or 240 mg/kg） and two infection status （with or without C. perfringens challenge from d 14 to 20）. Results： The challenge did not impair the growth performance of birds, but induced gut lesions and increased crypt depth in the ileum （P ≤ 0.05）. It also down-regulated the claudin-1 and occludin mRNA expression （P ≤0.05）, up-regulated the mRNA expression of interleukin-113 （P≤ 0.05）, tended to increase the toll-like receptor （TLR） 2 mRNA expression （P 〈 0.10） in the ileum, and enhanced the mucosal secretory IgA production （P 〈 0.05）. In the challenged birds, dietary EO supplementation linearly alleviated the gut lesions and improved the ratio of villus height to crypt depth （P ≤0.05）, and the supplementation of 120 and 240 mg/kg EO increased the serum antibody titers against Newcastle disease virus （P≤ 0.05）. Regardless of challenge, the EO supplementation showed a tendency to linearly elevate the feed conversion efficiency between 14 and 28 d of age as well as the occludin mRNA expression （P〈 0.10）, and linearly inhibited the mRNA expression of TLR2 and tumor necrotic factor-o in the ileum （P≤ 0.05）. Conclusions： The dietary supplementation of EO could alleviate the intestinal injury by improving intestinal integrity and modulating immune responses in the C. perffingens-challenged broiler chickens.展开更多
Background Cetobacterium somerae,a symbiotic microorganism resident in various fish intestines,is recognized for its beneficial effects on fish gut health.However,the mechanisms underlying the effects of C.somerae on ...Background Cetobacterium somerae,a symbiotic microorganism resident in various fish intestines,is recognized for its beneficial effects on fish gut health.However,the mechanisms underlying the effects of C.somerae on gut health remain unclear.In this experiment,we investigated the influence of C.somerae(CGMCC No.28843)on the growth performance,intestinal digestive and absorptive capacity,and intestinal structural integrity of juvenile grass carp(Ctenopharyngodon idella)and explored its potential mechanisms.Methods A cohort of 2,160 juvenile grass carp with an initial mean body weight of 11.30±0.01 g were randomly allocated into 6 treatment groups,each comprising 6 replicates(60 fish per replicate).The experimental diets were supplemented with C.somerae at graded levels of 0.00(control),0.68×10^(9),1.35×10^(9),2.04×10^(9),2.70×10^(9),and 3.40×10^(9)cells/kg feed.Following a 10-week experimental period,biological samples were collected for subsequent analyses.Results Dietary supplementation with C.somerae at 1.35×10^(9)cells/kg significantly enhanced growth performance,intestinal development,and nutrient retention rate in juvenile grass carp(P<0.05).The treatment resulted in increased intestinal acetic acid concentration and enhanced activities of digestive enzymes and brush border enzymes(P<0.05).Furthermore,it reduced intestinal permeability(P<0.05),preserved tight junctions(TJ)ultrastructural integrity,and increased the expression of TJ and adherens junctions(AJ)biomarkers at both protein and transcriptional levels(P<0.05).Mechanistically,these effects may be correlated with enhanced antioxidant capacity and coordinated modulation of the RhoA/ROCK,Sirt1,and PI3K/AKT signaling pathways.The appropriate supplementation levels,based on weight gain rate,feed conversion ratio,the activity of serum diamine oxidase and the content of lipopolysaccharide,were 1.27×10^(9),1.27×10^(9),1.34×10^(9)and 1.34×10^(9)cells/kg,respectively.Conclusions C.somerae improved intestinal digestive and absorptive capacity of juvenile grass carp,maintained intestinal structural integrity,and thus promoted their growth and development.This work demonstrates the potential of C.somerae as a probiotic for aquatic animals and provides a theoretical basis for its utilization in aquaculture.展开更多
BACKGROUND Kushenol I(KSCI)exhibits potential anti-inflammatory and antioxidant activities.However,its therapeutic effects and mechanisms in ulcerative colitis(UC)remain unclear.AIM To investigate the therapeutic effe...BACKGROUND Kushenol I(KSCI)exhibits potential anti-inflammatory and antioxidant activities.However,its therapeutic effects and mechanisms in ulcerative colitis(UC)remain unclear.AIM To investigate the therapeutic effects and mechanisms of KSCI in alleviating UC.METHODS Therapeutic targets for KSCI in treating UC were identified using network pharmacology.Molecular docking and dynamics simulations confirmed the interactions between KSCI and these targets.In a murine UC model induced by dextran sodium sulfate(DSS),the anti-inflammatory and antioxidant effects of KSCI were evaluated following oral administration,as well as its impact on intestinal barrier function and immune response