Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clost...Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.展开更多
Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify...Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.展开更多
We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution...We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin's valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.展开更多
Objective:To test the curative effect of human umbilical cord-derived mesenchymal stem cells on rat acute radioactive enteritis and thus in provide clinical therapeutic basis for radiation sickness.Methods:Human umbil...Objective:To test the curative effect of human umbilical cord-derived mesenchymal stem cells on rat acute radioactive enteritis and thus in provide clinical therapeutic basis for radiation sickness.Methods:Human umbilical cord-derived mesenchymal stem cells were cultivated in vitro and the model of acute radioactive enteritis of rats was established.Then,the umbilical cord mesenchymal stem cells were injected into the rats via tail vein.Visual and histopathiological changes of the experimental rats were observed.Results:After the injection,the rats in the prevention group and treatment group had remarkably better survival status than those in the control group.The histological observations revealed that the former also had better intestinal mucosa structure,more regenerative cells and stronger proliferation activity than the latter.Conclusions:Human umbilical cord-derived mesenchymal stem cells have a definite therapeutic effect on acute radioactive enteritis in rats.展开更多
BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nu...BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.展开更多
Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in ...Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear.In this study,we aimed to investigate the effects of different doses of tannic acid on the production performance,immunity,and intestinal health of broilers by constructing an NE model with C.perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.Results Challenged birds showed significant reduction in body weight,villus height,and the ratio of villus height to crypt depth(P<0.05)and increase in the feed consumption gain ratio,intestinal lesion score,and crypt depth(P<0.05).The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance(P<0.05)and increased the ratio of Firmicutes/Bacteroidota and cecal content of C.perfringens(P<0.05).Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels(P<0.05).Addi-tion of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C.perfringens in the cecum.Specifically,tannic acid reduced the serum levels of C reactive protein,myeloperoxidase,and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds.NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna,Thermoanaerobacterium,and Thermosinus abundance(P<0.05);their microbial composition and functional predictions were similar to those of the NC group.Conclusions Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function.The recommended dietary tannic acid additive level is 500–750 mg/kg.Our study findings would be useful in reducing related economic losses in the broiler industry.展开更多
Background:The ban of in-feed antimicrobial additives has negatively affected the poultry industry by causing necrotic enteritis(NE)to emerge in the flocks.Alternatives such as Bacillus probiotics have shown to be eff...Background:The ban of in-feed antimicrobial additives has negatively affected the poultry industry by causing necrotic enteritis(NE)to emerge in the flocks.Alternatives such as Bacillus probiotics have shown to be effective on eliminating the negative effects of this disease.Two experiments were conducted to investigate the effect of Bacillus amyloliquefaciens CECT 5940(BA)in broiler chickens under NE challenge and/or fed diets with different protein levels.Methods:In both experiments,480 day-old mix-sexed Ross-308 broilers were arranged in a 2×2 factorial arrangement of treatments.In experiment 1,the factors were NE challenge(yes or no)and probiotic(yes or no).In experiment 2,the factors were dietary crude protein levels(standard or reduced)and probiotic(yes or no)and were used under NE challenge condition.Oral administration of Eimeria oocysts(day 9)followed by inoculation with Clostridium perfringens(day 14 and 15)was used to induce NE challenge.On day 16,two birds from each treatment were gavaged with fluorescein isothiocyanate-dextran(FITC-d)and blood samples were collected for gut integrity evaluation,and jejunal samples were collected for gene expression assay.Results:In experiment 1,BA supplementation decreased caspase-3(CASP3)(P<0.001)and caspase-8(CASP8)(P<0.05)and increased occludin(OCLD)(P<0.05)expression regardless of the challenge.Additionally,BA supplementation downregulated interfron-γ(IFN-γ)expression(P<0.01)and upregulated immunoglobulin-G(IgG)(P<0.01)and immunoglobulin-M(IgM)(P<0.05)only in challenged birds.In experiment 2,the expression of genes encoding mucin-2(MUC2)(P<0.001),tight junction protein-1(TJP1)(P<0.05)and OCLD(P<0.05)were upregulated by the addition of BA in the diet,regardless of the crude protein level.Further,BA supplementation downregulated INF-γ(P<0.01)and upregulated immunoglobulin-A(IgA)(P<0.05),IgM(P<0.05)and IgG(P<0.01)regardless of the crude protein level.Conclusion:These findings suggest that supplementation of BA in broiler diets can improve gut health by modulation of genes related to the mucosal barrier,tight junction,and immunity in broilers challenged by unfavourable conditions such as NE challenge.展开更多
Background:The emergence of antimicrobial resistance has necessitated the development of effective alternatives to antibiotics for livestock and poultry production.This study investigated a possible synergy between bu...Background:The emergence of antimicrobial resistance has necessitated the development of effective alternatives to antibiotics for livestock and poultry production.This study investigated a possible synergy between butyrate and forskolin(a natural labdane diterpene)in enhancing innate host defense,barrier function,disease resistance,growth performance,and meat quality of broilers.Methods:The expressions of representative genes involved in host defense(AvBD9 and AvBD10),barrier function(MUC2,CLDN1,and TJP1),and inflammation(IL-1β)were measured in chicken HD11 macrophages in response to butyrate and forskolin in the presence or absence of bacterial lipopolysaccharides(LPS).Intestinal lesions and the Clostridium perfringens titers were also assessed in C.perfringens-challenged chickens fed butyrate and forskolincontaining Coleus forskohlii(CF)extract individually or in combination.Furthermore,growth performance and carcass characteristics were evaluated in broilers supplemented with butyrate and the CF extract for 42 d.Results:Butyrate and forskolin synergistically induced the expressions of AvBD9,AvBD10,and MUC2 in chicken HD11 cells(P<0.05)and the synergy was maintained in the presence of LPS.Butyrate and forskolin also suppressed LPS-induced IL-1βgene expression in HD11 cells in a synergistic manner(P<0.05).The two compounds significantly reduced the intestinal lesions of C.perfringens-challenged chickens when combined(P<0.05),but not individually.Furthermore,butyrate in combination with forskolin-containing CF extract had no influence on weight gain,but significantly reduced feed intake(P<0.05)with a strong tendency to improve feed efficiency(P=0.07)in a 42-d feeding trial.Desirably,the butyrate/forskolin combination significantly decreased abdominal fat deposition(P=0.01)with no impact on the carcass yield,breast meat color,drip loss,or pH of d-42 broilers.Conclusions:Butyrate and forskolin has potential to be developed as novel antibiotic alternatives to improve disease resistance,feed efficiency,and carcass composition of broilers.展开更多
Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts...Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts(LTE),containing chlorogenic acid and curcumin,have been reported to possess anti-inflammatory,and antioxidant properties.Based on these potential biological benefits,this study aims to investigate the reparative effects of LTE on the intestinal barrier dysfunction in NE-infected broilers and assess its therapeutic efficacy in alleviating SLI.By elucidating the regulatory mechanisms of LTE on gut-liver axis health,this research provides new insights into the prevention and treatment of NE in broilers.Results LTE improved body weight and average daily gain while reducing intestinal lesion scores,coccidia oocysts,and Clostridium perfringens counts in NE broilers(P<0.05).LTE enhanced intestinal morphology and up-regulated the expression of tight junction protein genes(CLDN1,TJP1)and MUC2,suppressed pro-inflammatory cytokine and myeloperoxidase(MPO)levels,and minimized endotoxin(ET)accumulation in NE broilers(P<0.05).Furthermore,LTE alleviated oxidative stress in ileal cells and protected mitochondrial structure and function in NE broilers.NE infection induced intestinal permeability in broilers,leading to increased serum pro-inflammatory cytokines and intestinal-derived endotoxin levels,which caused liver damage.LTE significantly reduced liver pathologic damage,pro-inflammatory cytokine levels,aspartate transaminase,alanine aminotransferase,and ROS levels in NE broilers(P<0.05).Additionally,16S rRNA sequencing revealed that NE significantly increased the relative abundance of Barnesiella and decreased the relative abundance of Bacteroidota,Desulfobacterota and Bacteroides in the cecum of broilers.LTE enhanced intestinal microbiota diversity and reduced the segregation of intestinal microbiota induced by NE infection.Conclusions In summary,LTE can alleviate NE and SLI by modulating the microbiota,inhibiting inflammation and oxidative stress,and ameliorating mitochondrial dysfunction,thereby enhancing gut-liver axis health and growth performance.展开更多
Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV in...Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.展开更多
BACKGROUND With programmed death-1(PD-1) inhibitors becoming the standard treatment for lung cancer,PD-1-related adverse reactions and treatment have gradually become prominent.CASE SUMMARY First reported case of tisl...BACKGROUND With programmed death-1(PD-1) inhibitors becoming the standard treatment for lung cancer,PD-1-related adverse reactions and treatment have gradually become prominent.CASE SUMMARY First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles.The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms,abdominal computed tomography and colonoscopy improved,significant diarrhea was not occurred.CONCLUSION Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.展开更多
Background The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE)caused by Clostridium perfringens.Methods The aim of this study was to investigate the effects of d...Background The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE)caused by Clostridium perfringens.Methods The aim of this study was to investigate the effects of dietary supplementation with Macleaya cordata extract(MCE)on the immune function and gut microbiota of broilers with NE.A total of 2881-day-old broiler chicks were randomly assigned to a 2×2 factorial arrangement with two concentrations of dietary MCE supplementation(0 or 350 mg/kg of diet)and two disease challenge statuses(control or NE).Results The results revealed that NE significantly increased the feed conversion rate(FCR),mortality,intestinal lesion score,the levels of IL-1β,IL-17 and IFN-γ/IL-4 in serum and IL-17/IL-10 in the jejunal mucosa,m RNA levels of TLR2,IFN-γand p Ig R in the jejunum,and Clostridium perfringens concentrations in the cecum.NE significantly decreased the body weight(BW),body weight gain(BWG),jejunal villus height,V/C,m RNA level of AMPK-α1 in jejunum,IL-4 level in the jejunal mucosa and lactic acid bacteria abundance in the cecum.MCE significantly increased BW,BWG,jejunal villus height,V/C,m RNA levels of occludin,ZO-1 and AMPK-α1 in the jejunum,the levels of Ig A and Ig G in serum and IL-10 in the jejunal mucosa and m RNA levels of NF-κB,IL-10 and MHC-II in the jejunum.Additionally,MCE significantly decreased the FCR,mortality,intestinal lesion score,jejunal crypt depth,the levels of IFN-γand IL-17 in serum and IL-17/IL-10 in the jejunal mucosa,Clostridium perfringens concentrations in the cecum,and m RNA levels of IL-17/IL-10 in the jejunum.Moreover,NE significantly increased the abundance of bacteria that are associated with inflammation,obesity and depression(Alistipes,Barnesiella,Intestinimonas,RF39 and UCG-005)and significantly decreased the abundance of short-chain fatty acid(SCFA)-producing bacteria(Anaerotruncus,Butyricicoccus and Bacteroides)in the cecum.MCE significantly increased the abundance of SCFA-producing bacteria(Streptococcus,Ruminococcus_torques_group and Lachnospiraceae_NK4A136_group)and significantly reduced the abundance of bacteria that are associated with inflammation and obesity(Alistipes,Barnesiella and UCG-010)in the cecum.In the cecum of broilers with NE,the relative abundance of Barnesiella and Alistipes was higher and that of Lachnoclostridium and Shuttleworthia was lower.Interestingly,these trends were reversed by the addition of MCE to the diet.Spearman correlation analysis showed that Barnesiella and Alistipes were associated with enhanced intestinal inflammation and inhibited growth performance,whereas Lachnoclostridium and Shuttleworthia were associated with anti-inflammatory effects.Conclusions MCE ameliorated the loss of growth performance in broiler chickens with NE,probably by regulating the intestinal barrier,immune function,and gut microbiota.展开更多
Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism in...Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.展开更多
Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based...Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis,but its colonizing and therapeutic efficacy after oral administration are limited.Here,we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein(MMPB)with the famous probiotic bacteria Lactobacillus plantarum(Lac)and Bifidobacterium animalis subsp.lactis(Bif).The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein.Owing to presence of the artificial protein on the MMPB surface,the nanodrug strongly bound and cross-linked the probiotic cells,forming the Lac+Bif+MMPB co-assembly.During co-incubation with the kanamycin-resistant E.coli strain(Ecka),the co-assembly strongly reduced the viability of Ecka,leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2.After oral administration of the co-assembly to themice pre-colonized by Ecka,Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine,and led to 2-3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif.More importantly,in the mice suffering from enteritis caused by drug-resistant S.Tm,the co-assembly remarkably recovered the mouse body weight,reduced intestine colonization of S.Tm cells,and decreased the levels of pro-inflammatory cytokines in both serum and colons.This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.展开更多
Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferat...Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferation,the precise underlying mechanisms are unclear.Objective This study integrated transcriptomics and metabolomics to systematically investigate the mechanism by which tannins,specifically pentagalloylglucose(PGG)and tannic acid(TA),inhibit C.perfringens and potential pathways to alleviate infection in vivo.Results Ion concentration measurements,flow cytometric analysis,and transmission electron microscopy revealed that PGG and TA damaged the cell membrane structure of C.perfringens,triggering cytoplasmic content leakage.Additionally,PGG and TA significantly affected C.perfringens at the transcriptional and metabolic levels.Bioinformatics analysis revealed that PGG and TA induced amino acid restriction,disrupted energy metabolism,and impeded the ability of C.perfringens to sense and respond to the external environment.In an in vitro C.perfringens-infected intestinal cell model,PGG and TA boundαtoxin,significantly reduced the mRNA expression of inflammatory factors,and improved intestinal barrier function and cell viability.Compared to PGG,TA exhibited stronger inhibitory activity against C.perfringens and binding toαtoxin.In vivo,PGG and TA alleviated C.perfringens-induced weight loss in mice,improved intestinal villi morphology,and reduced intestinal inflammation and tight junction gene dysregulation.Conclusion These findings indicate that tannins inhibit C.perfringens,improve gut tissue integrity and reduce inflammation,demonstrating their multi-target effects of resisting intestinal diseases caused by harmful bacteria.This offers new insights for plant polyphenol-based strategies against necrotic enteritis.展开更多
Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regul...Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regulatory effect on the structure of intestinal flora,providing clinical evidence for the integrated traditional Chinese and Western medicine treatment of radiation enteritis.Methods:A total of 40 patients with radiation enteritis admitted to the Oncology Department of Linfen Central Hospital from September 2023 to December 2024 were selected and divided into an observation group and a control group according to the random number table method,with 20 cases in each group.The control group was treated with Clostridium butyricum live capsules,while the observation group was treated with Modified Gegen Qinlian Decoction in addition to the treatment given to the control group.Both groups received a 4-week treatment course.Intestinal function indicators and changes in intestinal flora structure were compared between the two groups before and after treatment,and clinical efficacy was evaluated.Results:After 4 weeks of treatment,the total effective rate in the observation group versus the control group was(95.00%vs 65.00%),with a statistically significant difference(P<0.05).The fecal formation rate in the observation group(85.00%vs 60.00%)was significantly higher than that in the control group,and the defecation frequency(2.15±0.42 vs 3.85±0.65)times/day was significantly lower than that in the control group,with statistically significant differences(P<0.05).After treatment,the quantities of Bifidobacterium(6.85±0.72 L vs 5.23±0.61 L)gCFU/g and Lactobacillus(6.52±0.68 L vs 4.98±0.57 L)gCFU/g in the observation group were significantly higher than those in the control group,while the quantities of Escherichia coli(4.12±0.53 L vs 5.67±0.65 L)gCFU/g and Staphylococcus(3.85±0.48 L vs 5.23±0.59 L)gCFU/g were significantly lower than those in the control group,with statistically significant differences(P<0.05).Conclusion:Clinical studies have confirmed that the synergistic treatment of radiation enteritis with Modified Gegen Qinlian Decoction and probiotics can significantly improve patients’clinical symptoms and restore the balance of intestinal flora,providing an effective regimen for clinical treatment.展开更多
BACKGROUND Radiation enteritis is a common complication of radiation therapy in which the surrounding normal intestinal tissue is damaged by ionising radiation,and there is no standard pharmacological prophylaxis or t...BACKGROUND Radiation enteritis is a common complication of radiation therapy in which the surrounding normal intestinal tissue is damaged by ionising radiation,and there is no standard pharmacological prophylaxis or treatment regimen available.Mesenchymal stem cell transplantation can be used for radiation protection and the treatment of acute radiation injury,but its therapeutic mechanism of action remains unclear.AIM To investigate the protective effects of autologous bone marrow-derived mesenchymal stem cell(ABMSC)transplantation on radiation-induced intestinal injury.METHODS A model of acute radioactive enteritis was established in dogs by applying abdominal intensity-modulated radiation at a single X-ray dose of 12 Gy.ABMSCs were transplanted into the mesenteric artery with the technology of femoral artery puncture and DSA imaging two days after radiation.Visual and histopathological changes of the experimental dogs were observed.Different kinds of cytokines from intestinal samples were tested using Quantibody Canine Cytokine Array method.Enzyme-linked immunosorbent assay(ELISA)was also used to evaluate the cytokines changes in serum.RESULTS The ABMSCs group showed significant improvements in survival status compared with the blank and saline treatment groups.Histological observations revealed that the former had lower histological scores than the later after treatment(P<0.05).Compared to the control groups,interleukin(IL)-10 and monocyte chemotactic protein(MCP)-1 from intestinal samples showed a remarkable increase and ELISA of serum samples proved higher secretion of the two target cytokines in the ABMSCs group(P<0.05).CONCLUSION Our data suggest that transplantation of ABMSCs promotes intestinal recovery after acute radioactive injury in Beagle dogs.The cytokines of IL-10 and MCP-1 might play an important role in this process.展开更多
Objective:To evaluate the clinical efficacy of cefixime(Cef)combined with montmorillonite powder(MP)in treating pediatric bacterial enteritis.Methods:Seventy-two cases of bacterial enteritis in children admitted betwe...Objective:To evaluate the clinical efficacy of cefixime(Cef)combined with montmorillonite powder(MP)in treating pediatric bacterial enteritis.Methods:Seventy-two cases of bacterial enteritis in children admitted between October 2021 and October 2023 were selected and randomly divided into two groups.The combination group received Cef treatment alongside MP,while the control group received only Cef treatment.The groups were compared based on overall efficacy,symptom relief time,and other indicators.Results:The combination group showed a higher overall efficacy,shorter symptom relief time,lower levels of inflammatory markers post-treatment,and a higher proportion of normal and grade I dysbiosis in the intestinal flora,with significant differences compared to the control group(P<0.05).Conclusion:Cef combined with MP is significantly effective in treating pediatric bacterial enteritis,promoting symptom relief,reducing inflammation,and correcting intestinal flora imbalance.展开更多
