Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mecha...Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.展开更多
The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a se...The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compo...Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.展开更多
Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.展开更多
Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates...Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.展开更多
Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a n...Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.展开更多
A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-caten...A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.展开更多
Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated ...Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
BACKGROUND Endoscopic mucosa resection(EMR)is an important minimally invasive surgical method for treating early digestive tract tumors.In recent years,the crucial role of intestinal microbiota in disease occurrence a...BACKGROUND Endoscopic mucosa resection(EMR)is an important minimally invasive surgical method for treating early digestive tract tumors.In recent years,the crucial role of intestinal microbiota in disease occurrence and development has attracted increasing attention.However,the changes in intestinal microbiota after EMR and the effect of dietary fiber intervention on microbiota recovery remain insufficiently elucidated.AIM To investigate the effects of dietary fiber intervention on intestinal microbiota recovery in patients undergoing EMR and evaluate its potential to improve postoperative outcomes and intestinal microecological balance.METHODS This retrospective study analyzed intestinal microbiota sequencing and dietary fiber intervention in patients with EMR.Patients who underwent EMR surgery between 2020 and 2023 were selected and divided into a routine follow-up group and a dietary fiber intervention group.High-throughput 16S rRNA gene sequencing was performed to detect changes in patient intestinal microbiota,and microbiota diversity,structure,and function in different intervention groups were compared and analyzed.RESULTS A total of 86 patients with EMR were included in the study.Results showed that:(1)Intestinal microbiota diversity significantly decreased after EMR surgery,with notable changes in the proportion of Gram-negative bacilli and anaerobic bacteria;(2)The microbiota recovery rate in the dietary fiber intervention group was significantly higher than that in the control group,with a significantly higher microbiota diversity index(P<0.05);and(3)The abundance of lactobacilli and bifidobacteria in the intervention group increased substantially,and intestinal barrier-related functional gene expression was upregulated.CONCLUSION Dietary fiber intervention can effectively promote intestinal microbiota recovery in patients with EMR,improve intestinal microecological balance,and provide a new intervention strategy for clinical post-EMR patient rehabilitation.展开更多
Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Background This study investigated the effects of different non-starch polysaccharide(NSP)sources with NSP degrading enzymes(NSPases)and the influence on the mucosa-associated microbiota and intestinal immunity of nur...Background This study investigated the effects of different non-starch polysaccharide(NSP)sources with NSP degrading enzymes(NSPases)and the influence on the mucosa-associated microbiota and intestinal immunity of nursery pigs,on growth performance and carcass traits at market weight.Methods One hundred and sixty newly weaned pigs at 7.0±0.3 kg body weight(BW)were allotted in a 2×2 factorial with NSP sources and NSPases serving as factors.The 4 dietary treatments were:DDGS,corn distillers'dried grains with solubles as source of NSP;DDGS+NSPases(DDGS+),DDGS with xylanase at 0.01%,3,000 U/kg of feed andβ-mannanase at 0.05%,400 U/kg of feed;SHWB,soybean hulls and wheat bran replacing corn DDGS as the source of NSP;SHWB with NSPases(SHWB+),SHWB with xylanase at 0.01%,3,000 U/kg of feed andβ-mannanase at 0.05%,400 U/kg of feed.Pigs were fed for 37 d and housed in groups of 4 pigs per pen.At d 37,the median body weight pig in each pen was euthanized for sampling to analyze intestinal health parameters.Remaining pigs were fed a common diet for subsequent phases to evaluate the carryover effect on growth and carcass traits.Results The SHWB decreased(P<0.05)the relative abundance of Helicobacter,tended to increase(P=0.074)the relative abundance of Lactobacillus,increased(P<0.05)immunoglobulin G(IgG)in the jejunal mucosa,tended to increase(P=0.096)the villus height(VH)in the jejunum,and tended to improve ADG(P=0.099)and feed efficiency(P=0.068)during phase 1 compared to DDGS treatment.Supplementation of NSPases increased(P<0.05)Shannon index of diversity,increased the relative abundance of Streptococcus and Acinetobacter,and tended to increase(P=0.082)dry matter digestibility.The BW of pigs fed SHWB was more uniform(P<0.05)at the end of the 120 d study.Additionally,hot carcass weight of pigs fed SHWB tended to be more uniform(P=0.089)than DDGS treatment.Conclusion Soybean hulls and wheat bran replacing DDGS in nursery diets improved uniformity of pigs at market weight,which might be attributed to beneficial modulation of the mucosa-associated microbiota and enhanced intestinal morphology during the nursery phase.Supplementation of NSPases had beneficial effects on the intestinal mucosa-associated microbiota,digestibility,and intestinal immunity in SHWB treatment,whereas no carryover effects were overserved at market weight.展开更多
Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut mic...Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut microbiota,bile acids(BAs)play a protective role in maintaining gut homeostasis.However,the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored.Therefore,the aim of this study was to investigate the potential role of feeding BAs in protecting against S.Typhimurium infection in broilers.Methods A total of 1441-day-old Arbor Acres male broilers were randomly assigned to 4 groups,including non-challenged birds fed a basal diet(CON),S.Typhimurium-challenged birds(ST),S.Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection(ST-ANT),and S.Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs(ST-BA).Results BAs supplementation ameliorated weight loss induced by S.Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers(P<0.05).Compared to the ST group,broilers in ST-BA group had a higher ileal mucosal thickness and villus height,and BAs also ameliorated the increase of diamine oxidase(DAO)level in serum(P<0.05).It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells(GCs)were increased in the ST-BA group,consistent with the upregulation of MUC2 gene expression in the ileal mucosa(P<0.05).Moreover,the m RNA expressions of Toll-like receptor 5(TLR5),Toll-like receptor 4(TLR4),and interleukin 1 beta(IL1b)were downregulated in the ileum by BAs treatment(P<0.05).16S rDNA sequencing analysis revealed that,compared to ST group,BAs ameliorated the decreases in Bacteroidota,Bacteroidaceae and Bacteroides abundances,which were negatively correlated with serum DAO activity,and the increases in Campylobacterota,Campylobacteraceae and Campylobacter abundances,which were negatively correlated with body weight but positively correlated with serum D-lactic acid(D-LA)levels(P<0.05).Conclusions Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota,which eventually relieves the damage to the intestinal barrier and weight loss induced by S.Typhimurium infection in broilers.展开更多
The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and ...The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.展开更多
In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intes...In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intestinal wall thickness of duodenum, jejunum and ileum of 42-day-old broilers, so as to study the effects of different conncentrations of homologous probiottcs on small intestinal mucosa struc- ture of the broilers. The results showed that the effect of 0.3% probiotics on small intestine mucosal structures was the best, such as the length of intestinal villus was the longest, the ratio of villus length to crypt depth was the largest, the thins of mucous membrane and intestinal wall was the thickest. These showed that 0,3% probiotics had best effect on improving and enhancing the digestion-absorption func- tion of the small intestine of the broilers.展开更多
Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotox...Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.展开更多
AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly dist...AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.展开更多
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
基金financially supported by the Project of National Key R&D Program of China(2022YFD1300403)the Natural Science Foundation of Hubei Province Project(2024AFB926)Hubei Provincial Science and Technology Program(2025CSA037)。
文摘Backgrounds Deoxynivalenol(DON)is an abundant environmental pollutant in feed,posing serious health hazards to animals.However,whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood.Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.Methods Firstly,two groups of weaning pigs were fed a basal diet,or basal diet supplemented with 4 mg DON/kg for 3 weeks.Additionally,another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline.In addition,the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line(IPEC-1)by overexpressed plasmids of dynamin related protein 1(Drp1)and mitofusin 2(Mfn2)which were determined by animal studies.Finally,a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.Results Dietary DON caused jejunal damage and inflammation,reduced intestinal Drp1,mitofusin 1(Mfn1)and Mfn2,and induced cell apoptosis.DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2,and increased cell apoptosis.Moreover,DON challenge also resulted in cell damage and mitochondrial dysfunction,accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells.Subsequently,Mfn2,but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression,suppressed cell apoptosis,mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge.Finally,M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis,rescued mitochondrial dysfunction,barrier function impairment and cell damage.Conclusions Overall,our study demonstrates that DON exposure triggers Mfn2 protein dysregulation,which in turn mediates DON-induced intestinal epithelial damage in piglets.
基金Financial support from the National Natural Science Foundation of China(32502106)One health Interdisciplinary Research Project,Institute of One Health Science,Ningbo University(NBUOH202502)the Ningbo Top Talent Project(215-432094250).
文摘The antioxidant activity of selenium-containing soybean peptides(SePPs)has been previously demonstrated,despite their limited absorption in the small intestine.This study investigates the antioxidant mechanism of a selenium-containing tetrapeptide,Ser-Phe-Gln-SeM(SFQSeM),identified from SePPs,with particular emphasis on its interaction with the intestinal microbiota and its role in modulating host antioxidant defenses.The effects of SFQSeM were evaluated in a D-galactose-induced oxidative stress model and an antibiotictreated mouse model.SFQSeM supplementation significantly reduced the oxidative stress in D-galactosetreated mice.It also promoted the growth of beneficial bacteria and increased the levels of acetate,butyrate and lactate in the intestine(P<0.05).In the antibiotic-treated mouse model,depletion of the intestinal microbiota significantly reduced hepatic glutathione peroxidase(GSH-Px)activity(26.6%)and glutathione peroxidase 1(GPx-1)expression(48.77%)compared to normal mice supplemented with SFQSeM(P<0.05).In contrast to Na_(2)SeO_(3)and selenomethionine,SFQSeM effectively restored the diversity of the intestinal microbiota disrupted by antibiotics.Lactobacillus,Lachnospiraceae_NK4A136_group,and Muribaculaceae were identified as predominant bacteria in the SFQSeM group,and were strongly associated with increased hepatic GSH-Px activity and GPx-1 mRNA expression(P<0.05).In conclusion,intestinal microbiota enhances the antioxidant efficacy of SFQSeM by modulating microbial composition,producing active metabolites,and converting SFQSeM into a bioactive form of selenium.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
基金funded by the National Natural Science Foundation of China(32101915)Natural Science Foundation of Jiangxi Province(20224BAB205005)+1 种基金Training Program for Academic and Technical Leaders of Major Disciplines in Jiangxi Province(20232BCJ23090)Natural Science Foundation of Chongqing(CSTB2023NSCQMSX0497).