modulation.Finally,changes in gut microbiota composition were analyzed using 16S ribosomal RNA sequencing.RESULTS A total of 192 potential targets of KSCI in treating UC were identified using network pharmacology.KSCI bound stably to core targets including protein kinase B(AKT),p38 mitogen-activated protein kinase(p38 MAPK),NOD-like receptor thermal protein domain associated protein 3(NLRP3),phosphoinositide 3-kinase(PI3K),forkhead box O1(FOXO1),and Toll-like receptor 4(TLR4).The oral administration of KSCI improved colon length and body weight,and reduced disease activity in a mouse model of DSS-induced UC.KSCI suppressed pro-inflammatory cytokines(interleukin[IL-1β],IL-6,IL-17,and tumor necrosis factor alpha)and promoted the expression of the anti-inflammatory cytokine IL-10.It also inhibited key signaling molecules and modulated the expression of IL-1β,AKT,p38 MAPK,NLRP3,PI3K,AKT,FOXO1,and TLR4.KSCI exhibited potent antioxidant effects,ameliorating colonic inflammation and tissue damage.It improved intestinal barrier function,influenced gut microbiota composition,and increased splenic T-cell percentages.CONCLUSION KSCI alleviated DSS-induced UC by modulating gut microbiota,enhancing the intestinal barrier,reducing inflam-mation and oxidative stress,and regulating the immune response.展开更多
Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.Spermine can r...Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.Spermine can reduce stress.However,the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown.This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1(Rac1)/phospholipase C-g1(PLC-γ1)signaling pathway.In vivo,80 piglets were categorised into 4 control groups and 4 spermine groups(10 piglets per group).The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3,6 and 9 d.In vitro,we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor a(TNF-a)challenge through Rac1/PLC-γ1 signaling pathway.The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets.The serum D-lactate content was significantly decreased after spermine supplementation(P<0.05).The in vitro study found that 0.1 mmol/L spermine increased the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability(P<0.05).Further experiments demonstrated that spermine supplementation enhanced the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-a challenge(P<0.05).Collectively,spermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.展开更多
Background:Consumption of resistant starch(RS)has been associated with various intestinal and systemic health benefits,but knowledge of its effects on intestinal health and inflammatory response in stressed birds is l...Background:Consumption of resistant starch(RS)has been associated with various intestinal and systemic health benefits,but knowledge of its effects on intestinal health and inflammatory response in stressed birds is limited.Here,we examined how dietary RS supplementation from 12%raw potato starch(RPS)modulated inflammatory severity induced by lipopolysaccharide(LPS)in meat ducks.Results:LPS administration at 14,16,and 18 d(chronic challenge)decreased body weight(BW)and glucagon-like peptide 1 receptor(GLP-1R)level with higher intestinal permeability and inflammation,evident by higher proinflammatory cytokine levels.Dietary 12%RPS supplementation enhanced Claudin-1 and GLP-1R expression,along with lower levels of inflammatory factors in both ileum and serum.Microbiome analysis showed that RS treatment shifted microbial structure reflected by enriched the proportion of Firmicutes,Bifidobacterium,Ruminococcus,etc.Dietary RS addition also significantly increased the concentrations of propionate and butyrate during chronic LPS challenge.Furthermore,response to acute challenge,the ducks received 2 mg/kg BW LPS at 14 d had higher concentrations of serum endotoxins and inflammatory cytokines,as well as upregulated transcription of toll like receptor 4(TLR4)in ileum when compared to control birds.Analogous to GLP-1 agonist liraglutide,dietary RS addition decreased endotoxins and inflammation cytokines,whereas it upregulated the GLP-1 synthesis related genes expression.Meanwhile,dietary RS supplementation suppressed the acute LPS challenge-induced TLR4 transcription.Conclusions:These data suggest that dietary 12%RPS supplementation could attenuate the LPS-induced inflammation as well as intestinal injury of meat ducks,which might involve in the alteration in gut microbiota,SCFAs production and the signaling pathways of TLR4 and GLP-1/GLP-1R.展开更多