Background:Two experiments were conducted to establish an optimal NE challenge model and evaluate the efficacy of stimbiotic(STB)supplementation in necrotic enteritis(NE)challenged broilers.In Exp.1,a total of 120 Arb...Background:Two experiments were conducted to establish an optimal NE challenge model and evaluate the efficacy of stimbiotic(STB)supplementation in necrotic enteritis(NE)challenged broilers.In Exp.1,a total of 120 Arbor Acres(AA)broilers(45.0±0.21 g)were randomly assigned to 6 treatments in a 3×2 factorial arrangement.Vaccine treatments included non-challenge(0),×10 the recommended dose(×10)or×20 the recommended dose(×20)by the manufacturer.Clostridium perfringens(CP)treatments were non-challenge(No)or 3 mL of 2.2×10^(7)CFU CP challenge(Yes).In Exp.2,a total of 72 AA broilers(40.17±0.27 g)were randomly assigned to 6 treatments in a 3×2 factorial arrangement.Dietary treatments included non-additive(CON),100 mg/kg STB(STB)and 100 mg/kg STB on top of a typical commercial blend including an essential oil,probiotics,and enzyme(CB).Challenge treatments included non-NE challenge(No)and NE challenge(Yes)as established in Exp.1.Results:In Exp.1,CP and vaccine challenge decreased(P<0.05)body weight(BW),body weight gain(BWG)and feed intake(FI),and increased(P<0.05)the number of broilers with diarrhea and intestinal lesions.The oral administration of×20 recommended dose of vaccines coupled with 3 mL of 2.2×10^(7)CFU CP resulted in(P<0.01)a significantly increased incidence of wet litter and intestinal lesions.Thus,this treatment was chosen as the challenge model for the successful inducement of NE in Exp.2.In Exp.2,the NE challenge negatively affected(P<0.01)growth performance,ileal morphology,immunoglobulin contents in blood,caecal microbiota in the caecum,footpad dermatitis,intestinal lesion scores,tumour necrosis factor(TNF-α)and endotoxin in the serum compared with the non-NE challenged birds.The supplementation of STB and CB in diets enhanced(P<0.05)growth performance,intestinal microbiota,and blood profiles by stimulating ileal morphology(VH and VH:CD)and propionate production in the cecum,and there were no differences in measured variables between STB and CB supplemented birds.Conclusion:Overall,these results indicate that STB supplementation was able to reduce the inflammatory response and improve the performance of NE challenged birds,and the supplementation of STB alone was as effective as a typical commercial blend containing a number of other additives.展开更多
Objective:To explore the effectiveness of early enteral nutrition therapy in ICU patients with respiratory failure.Methods:A total of 76 ICU patients with respiratory failure,admitted from May 2024 to May 2025,were in...Objective:To explore the effectiveness of early enteral nutrition therapy in ICU patients with respiratory failure.Methods:A total of 76 ICU patients with respiratory failure,admitted from May 2024 to May 2025,were included in the study.They were divided into an observation group and a control group using a random number table method,and relevant treatment indicators were compared.Results:The total effective rate in the observation group was higher than that in the control group(p<0.05).After treatment,the observation group showed superior lung function,organ function,health status,nutritional status,body mass index,and blood gas analysis indicators compared to the control group(p<0.05).Conclusion:Early enteral nutrition therapy is effective in treating ICU patients with respiratory failure and is beneficial for improving their lung function,nutritional status,and blood gas parameters,making it worthy of promotion.展开更多
基金supported by China Agriculture Research System Program(Project No.CARS-41-G04)。
文摘Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.
基金support for the project was provided by Chicken Farmers of Saskatchewan(424357)Canadian Poultry Research Council(424854)+1 种基金Natural Sciences and Engineering Research Council of Canada(424679)Saskatchewan Agriculture Development Fund(426954).
文摘Background Necrotic enteritis(NE)is an economically important disease of broiler chickens caused by Clostridium perfringens(CP).The pathogenesis,or disease process,of NE is still not clear.This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investi-gate the possible variations in the metabolic profile of birds infected with different isolates of CP.Methodology Using a well-established NE model,the protein content of feed was changed abruptly before expos-ing birds to CP isolates with different toxin genes combinations(cpa,cpb2,netB,tpeL;cpa,cpb2,netB;or cpa,cpb2).Metabolomics analysis of jejunal contents was performed by a targeted,fully quantitative LC-MS/MS based assay.Results This study detected statistically significant differential expression of 34 metabolites including organic acids,amino acids,fatty acids,and biogenic amines,including elevation of butyric acid at onset of NE in broiler chickens.Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an eleva-tion of butyric acid consistently among 21 differentially expressed metabolites including organic acids,amino acids,and biogenic amines,underscoring its potential role during the development of NE.Furthermore,protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.Conclusion This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens.Among all the metabolites,butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers.Logistic regression analysis revealed a positive association between butyric acid(coefficient:1.23,P<0.01)and CP infection,while showing a negative association with amino acid metabolism.These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level.Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE,regardless of predisposing factors.
文摘We present the case of a 29-year-old patient with a history of abdominal pain and vomiting.Based on wireless video capsule findings he was previously diagnosed with ileal Crohn's disease at a different institution,although the clinical and radiological picture was not typical and the response to corticosteroids was poor.We performed a single-balloon enteroscopy showing a short,ulcerous stenosis 50 cm proximal from Bauhin's valve.The endoscopic and clinical histopathological findings were compatible with cryptogenic multifocal ulcerous stenosing enteritis(CMUSE).High dose corticosteroids were again started,without effect.The monoclonal tumor necrosis factor-α(TNF-α) antibody infliximab was added to the medical therapy.After induction therapy,both clinical and endoscopic amelioration was obtained.Larger case studies are needed to confirm the efficacy of TNF-α inhibition in steroid refractory CMUSE.
基金supported by Wu Zuze Science and Technology Development Foundation of Beijing
文摘Objective:To test the curative effect of human umbilical cord-derived mesenchymal stem cells on rat acute radioactive enteritis and thus in provide clinical therapeutic basis for radiation sickness.Methods:Human umbilical cord-derived mesenchymal stem cells were cultivated in vitro and the model of acute radioactive enteritis of rats was established.Then,the umbilical cord mesenchymal stem cells were injected into the rats via tail vein.Visual and histopathiological changes of the experimental rats were observed.Results:After the injection,the rats in the prevention group and treatment group had remarkably better survival status than those in the control group.The histological observations revealed that the former also had better intestinal mucosa structure,more regenerative cells and stronger proliferation activity than the latter.Conclusions:Human umbilical cord-derived mesenchymal stem cells have a definite therapeutic effect on acute radioactive enteritis in rats.