This experiment was conducted to investigate the effects of benzoic acid,Bacillus coagulans and oregano oil combined supplementation on growth performance,immune status and intestinal barrier integrity of piglets.In a...This experiment was conducted to investigate the effects of benzoic acid,Bacillus coagulans and oregano oil combined supplementation on growth performance,immune status and intestinal barrier integrity of piglets.In a 26-d experiment,25 piglets were randomly assigned to 5 treatments:1)a basal diet,negative control(NC),2)NC added with antibiotics,positive control(PC);3)NC added with benzoic acid at 3,000 g/t and Bacillus coagulans at 400 g/t(AB);4)NC added with benzoic acid at 3,000 g/t and o regano oil at 400 g/t(AO);5)NC added with 3,000 g/t benzoic acid and Bacillus coagulans at 400 g/t and oregano oil at 400 g/t(ABO);On d 27,all piglets were euthanized to obtain jejunal mucosa to measure immune status and intestinal barrier integrity.Results showed that pigs fed AB diet increased the final body weight and average daily body weight gain and decreased the ratio of feed to gain co mpared with NC group(P<0.05).Co mpared with NC group,AB,AO and ABO decreased serum tumor necrosis factor-a concentration and ABO decreased interleukin-1βconcentration in serum and jejunal mucosa(P<0.05).Compared with NC group,AB upregulated mRNA expressions of sodium-glucose cotransportel,claudin-1,occludin and mucin2 in jejunal mucosa and the populations of Bifidobacterium and Bacillus in cecal digesta(P<0.05).Compared with NC group,ABO increased jejunal mucosal occludin mRNA abundance and Bifidobacterium population in cecal digesta,and decreased Escherichia coli population in cecal digesta(P<0.05).Furthermore,AB and ABO increased Bacillus population in cecal digesta compared with PC group(P<0.05).These results indicated that dietary AB supplementation could improve growth performance and intestinal barrier integrity of piglets when fed antibiotic-free diets,which was possibly associated with the improvement of immune status and intestinal microflora.Dietary ABO supplementation is also beneficial to improve immune status and intestinal barrier integrity and micro flora of piglets.展开更多
BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modul...BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.展开更多
To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODSThis study was conducted to assess the variability o...To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODSThis study was conducted to assess the variability or stability of zonulin levels vs IgA and IgG antibodies against zonulin in blood samples from 18 controls at 0,6,24 and 30 h after blood draw.We also measured zonulin level as well as zonulin,occludin,vinculin,aquaporin 4 and glial fibrillary acidic protein antibodies in the sera of 30 patients with celiac disease and 30 controls using enzyme-linked immunosorbent assay methodology.RESULTSThe serum zonulin level in 6 out of 18 subjects was low or<2.8 ng/mL and was very close to the detection limit of the assay.The other 12 subjects had zonulin levels of>2.8 ng/mL and showed significant fluctuation from sample to sample.Comparatively,zonulin antibody measured in all samples was highly stable and reproducible from sample to sample.Celiac disease patients showed zonulin levels with a mean of 8.5 ng/mL compared to 3.7 ng/mL in controls(P<0.0001).Elevation of zonulin level at 2SD above the mean was demonstrated in 37%of celiac disease patients,while antibodies against zonulin,occludin and other tight junction proteins was detected in up to 86%of patients with celiac disease.CONCLUSIONDue to its fluctuation,a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity.Measurement of IgG and IgA antibodies against zonulin,occludin,and other tight junction proteins is proposed for the evaluation of the loss of intestinal barrier integrity.展开更多
Emerging evidence suggests that priming intestinal stem cells(ISCs)towards secretory progenitor cells is beneficial for maintaining gut homeostasis against inflammatory bowel disease(IBD).However,the mechanism driving...Emerging evidence suggests that priming intestinal stem cells(ISCs)towards secretory progenitor cells is beneficial for maintaining gut homeostasis against inflammatory bowel disease(IBD).However,the mechanism driving such biased lineage commitment remains elusive.Here we show that MG53,also named as TRIM72,prompts ISCs to secretory lineages via upregulating peroxisome proliferator-activated receptorα(PPARα),thus maintaining intestinal epithelium integrity against noxious insults.Using genetic mouse models,we found that MG53 deficiency leads to exacerbated intestinal damage caused by various injuries in mice,whereas MG53 overexpression in ISCs is sufficient to ameliorate such damage.Mechanistically,MG53 promoted asymmetric division of ISCs to generate more progenitor cells of secretory lineages via activating PPARαsignaling.Specifically,MG53 overexpression induced PPARαexpression at transcriptional level and concomitantly increased PPARαactivity by elevating the contents of a panel of unsaturated fatty acids in the intestine that serve as potent endogenous agonists of PPARα.Furthermore,genetic ablation or pharmacological inhibition of PPARαabolished the protective effects of MG53.These findings reveal a crucial role of MG53-PPARαaxis in driving the secretory lineage commitment of ISCs,especially during injury response,highlighting the important therapeutic potential of targeting MG53-PPARαsignaling for IBD treatment and marking PPARαagonists as novel therapies for IBD caused by various etiologies.展开更多
Drosophila suzukii is a notorious pest which causes devastating damage to thin-skinned fruits,and the larvae feed on the fruit,causing extensive agricultural economic loss.The current application of insecticides to ma...Drosophila suzukii is a notorious pest which causes devastating damage to thin-skinned fruits,and the larvae feed on the fruit,causing extensive agricultural economic loss.The current application of insecticides to manage this pest results in serious resistance and environmental hazards,so an alternative strategy for D.suzukii biocontrol is urgently needed.Here,we reported that entomopathogenic Bacillus cereus has the potential to biocontrol D.suzukii.We isolated and identified the bacterial strain,B.cereus H1,that was detrimental to the fitness of both D.suzukii progenies and parents.D.suzukii was robustly repelled to depositing eggs on the halves with metabolites of B.cereus H1.Both males and females of D.suzukii were susceptible to B.cereus H1.B.cereus H1 significantly arrested larval development with at least 40%lethal larvae.The median lethal time(LT50)of males and females of D.suzukii challenged with B.cereus H1 was 3 and 2 d,respectively.Moreover,B.cereus H1 disrupted the intestinal integrity and pH value of D.suzukii and resulted in an increase in bacterial load of guts and hemolymph.Mechanistically,infection of B.cereus H1 led to the activation of the dual oxidase(DUOX)-ROS-Jun N-terminal kinase(JNK)pathway.The findings showed that the entomopathogen B.cereus H1 could potentially act as a biological control agent against D.suzukii,advancing fundamental concepts of integrated pest management programs against D.suzukii.展开更多
基金supported by Novus International Company (Missouri, USA)the earmarked fund for China Agricultural Research Systems (CARS-42)
文摘Background： Necrotic enteritis caused by Clostfidium perffingens infection leads to serious economic losses in the global poultry production. In the present study, we investigated the protective effects of essential oils （EO, which contained 25 % thymol and 25 % carvacrol as active components） supplementation on growth performance, gut lesions, intestinal morphology, and immune responses of the broiler chickens infected with C. perfringens. A total of 448 1-day-old male broiler chicks were allocated into eight treatment groups following a 4 x 2 factorial arrangement with four dietary EO dosages （0, 60, 120, or 240 mg/kg） and two infection status （with or without C. perfringens challenge from d 14 to 20）. Results： The challenge did not impair the growth performance of birds, but induced gut lesions and increased crypt depth in the ileum （P ≤ 0.05）. It also down-regulated the claudin-1 and occludin mRNA expression （P ≤0.05）, up-regulated the mRNA expression of interleukin-113 （P≤ 0.05）, tended to increase the toll-like receptor （TLR） 2 mRNA expression （P 〈 0.10） in the ileum, and enhanced the mucosal secretory IgA production （P 〈 0.05）. In the challenged birds, dietary EO supplementation linearly alleviated the gut lesions and improved the ratio of villus height to crypt depth （P ≤0.05）, and the supplementation of 120 and 240 mg/kg EO increased the serum antibody titers against Newcastle disease virus （P≤ 0.05）. Regardless of challenge, the EO supplementation showed a tendency to linearly elevate the feed conversion efficiency between 14 and 28 d of age as well as the occludin mRNA expression （P〈 0.10）, and linearly inhibited the mRNA expression of TLR2 and tumor necrotic factor-o in the ileum （P≤ 0.05）. Conclusions： The dietary supplementation of EO could alleviate the intestinal injury by improving intestinal integrity and modulating immune responses in the C. perffingens-challenged broiler chickens.
基金financially supported by the earmarked fund for the earmarked fund for CARS(CARS-45)National Science Fund for Distinguished Young Scholars of China(32425056)+1 种基金the National Key R&D Program of China(2023YFD2400600)Sichuan Innovation Team of National Modern Agricultural Industry Technology System(SCCXTD-2024-16).