文摘BACKGROUND: This study aimed to explore the risk factors associated with intensive care unitacquired weakness(ICU-AW) in critically ill patients at risk of malnutrition and to evaluate the efficacy of early enteral nutrition(EEN) and the role of biomarkers in managing ICU-AW.METHODS: This retrospective, observational cohort study included 180 patients at risk of malnutrition admitted to the emergency intensive care unit of the First Affiliated Hospital of Xiamen University Hospital from January 2022 to December 2023. Patients were divided into ICU-AW group and non-ICU-AW group according to whether they developed ICU-AW, or categorized into EEN and parenteral nutrition(PN) groups according to nutritional support. ICU-AW was diagnosed using the Medical Research Council score. The primary outcome was the occurrence of ICU-AW.RESULTS: The significant factors associated with ICU-AW included age, sex, type of nutritional therapy, mechanical ventilation(MV), body mass index(BMI), blood urea nitrogen(BUN), and creatinine(Cr) levels(P<0.05). The PN group developed ICU-AW earlier than did the EEN group, with a significant difference observed(log-rank P<0.001). Among biomarkers for ICU-AW, the mean prealbumin(PAB)/C-reactive protein(CRP) ratio had the highest diagnostic accuracy(area under the curve [AUC] 0.928, 95% confidence interval [95% CI] 0.892–0.946), surpassing the mean Cr/BUN ratio(AUC 0.740, 95% CI 0.663–0.819) and mean transferrin levels(AUC 0.653, 95% CI 0.574–0.733).CONCLUSION: Independent risk factors for ICU-AW include female sex, advanced age, PN, MV, lower BMI, and elevated BUN and Cr levels. EEN may potentially delay ICU-AW onset, and the PAB/CRP ratio may be an effective diagnostic marker for this condition.
基金the China Agriculture Research System program(CARS-41-G11).
文摘Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear.In this study,we aimed to investigate the effects of different doses of tannic acid on the production performance,immunity,and intestinal health of broilers by constructing an NE model with C.perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.Results Challenged birds showed significant reduction in body weight,villus height,and the ratio of villus height to crypt depth(P<0.05)and increase in the feed consumption gain ratio,intestinal lesion score,and crypt depth(P<0.05).The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance(P<0.05)and increased the ratio of Firmicutes/Bacteroidota and cecal content of C.perfringens(P<0.05).Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels(P<0.05).Addi-tion of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C.perfringens in the cecum.Specifically,tannic acid reduced the serum levels of C reactive protein,myeloperoxidase,and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds.NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna,Thermoanaerobacterium,and Thermosinus abundance(P<0.05);their microbial composition and functional predictions were similar to those of the NC group.Conclusions Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function.The recommended dietary tannic acid additive level is 500–750 mg/kg.Our study findings would be useful in reducing related economic losses in the broiler industry.
基金supported by grants of Evonik Nutrition&Care GmbH,Germany.
文摘Background:The ban of in-feed antimicrobial additives has negatively affected the poultry industry by causing necrotic enteritis(NE)to emerge in the flocks.Alternatives such as Bacillus probiotics have shown to be effective on eliminating the negative effects of this disease.Two experiments were conducted to investigate the effect of Bacillus amyloliquefaciens CECT 5940(BA)in broiler chickens under NE challenge and/or fed diets with different protein levels.Methods:In both experiments,480 day-old mix-sexed Ross-308 broilers were arranged in a 2×2 factorial arrangement of treatments.In experiment 1,the factors were NE challenge(yes or no)and probiotic(yes or no).In experiment 2,the factors were dietary crude protein levels(standard or reduced)and probiotic(yes or no)and were used under NE challenge condition.Oral administration of Eimeria oocysts(day 9)followed by inoculation with Clostridium perfringens(day 14 and 15)was used to induce NE challenge.On day 16,two birds from each treatment were gavaged with fluorescein isothiocyanate-dextran(FITC-d)and blood samples were collected for gut integrity evaluation,and jejunal samples were collected for gene expression assay.Results:In experiment 1,BA supplementation decreased caspase-3(CASP3)(P<0.001)and caspase-8(CASP8)(P<0.05)and increased occludin(OCLD)(P<0.05)expression regardless of the challenge.Additionally,BA supplementation downregulated interfron-γ(IFN-γ)expression(P<0.01)and upregulated immunoglobulin-G(IgG)(P<0.01)and immunoglobulin-M(IgM)(P<0.05)only in challenged birds.In experiment 2,the expression of genes encoding mucin-2(MUC2)(P<0.001),tight junction protein-1(TJP1)(P<0.05)and OCLD(P<0.05)were upregulated by the addition of BA in the diet,regardless of the crude protein level.Further,BA supplementation downregulated INF-γ(P<0.01)and upregulated immunoglobulin-A(IgA)(P<0.05),IgM(P<0.05)and IgG(P<0.01)regardless of the crude protein level.Conclusion:These findings suggest that supplementation of BA in broiler diets can improve gut health by modulation of genes related to the mucosal barrier,tight junction,and immunity in broilers challenged by unfavourable conditions such as NE challenge.
基金supported by the USDA National Institute of Food and Agriculture (grant no. 2018–68003-27462 and 2020–67016-31619)Oklahoma Center for the Advancement of Science and Technology (grant no. AR19–027)+2 种基金Boulware Endowment FundOklahoma Agricultural Experiment Station Project H-3112supported by the USDA-NIFA Predoctoral Fellowship grant 2018–67011-28041
文摘Background:The emergence of antimicrobial resistance has necessitated the development of effective alternatives to antibiotics for livestock and poultry production.This study investigated a possible synergy between butyrate and forskolin(a natural labdane diterpene)in enhancing innate host defense,barrier function,disease resistance,growth performance,and meat quality of broilers.Methods:The expressions of representative genes involved in host defense(AvBD9 and AvBD10),barrier function(MUC2,CLDN1,and TJP1),and inflammation(IL-1β)were measured in chicken HD11 macrophages in response to butyrate and forskolin in the presence or absence of bacterial lipopolysaccharides(LPS).Intestinal lesions and the Clostridium perfringens titers were also assessed in C.perfringens-challenged chickens fed butyrate and forskolincontaining Coleus forskohlii(CF)extract individually or in combination.Furthermore,growth performance and carcass characteristics were evaluated in broilers supplemented with butyrate and the CF extract for 42 d.Results:Butyrate and forskolin synergistically induced the expressions of AvBD9,AvBD10,and MUC2 in chicken HD11 cells(P<0.05)and the synergy was maintained in the presence of LPS.Butyrate and forskolin also suppressed LPS-induced IL-1βgene expression in HD11 cells in a synergistic manner(P<0.05).The two compounds significantly reduced the intestinal lesions of C.perfringens-challenged chickens when combined(P<0.05),but not individually.Furthermore,butyrate in combination with forskolin-containing CF extract had no influence on weight gain,but significantly reduced feed intake(P<0.05)with a strong tendency to improve feed efficiency(P=0.07)in a 42-d feeding trial.Desirably,the butyrate/forskolin combination significantly decreased abdominal fat deposition(P=0.01)with no impact on the carcass yield,breast meat color,drip loss,or pH of d-42 broilers.Conclusions:Butyrate and forskolin has potential to be developed as novel antibiotic alternatives to improve disease resistance,feed efficiency,and carcass composition of broilers.