文摘Background Cetobacterium somerae,a symbiotic microorganism resident in various fish intestines,is recognized for its beneficial effects on fish gut health.However,the mechanisms underlying the effects of C.somerae on gut health remain unclear.In this experiment,we investigated the influence of C.somerae(CGMCC No.28843)on the growth performance,intestinal digestive and absorptive capacity,and intestinal structural integrity of juvenile grass carp(Ctenopharyngodon idella)and explored its potential mechanisms.Methods A cohort of 2,160 juvenile grass carp with an initial mean body weight of 11.30±0.01 g were randomly allocated into 6 treatment groups,each comprising 6 replicates(60 fish per replicate).The experimental diets were supplemented with C.somerae at graded levels of 0.00(control),0.68×10^(9),1.35×10^(9),2.04×10^(9),2.70×10^(9),and 3.40×10^(9)cells/kg feed.Following a 10-week experimental period,biological samples were collected for subsequent analyses.Results Dietary supplementation with C.somerae at 1.35×10^(9)cells/kg significantly enhanced growth performance,intestinal development,and nutrient retention rate in juvenile grass carp(P<0.05).The treatment resulted in increased intestinal acetic acid concentration and enhanced activities of digestive enzymes and brush border enzymes(P<0.05).Furthermore,it reduced intestinal permeability(P<0.05),preserved tight junctions(TJ)ultrastructural integrity,and increased the expression of TJ and adherens junctions(AJ)biomarkers at both protein and transcriptional levels(P<0.05).Mechanistically,these effects may be correlated with enhanced antioxidant capacity and coordinated modulation of the RhoA/ROCK,Sirt1,and PI3K/AKT signaling pathways.The appropriate supplementation levels,based on weight gain rate,feed conversion ratio,the activity of serum diamine oxidase and the content of lipopolysaccharide,were 1.27×10^(9),1.27×10^(9),1.34×10^(9)and 1.34×10^(9)cells/kg,respectively.Conclusions C.somerae improved intestinal digestive and absorptive capacity of juvenile grass carp,maintained intestinal structural integrity,and thus promoted their growth and development.This work demonstrates the potential of C.somerae as a probiotic for aquatic animals and provides a theoretical basis for its utilization in aquaculture.
基金Supported by the National Natural Science Foundation of China,No.82060707 and No.82104381Application and Basis Research Project of Yunnan China,No.202201AW070016+2 种基金Central Special Fund for Guiding Local Science and Technology Development,No.202407AB110018Engineering Research Center of Yunnan Education Department,No.2022YGG03Open Research Fund Program of Yunnan Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment,No.2019DG016.
文摘BACKGROUND Kushenol I(KSCI)exhibits potential anti-inflammatory and antioxidant activities.However,its therapeutic effects and mechanisms in ulcerative colitis(UC)remain unclear.AIM To investigate the therapeutic effects and mechanisms of KSCI in alleviating UC.METHODS Therapeutic targets for KSCI in treating UC were identified using network pharmacology.Molecular docking and dynamics simulations confirmed the interactions between KSCI and these targets.In a murine UC model induced by dextran sodium sulfate(DSS),the anti-inflammatory and antioxidant effects of KSCI were evaluated following oral administration,as well as its impact on intestinal barrier function and immune response modulation.Finally,changes in gut microbiota composition were analyzed using 16S ribosomal RNA sequencing.RESULTS A total of 192 potential targets of KSCI in treating UC were identified using network pharmacology.KSCI bound stably to core targets including protein kinase B(AKT),p38 mitogen-activated protein kinase(p38 MAPK),NOD-like receptor thermal protein domain associated protein 3(NLRP3),phosphoinositide 3-kinase(PI3K),forkhead box O1(FOXO1),and Toll-like receptor 4(TLR4).The oral administration of KSCI improved colon length and body weight,and reduced disease activity in a mouse model of DSS-induced UC.KSCI suppressed pro-inflammatory cytokines(interleukin[IL-1β],IL-6,IL-17,and tumor necrosis factor alpha)and promoted the expression of the anti-inflammatory cytokine IL-10.It also inhibited key signaling molecules and modulated the expression of IL-1β,AKT,p38 MAPK,NLRP3,PI3K,AKT,FOXO1,and TLR4.KSCI exhibited potent antioxidant effects,ameliorating colonic inflammation and tissue damage.It improved intestinal barrier function,influenced gut microbiota composition,and increased splenic T-cell percentages.CONCLUSION KSCI alleviated DSS-induced UC by modulating gut microbiota,enhancing the intestinal barrier,reducing inflam-mation and oxidative stress,and regulating the immune response.