基金provided by the precise assessment of the combined toxic effects of major mycotoxins on monogastric animals(2023YFD1301002).
文摘Background Necrotic enteritis(NE)can cause intestinal barrier dysfunction in broilers,leading to secondary liver injury(SLI).In this process,the gut-liver axis plays a crucial role.Lonicerae flos and turmeric extracts(LTE),containing chlorogenic acid and curcumin,have been reported to possess anti-inflammatory,and antioxidant properties.Based on these potential biological benefits,this study aims to investigate the reparative effects of LTE on the intestinal barrier dysfunction in NE-infected broilers and assess its therapeutic efficacy in alleviating SLI.By elucidating the regulatory mechanisms of LTE on gut-liver axis health,this research provides new insights into the prevention and treatment of NE in broilers.Results LTE improved body weight and average daily gain while reducing intestinal lesion scores,coccidia oocysts,and Clostridium perfringens counts in NE broilers(P<0.05).LTE enhanced intestinal morphology and up-regulated the expression of tight junction protein genes(CLDN1,TJP1)and MUC2,suppressed pro-inflammatory cytokine and myeloperoxidase(MPO)levels,and minimized endotoxin(ET)accumulation in NE broilers(P<0.05).Furthermore,LTE alleviated oxidative stress in ileal cells and protected mitochondrial structure and function in NE broilers.NE infection induced intestinal permeability in broilers,leading to increased serum pro-inflammatory cytokines and intestinal-derived endotoxin levels,which caused liver damage.LTE significantly reduced liver pathologic damage,pro-inflammatory cytokine levels,aspartate transaminase,alanine aminotransferase,and ROS levels in NE broilers(P<0.05).Additionally,16S rRNA sequencing revealed that NE significantly increased the relative abundance of Barnesiella and decreased the relative abundance of Bacteroidota,Desulfobacterota and Bacteroides in the cecum of broilers.LTE enhanced intestinal microbiota diversity and reduced the segregation of intestinal microbiota induced by NE infection.Conclusions In summary,LTE can alleviate NE and SLI by modulating the microbiota,inhibiting inflammation and oxidative stress,and ameliorating mitochondrial dysfunction,thereby enhancing gut-liver axis health and growth performance.
文摘Cytomegalovirus(CMV)infection of the gastrointestinal (GI)tract has been reported in both immunocompetent and,more frequently,in immunocompromised patients.We describe a case of a 19-year-old male who developed CMV infection of the terminal ileum while receiving immunosuppression for lupus nephritis. This was a distinctly unusual site of infection which clinically mimicked Crohn's ileitis.We note that reports of terminal ileal CMV infection have been infrequent. Despite a complicated hospital course,ganciclovir therapy was effective in resolving his symptoms and normalizing his ileal mucosa.This report highlights the importance of accurate histological diagnosis and clinical follow-up of lupus patients with GI symptoms undergoing intense immunosuppression.
文摘BACKGROUND With programmed death-1(PD-1) inhibitors becoming the standard treatment for lung cancer,PD-1-related adverse reactions and treatment have gradually become prominent.CASE SUMMARY First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles.The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms,abdominal computed tomography and colonoscopy improved,significant diarrhea was not occurred.CONCLUSION Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.
基金supported by the National Natural Science Foundation of China(32272910)the Shandong Provincial Postdoctoral Program for Innovative Talent(SDBX2021013)the Shandong Province Agricultural Industry Technology(SDAIT-11-08)。
文摘Background The poultry industry needs effective antibiotic alternatives to control outbreaks of necrotic enteritis(NE)caused by Clostridium perfringens.Methods The aim of this study was to investigate the effects of dietary supplementation with Macleaya cordata extract(MCE)on the immune function and gut microbiota of broilers with NE.A total of 2881-day-old broiler chicks were randomly assigned to a 2×2 factorial arrangement with two concentrations of dietary MCE supplementation(0 or 350 mg/kg of diet)and two disease challenge statuses(control or NE).Results The results revealed that NE significantly increased the feed conversion rate(FCR),mortality,intestinal lesion score,the levels of IL-1β,IL-17 and IFN-γ/IL-4 in serum and IL-17/IL-10 in the jejunal mucosa,m RNA levels of TLR2,IFN-γand p Ig R in the jejunum,and Clostridium perfringens concentrations in the cecum.NE significantly decreased the body weight(BW),body weight gain(BWG),jejunal villus height,V/C,m RNA level of AMPK-α1 in jejunum,IL-4 level in the jejunal mucosa and lactic acid bacteria abundance in the cecum.MCE significantly increased BW,BWG,jejunal villus height,V/C,m RNA levels of occludin,ZO-1 and AMPK-α1 in the jejunum,the levels of Ig A and Ig G in serum and IL-10 in the jejunal mucosa and m RNA levels of NF-κB,IL-10 and MHC-II in the jejunum.Additionally,MCE significantly decreased the FCR,mortality,intestinal lesion score,jejunal crypt depth,the levels of IFN-γand IL-17 in serum and IL-17/IL-10 in the jejunal mucosa,Clostridium perfringens concentrations in the cecum,and m RNA levels of IL-17/IL-10 in the jejunum.Moreover,NE significantly increased the abundance of bacteria that are associated with inflammation,obesity and depression(Alistipes,Barnesiella,Intestinimonas,RF39 and UCG-005)and significantly decreased the abundance of short-chain fatty acid(SCFA)-producing bacteria(Anaerotruncus,Butyricicoccus and Bacteroides)in the cecum.MCE significantly increased the abundance of SCFA-producing bacteria(Streptococcus,Ruminococcus_torques_group and Lachnospiraceae_NK4A136_group)and significantly reduced the abundance of bacteria that are associated with inflammation and obesity(Alistipes,Barnesiella and UCG-010)in the cecum.In the cecum of broilers with NE,the relative abundance of Barnesiella and Alistipes was higher and that of Lachnoclostridium and Shuttleworthia was lower.Interestingly,these trends were reversed by the addition of MCE to the diet.Spearman correlation analysis showed that Barnesiella and Alistipes were associated with enhanced intestinal inflammation and inhibited growth performance,whereas Lachnoclostridium and Shuttleworthia were associated with anti-inflammatory effects.Conclusions MCE ameliorated the loss of growth performance in broiler chickens with NE,probably by regulating the intestinal barrier,immune function,and gut microbiota.