基金This research is supported by the Sichuan Science and Technology Program(No.2020YJ0398).
文摘Weaning stress can cause tight junctions damage and intestinal permeability enhancement,which leads to intestinal imbalance and growth retardation,thereby causing damage to piglet growth and development.Spermine can reduce stress.However,the mechanism of spermine modulating the intestinal integrity in pigs remains largely unknown.This study aims to examine whether spermine protects the intestinal barrier integrity of piglets through ras-related C3 botulinum toxin substrate 1(Rac1)/phospholipase C-g1(PLC-γ1)signaling pathway.In vivo,80 piglets were categorised into 4 control groups and 4 spermine groups(10 piglets per group).The piglets were fed with normal saline or spermine at 0.4 mmol/kg BW for 7 h and 3,6 and 9 d.In vitro,we investigated whether spermine protects the intestinal barrier after a tumor necrosis factor a(TNF-a)challenge through Rac1/PLC-γ1 signaling pathway.The in vivo study found that spermine supplementation increased tight junction protein mRNA levels and Rac1/PLC-γ1 signaling pathway gene expression in the jejunum of piglets.The serum D-lactate content was significantly decreased after spermine supplementation(P<0.05).The in vitro study found that 0.1 mmol/L spermine increased the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability(P<0.05).Further experiments demonstrated that spermine supplementation enhanced the levels of tight junction protein expression,Rac1/PLC-γ1 signaling pathway and transepithelial electrical resistance,and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-a challenge(P<0.05).Collectively,spermine protects intestinal barrier integrity through Rac1/PLC-γ1 signaling pathway in piglets.
基金supported by the National Natural Science Foundation of China(31772622)China Agriculture Research System(CARS-42-10)+2 种基金National Key R&D Program of China(2017YFD0502004)“111”project of Foreign Experts Affairs of ChinaSichuan Agricultural University 211 Foundation.
文摘Background:Consumption of resistant starch(RS)has been associated with various intestinal and systemic health benefits,but knowledge of its effects on intestinal health and inflammatory response in stressed birds is limited.Here,we examined how dietary RS supplementation from 12%raw potato starch(RPS)modulated inflammatory severity induced by lipopolysaccharide(LPS)in meat ducks.Results:LPS administration at 14,16,and 18 d(chronic challenge)decreased body weight(BW)and glucagon-like peptide 1 receptor(GLP-1R)level with higher intestinal permeability and inflammation,evident by higher proinflammatory cytokine levels.Dietary 12%RPS supplementation enhanced Claudin-1 and GLP-1R expression,along with lower levels of inflammatory factors in both ileum and serum.Microbiome analysis showed that RS treatment shifted microbial structure reflected by enriched the proportion of Firmicutes,Bifidobacterium,Ruminococcus,etc.Dietary RS addition also significantly increased the concentrations of propionate and butyrate during chronic LPS challenge.Furthermore,response to acute challenge,the ducks received 2 mg/kg BW LPS at 14 d had higher concentrations of serum endotoxins and inflammatory cytokines,as well as upregulated transcription of toll like receptor 4(TLR4)in ileum when compared to control birds.Analogous to GLP-1 agonist liraglutide,dietary RS addition decreased endotoxins and inflammation cytokines,whereas it upregulated the GLP-1 synthesis related genes expression.Meanwhile,dietary RS supplementation suppressed the acute LPS challenge-induced TLR4 transcription.Conclusions:These data suggest that dietary 12%RPS supplementation could attenuate the LPS-induced inflammation as well as intestinal injury of meat ducks,which might involve in the alteration in gut microbiota,SCFAs production and the signaling pathways of TLR4 and GLP-1/GLP-1R.