基金supported by the National Natural Science Foundation of China(No.81700471 and No.82270583)the National Key Research and Development Program of China(No.2022YFC2504005)。
文摘Objective:Diabetes-induced gastrointestinal(GI)motility disorders are increasingly prevalent.Damage to the enteric nervous system(ENS),composed primarily of enteric neurons and glial cells,is an essential mechanism involved in these disorders.Although electroacupuncture(EA)has shown the potential to mitigate enteric neuronal loss,its mechanism is not fully understood.Additionally,the effects of EA on enteric glial cells have not been investigated.Enteric neural precursor cells(ENPCs)contribute to the structural and functional integrity of the ENS,yet whether EA enhances their differentiation into enteric neurons and glial cells remains unexplored.This study investigates whether EA promotes ENS repair through enhancing ENPC-derived neurogenesis and gliogenesis and elucidates the potential molecular mechanisms involved.Methods:Transgenic mice were used to trace Nestin+/nerve growth factor receptor(Ngfr)+ENPCs labeled with green fluorescent protein(GFP)in vivo.Mice were randomly divided into four groups:control,diabetes mellitus(DM),DM+sham EA,and DM+EA.The effects of EA on diabetic mice were evaluated by GI motility,ENS structure,and ENPC differentiation.Glial cell line-derived neurotrophic factor(GDNF)/Ret signaling was detected to clarify the underlying molecular mechanisms.Results:EA alleviated diabetes-induced GI motility disorders,as indicated by reduced whole gut transit time,shortened colonic bead expulsion time,and enhanced smooth muscle contractility.Furthermore,EA attenuated diabetes-induced losses of enteric neurons and glial cells,thereby restoring ENS integrity.Notably,EA reversed the diabetes-induced decrease in ENPCs and significantly increased the absolute number and the proportion of ENPC-derived enteric neurons.However,immunofluorescence analyses revealed no colocalization between EA-induced glial fibrillary acidic protein+glial cells and GFPlabeled ENPCs.Mechanistically,GDNF/Ret signaling was elevated in intestinal tissues and upregulated in ENPCs in EA-treated diabetic mice.Conclusion:EA facilitates ENS repair by promoting Nestin+/Ngfr+ENPC differentiation into enteric neurons via upregulation of GDNF/Ret signaling,and driving enteric gliogenesis from non-Nestin+/Ngfr+ENPCs.These findings highlight EA's role in ameliorating diabetes-induced GI dysmotility through ENPC-derived ENS restoration.
基金supported by National Natural Science Foundation of China(32170102)Natural Science Foundation of Tianjin(25JCLMJC00400)the Fundamental Research Funds for the Central Universities(63253191).
文摘Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis,but its colonizing and therapeutic efficacy after oral administration are limited.Here,we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein(MMPB)with the famous probiotic bacteria Lactobacillus plantarum(Lac)and Bifidobacterium animalis subsp.lactis(Bif).The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein.Owing to presence of the artificial protein on the MMPB surface,the nanodrug strongly bound and cross-linked the probiotic cells,forming the Lac+Bif+MMPB co-assembly.During co-incubation with the kanamycin-resistant E.coli strain(Ecka),the co-assembly strongly reduced the viability of Ecka,leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2.After oral administration of the co-assembly to themice pre-colonized by Ecka,Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine,and led to 2-3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif.More importantly,in the mice suffering from enteritis caused by drug-resistant S.Tm,the co-assembly remarkably recovered the mouse body weight,reduced intestine colonization of S.Tm cells,and decreased the levels of pro-inflammatory cytokines in both serum and colons.This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.
基金The China Agriculture Research System Program(Project No.CARS-41-G04)Shenyang Governmental Science and Technology Program(Project No.22316-2-02)supported this work.
文摘Background Clostridium perfringens is a pathogen that secretes multiple toxins,impacting humans and animals.It can cause intestinal diseases such as necrotic enteritis.Although tannins inhibit C.perfringens proliferation,the precise underlying mechanisms are unclear.Objective This study integrated transcriptomics and metabolomics to systematically investigate the mechanism by which tannins,specifically pentagalloylglucose(PGG)and tannic acid(TA),inhibit C.perfringens and potential pathways to alleviate infection in vivo.Results Ion concentration measurements,flow cytometric analysis,and transmission electron microscopy revealed that PGG and TA damaged the cell membrane structure of C.perfringens,triggering cytoplasmic content leakage.Additionally,PGG and TA significantly affected C.perfringens at the transcriptional and metabolic levels.Bioinformatics analysis revealed that PGG and TA induced amino acid restriction,disrupted energy metabolism,and impeded the ability of C.perfringens to sense and respond to the external environment.In an in vitro C.perfringens-infected intestinal cell model,PGG and TA boundαtoxin,significantly reduced the mRNA expression of inflammatory factors,and improved intestinal barrier function and cell viability.Compared to PGG,TA exhibited stronger inhibitory activity against C.perfringens and binding toαtoxin.In vivo,PGG and TA alleviated C.perfringens-induced weight loss in mice,improved intestinal villi morphology,and reduced intestinal inflammation and tight junction gene dysregulation.Conclusion These findings indicate that tannins inhibit C.perfringens,improve gut tissue integrity and reduce inflammation,demonstrating their multi-target effects of resisting intestinal diseases caused by harmful bacteria.This offers new insights for plant polyphenol-based strategies against necrotic enteritis.
基金Four“batches”innovation project of invigorating medicine through science and technology of Shanxi province(Project No.:2023XM059)。
文摘Objective:To investigate the clinical efficacy of Modified Gegen Qinlian Decoction combined with probiotics(Clostridium butyricum live capsules)in treating radiation enteritis(RE)in tumor patients,as well as its regulatory effect on the structure of intestinal flora,providing clinical evidence for the integrated traditional Chinese and Western medicine treatment of radiation enteritis.Methods:A total of 40 patients with radiation enteritis admitted to the Oncology Department of Linfen Central Hospital from September 2023 to December 2024 were selected and divided into an observation group and a control group according to the random number table method,with 20 cases in each group.The control group was treated with Clostridium butyricum live capsules,while the observation group was treated with Modified Gegen Qinlian Decoction in addition to the treatment given to the control group.Both groups received a 4-week treatment course.Intestinal function indicators and changes in intestinal flora structure were compared between the two groups before and after treatment,and clinical efficacy was evaluated.Results:After 4 weeks of treatment,the total effective rate in the observation group versus the control group was(95.00%vs 65.00%),with a statistically significant difference(P<0.05).The fecal formation rate in the observation group(85.00%vs 60.00%)was significantly higher than that in the control group,and the defecation frequency(2.15±0.42 vs 3.85±0.65)times/day was significantly lower than that in the control group,with statistically significant differences(P<0.05).After treatment,the quantities of Bifidobacterium(6.85±0.72 L vs 5.23±0.61 L)gCFU/g and Lactobacillus(6.52±0.68 L vs 4.98±0.57 L)gCFU/g in the observation group were significantly higher than those in the control group,while the quantities of Escherichia coli(4.12±0.53 L vs 5.67±0.65 L)gCFU/g and Staphylococcus(3.85±0.48 L vs 5.23±0.59 L)gCFU/g were significantly lower than those in the control group,with statistically significant differences(P<0.05).Conclusion:Clinical studies have confirmed that the synergistic treatment of radiation enteritis with Modified Gegen Qinlian Decoction and probiotics can significantly improve patients’clinical symptoms and restore the balance of intestinal flora,providing an effective regimen for clinical treatment.