基金supported by the National Key Research and Development Program of China(2018YFD0500605)the Science and Technology Support Program of Sichuan Province(2014NZ0043,2016NZ0006)
文摘This experiment was conducted to investigate the effects of benzoic acid,Bacillus coagulans and oregano oil combined supplementation on growth performance,immune status and intestinal barrier integrity of piglets.In a 26-d experiment,25 piglets were randomly assigned to 5 treatments:1)a basal diet,negative control(NC),2)NC added with antibiotics,positive control(PC);3)NC added with benzoic acid at 3,000 g/t and Bacillus coagulans at 400 g/t(AB);4)NC added with benzoic acid at 3,000 g/t and o regano oil at 400 g/t(AO);5)NC added with 3,000 g/t benzoic acid and Bacillus coagulans at 400 g/t and oregano oil at 400 g/t(ABO);On d 27,all piglets were euthanized to obtain jejunal mucosa to measure immune status and intestinal barrier integrity.Results showed that pigs fed AB diet increased the final body weight and average daily body weight gain and decreased the ratio of feed to gain co mpared with NC group(P<0.05).Co mpared with NC group,AB,AO and ABO decreased serum tumor necrosis factor-a concentration and ABO decreased interleukin-1βconcentration in serum and jejunal mucosa(P<0.05).Compared with NC group,AB upregulated mRNA expressions of sodium-glucose cotransportel,claudin-1,occludin and mucin2 in jejunal mucosa and the populations of Bifidobacterium and Bacillus in cecal digesta(P<0.05).Compared with NC group,ABO increased jejunal mucosal occludin mRNA abundance and Bifidobacterium population in cecal digesta,and decreased Escherichia coli population in cecal digesta(P<0.05).Furthermore,AB and ABO increased Bacillus population in cecal digesta compared with PC group(P<0.05).These results indicated that dietary AB supplementation could improve growth performance and intestinal barrier integrity of piglets when fed antibiotic-free diets,which was possibly associated with the improvement of immune status and intestinal microflora.Dietary ABO supplementation is also beneficial to improve immune status and intestinal barrier integrity and micro flora of piglets.
基金Scientific Research(KAKENHI)(C),No.25460958Japan Society for the Promotion of Science,No.20K11513and Adaptable and Seamless Technology Transfer Program through target driven R&D from the Japan Agency for Medical Research and Development.
文摘BACKGROUND The gut-liver axis has attracted much interest in the context of chronic liver disease pathogenesis.Prebiotics such as dietary fibers were shown to attenuate non-alcoholic fatty liver disease(NAFLD)by modulating gut microbiota.Partially hydrolyzed guar gum(PHGG),a water-soluble dietary fiber,has been reported to alleviate the symptoms of various intestinal diseases and metabolic syndromes.However,its effects on NAFLD remain to be fully elucidated.To determine whether treatment with PHGG attenuates NAFLD development in mice through the gut-liver axis.METHODS Seven-week-old male C57BL/6J mice with increased intestinal permeability were fed a control or atherogenic(Ath)diet(a mouse model of NAFLD)for 8 wk,with or without 5%PHGG.Increased intestinal permeability was induced through chronic intermittent administration of low-dose dextran sulfate sodium.Body weight,liver weight,macroscopic findings in the liver,blood biochemistry[aspartate aminotransferase(AST)and alanine aminotransferase(ALT),total cholesterol,triglyceride,free fatty acids,and glucose levels],liver histology,myeloperoxidase activity in liver tissue,mRNA expression in the liver and intestine,serum endotoxin levels in the portal vein,intestinal permeability,and microbiota and short-chain fatty acid(SCFA)profiles in the cecal samples were investigated.RESULTS Mice with increased intestinal permeability subjected to the Ath diet showed significantly increased serum AST and ALT levels,liver fat accumulation,liver inflammatory(tumor necrosis factor-αand monocyte chemotactic protein-1)and fibrogenic(collagen 1a1 andαsmooth muscle actin)marker levels,and liver myeloperoxidase activity,which were significantly attenuated by PHGG treatment.Furthermore,the Ath diet combined with increased intestinal permeability resulted in elevated portal endotoxin levels and activated toll-like receptor(TLR)4 and TLR9 expression,confirming that intestinal permeability was significantly elevated,as observed by evaluating the lumen-to-blood clearance of fluorescein isothiocyanate-conjugated dextran.PHGG treatment did not affect fatty acid metabolism in the liver.However,it decreased lipopolysaccharide signaling through the gut-liver axis.In addition,it significantly increased the abundance of cecal Bacteroides and Clostridium subcluster XIVa.Treatment with PHGG markedly increased the levels of SCFAs,particularly,butyric acid,acetic acid,propionic acid,and formic acid,in the cecal samples.CONCLUSION PHGG partially prevented NAFLD development in mice through the gut-liver axis by modulating microbiota and downstream SCFA profiles.
文摘To evaluate the measurement of zonulin level and antibodies of zonulin and other tight junction proteins in the blood of controls and celiac disease patients.METHODSThis study was conducted to assess the variability or stability of zonulin levels vs IgA and IgG antibodies against zonulin in blood samples from 18 controls at 0,6,24 and 30 h after blood draw.We also measured zonulin level as well as zonulin,occludin,vinculin,aquaporin 4 and glial fibrillary acidic protein antibodies in the sera of 30 patients with celiac disease and 30 controls using enzyme-linked immunosorbent assay methodology.RESULTSThe serum zonulin level in 6 out of 18 subjects was low or<2.8 ng/mL and was very close to the detection limit of the assay.The other 12 subjects had zonulin levels of>2.8 ng/mL and showed significant fluctuation from sample to sample.Comparatively,zonulin antibody measured in all samples was highly stable and reproducible from sample to sample.Celiac disease patients showed zonulin levels with a mean of 8.5 ng/mL compared to 3.7 ng/mL in controls(P<0.0001).Elevation of zonulin level at 2SD above the mean was demonstrated in 37%of celiac disease patients,while antibodies against zonulin,occludin and other tight junction proteins was detected in up to 86%of patients with celiac disease.CONCLUSIONDue to its fluctuation,a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity.Measurement of IgG and IgA antibodies against zonulin,occludin,and other tight junction proteins is proposed for the evaluation of the loss of intestinal barrier integrity.
基金funded by National Key R&D Program of China(2022YFA1303003,2018YFA0800701,2018YFA0507603,and 2018YFA0800501)National Natural Science Foundation of China(81770376,81630008,81790621,31521062,31671177,and 81370234).
文摘Emerging evidence suggests that priming intestinal stem cells(ISCs)towards secretory progenitor cells is beneficial for maintaining gut homeostasis against inflammatory bowel disease(IBD).However,the mechanism driving such biased lineage commitment remains elusive.Here we show that MG53,also named as TRIM72,prompts ISCs to secretory lineages via upregulating peroxisome proliferator-activated receptorα(PPARα),thus maintaining intestinal epithelium integrity against noxious insults.Using genetic mouse models,we found that MG53 deficiency leads to exacerbated intestinal damage caused by various injuries in mice,whereas MG53 overexpression in ISCs is sufficient to ameliorate such damage.Mechanistically,MG53 promoted asymmetric division of ISCs to generate more progenitor cells of secretory lineages via activating PPARαsignaling.Specifically,MG53 overexpression induced PPARαexpression at transcriptional level and concomitantly increased PPARαactivity by elevating the contents of a panel of unsaturated fatty acids in the intestine that serve as potent endogenous agonists of PPARα.Furthermore,genetic ablation or pharmacological inhibition of PPARαabolished the protective effects of MG53.These findings reveal a crucial role of MG53-PPARαaxis in driving the secretory lineage commitment of ISCs,especially during injury response,highlighting the important therapeutic potential of targeting MG53-PPARαsignaling for IBD treatment and marking PPARαagonists as novel therapies for IBD caused by various etiologies.
基金supported by the National Natural Science Foundation of China(31501175)Grants of Anhui Natural Science Foundation(20230302123239)Talent Grants of Anhui Agricultural University(RC342201).
文摘Drosophila suzukii is a notorious pest which causes devastating damage to thin-skinned fruits,and the larvae feed on the fruit,causing extensive agricultural economic loss.The current application of insecticides to manage this pest results in serious resistance and environmental hazards,so an alternative strategy for D.suzukii biocontrol is urgently needed.Here,we reported that entomopathogenic Bacillus cereus has the potential to biocontrol D.suzukii.We isolated and identified the bacterial strain,B.cereus H1,that was detrimental to the fitness of both D.suzukii progenies and parents.D.suzukii was robustly repelled to depositing eggs on the halves with metabolites of B.cereus H1.Both males and females of D.suzukii were susceptible to B.cereus H1.B.cereus H1 significantly arrested larval development with at least 40%lethal larvae.The median lethal time(LT50)of males and females of D.suzukii challenged with B.cereus H1 was 3 and 2 d,respectively.Moreover,B.cereus H1 disrupted the intestinal integrity and pH value of D.suzukii and resulted in an increase in bacterial load of guts and hemolymph.Mechanistically,infection of B.cereus H1 led to the activation of the dual oxidase(DUOX)-ROS-Jun N-terminal kinase(JNK)pathway.The findings showed that the entomopathogen B.cereus H1 could potentially act as a biological control agent against D.suzukii,advancing fundamental concepts of integrated pest management programs against D.suzukii.