基金Supported by People's Livelihood Science and Technology Plan Joint Project of Liaoning Province,No.2021JH2/10300083。
文摘BACKGROUND Radiation enteritis is a common complication of radiation therapy in which the surrounding normal intestinal tissue is damaged by ionising radiation,and there is no standard pharmacological prophylaxis or treatment regimen available.Mesenchymal stem cell transplantation can be used for radiation protection and the treatment of acute radiation injury,but its therapeutic mechanism of action remains unclear.AIM To investigate the protective effects of autologous bone marrow-derived mesenchymal stem cell(ABMSC)transplantation on radiation-induced intestinal injury.METHODS A model of acute radioactive enteritis was established in dogs by applying abdominal intensity-modulated radiation at a single X-ray dose of 12 Gy.ABMSCs were transplanted into the mesenteric artery with the technology of femoral artery puncture and DSA imaging two days after radiation.Visual and histopathological changes of the experimental dogs were observed.Different kinds of cytokines from intestinal samples were tested using Quantibody Canine Cytokine Array method.Enzyme-linked immunosorbent assay(ELISA)was also used to evaluate the cytokines changes in serum.RESULTS The ABMSCs group showed significant improvements in survival status compared with the blank and saline treatment groups.Histological observations revealed that the former had lower histological scores than the later after treatment(P<0.05).Compared to the control groups,interleukin(IL)-10 and monocyte chemotactic protein(MCP)-1 from intestinal samples showed a remarkable increase and ELISA of serum samples proved higher secretion of the two target cytokines in the ABMSCs group(P<0.05).CONCLUSION Our data suggest that transplantation of ABMSCs promotes intestinal recovery after acute radioactive injury in Beagle dogs.The cytokines of IL-10 and MCP-1 might play an important role in this process.
文摘Objective:To evaluate the clinical efficacy of cefixime(Cef)combined with montmorillonite powder(MP)in treating pediatric bacterial enteritis.Methods:Seventy-two cases of bacterial enteritis in children admitted between October 2021 and October 2023 were selected and randomly divided into two groups.The combination group received Cef treatment alongside MP,while the control group received only Cef treatment.The groups were compared based on overall efficacy,symptom relief time,and other indicators.Results:The combination group showed a higher overall efficacy,shorter symptom relief time,lower levels of inflammatory markers post-treatment,and a higher proportion of normal and grade I dysbiosis in the intestinal flora,with significant differences compared to the control group(P<0.05).Conclusion:Cef combined with MP is significantly effective in treating pediatric bacterial enteritis,promoting symptom relief,reducing inflammation,and correcting intestinal flora imbalance.
基金AB Vista(Marlborough,Wiltshire,UK)for providing the feed additives and funding this research。
文摘Background:Two experiments were conducted to establish an optimal NE challenge model and evaluate the efficacy of stimbiotic(STB)supplementation in necrotic enteritis(NE)challenged broilers.In Exp.1,a total of 120 Arbor Acres(AA)broilers(45.0±0.21 g)were randomly assigned to 6 treatments in a 3×2 factorial arrangement.Vaccine treatments included non-challenge(0),×10 the recommended dose(×10)or×20 the recommended dose(×20)by the manufacturer.Clostridium perfringens(CP)treatments were non-challenge(No)or 3 mL of 2.2×10^(7)CFU CP challenge(Yes).In Exp.2,a total of 72 AA broilers(40.17±0.27 g)were randomly assigned to 6 treatments in a 3×2 factorial arrangement.Dietary treatments included non-additive(CON),100 mg/kg STB(STB)and 100 mg/kg STB on top of a typical commercial blend including an essential oil,probiotics,and enzyme(CB).Challenge treatments included non-NE challenge(No)and NE challenge(Yes)as established in Exp.1.Results:In Exp.1,CP and vaccine challenge decreased(P<0.05)body weight(BW),body weight gain(BWG)and feed intake(FI),and increased(P<0.05)the number of broilers with diarrhea and intestinal lesions.The oral administration of×20 recommended dose of vaccines coupled with 3 mL of 2.2×10^(7)CFU CP resulted in(P<0.01)a significantly increased incidence of wet litter and intestinal lesions.Thus,this treatment was chosen as the challenge model for the successful inducement of NE in Exp.2.In Exp.2,the NE challenge negatively affected(P<0.01)growth performance,ileal morphology,immunoglobulin contents in blood,caecal microbiota in the caecum,footpad dermatitis,intestinal lesion scores,tumour necrosis factor(TNF-α)and endotoxin in the serum compared with the non-NE challenged birds.The supplementation of STB and CB in diets enhanced(P<0.05)growth performance,intestinal microbiota,and blood profiles by stimulating ileal morphology(VH and VH:CD)and propionate production in the cecum,and there were no differences in measured variables between STB and CB supplemented birds.Conclusion:Overall,these results indicate that STB supplementation was able to reduce the inflammatory response and improve the performance of NE challenged birds,and the supplementation of STB alone was as effective as a typical commercial blend containing a number of other additives.
文摘Objective:To explore the effectiveness of early enteral nutrition therapy in ICU patients with respiratory failure.Methods:A total of 76 ICU patients with respiratory failure,admitted from May 2024 to May 2025,were included in the study.They were divided into an observation group and a control group using a random number table method,and relevant treatment indicators were compared.Results:The total effective rate in the observation group was higher than that in the control group(p<0.05).After treatment,the observation group showed superior lung function,organ function,health status,nutritional status,body mass index,and blood gas analysis indicators compared to the control group(p<0.05).Conclusion:Early enteral nutrition therapy is effective in treating ICU patients with respiratory failure and is beneficial for improving their lung function,nutritional status,and blood gas parameters,making it worthy of promotion.