文摘Limosilactobacillus reuteri is a vertebrate symbiont that is widely appreciated as being of significant ecological importance for human health.As a unique feature,L.reuteri converts glycerol to the antimicrobial compound reuterin using enzymes encoded in its propanediol-utilization operon and evolves with host-driven diversification.Reuterin-producing L.reuteri HLRE13 was selectively isolated from poultry previously and confirmed to inhibit the growth of Staphylococcus aureus in vitro.However,it remains unclear whether L.reuteri HLRE13 retains these antagonistic properties when ingested in specific-pathogen-free mice.Here,we investigated the ameliorative effects and potential mechanisms of action of L.reuteri HLRE13 in combination with glycerol on S.aureus-induced infection phenotypes in mice.Firstly,our results confirmed that L.reuteri HLRE13 effectively inhibited the intestinal colonization of S.aureus CMCC26003;Secondly,L.reuteri HLRE13 combined with glycerol could alleviate the intestinal tissues damage caused by S.aureus through increasing the expression of ZO-1,Occludin,and MUC-2,ameliorate the intestinal systemic inflammatory response,and maintain the balance of gut microbiota by increasing the relative abundance of Lactobacillus and reducing the relative abundance of Staphylococcus.Furthermore,the colonization resistance was also found on L.reuteri HLRE13 combined with glycerol against S.aureus in pseudo germ-free mice,and they exerted the similar effects on alleviating intestinal damage and improving immune function.Combining these results,we speculate that reuterin-producing L.reuteri antagonize S.aureus in mice without the gut microbiota-dependent manner.Overall,our findings will provide a theoretical foundation for the scientific cognition of L.reiteri in maintaining intestinal health by producing reuterin.
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
基金funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
文摘Background Inflammatory bowel disease causes intestinal structural damage,impairs gut function,hinders animal growth and development,and reduces farming efficiency.Previous studies demonstrated that lactate alleviates dextran sulfate sodium(DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions.However,the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear.This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.Methods A total of 6021-day-old weaned female piglets were randomly assigned into three groups based on weight:the control group(basal diet with physiological saline gavage),the DSS group(basal diet with 5%DSS gavage),and the DSS+LA group(2%lactate diet with 5%DSS gavage).There were 10 replicates per treatment,with 2 piglets per replicate.Jejunal morphology was assessed via hematoxylin and eosin staining,while Western blotting quantified the protein levels of proliferation markers,including cluster of differentiation 24(CD24),cyclin D1,and wingless/integrated(Wnt)/β-catenin signaling components.In vitro,0.08%DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2(IPEC-J2)cells(n=4)were assessed for viability(Cell Counting Kit-8 assay),apoptosis(flow cytometry),and proliferation parameters,including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5+)stem cell quantification.Results In vivo,DSS administration induced jejunal villus shortening(P<0.05),downregulated protein levels of CD24,cyclin D1,casein kinase 1(CK1),and dishevelled-2(DVL2)(P<0.05).In vitro,DSS promoted apoptosis,inhibited proliferation,diminished the Lgr5+cell populations(P<0.05),and reduced S-phase cell proportions(P<0.05).Conversely,lactate supplementation ameliorated DSS-induced villus atrophy(P<0.05),restored CD24,cyclin D1,CK1,and DVL2 protein levels(P<0.05).Furthermore,in vitro,sodium lactate attenuated DSS-induced apoptosis(P<0.05),enhanced IPEC-J2 proliferation(P<0.05),expanded Lgr5+cells(P<0.05),and increased S-phase progression(P<0.05).Conclusions In summary,lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis.This study provides novel mechanistic evidence supporting lactate's therapeutic potential for IBD management.
基金funded by Beijing Natural Science Foundation(6252001)Guangdong Basic and Applied Basic Research Foundation(2022A1515140021)Natural Science Foundation of China(31871772).
文摘Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.
文摘A recent preclinical study reported that Wumei Pills(WMP)and Lactobacillus reuteri(L.reuteri)mitigate 5-fluorouracil-induced intestinal mucositis by promoting intestinal stem cell(ISC)-mediated repair via Wnt/β-catenin signaling.The mechanistic interpretation rests largely on systemic inflammation readouts,correlative microbiota changes,and immunohistochemistry of pathway markers.From a clinical standpoint,chemotherapy-induced mucositis remains a common and burdensome toxicity that leads to dose reductions,treatment delays,and infection risk;current care is largely supportive and does not directly restore ISCmediated repair.This unmet need motivates rigorous appraisal of the proposed“WMP→L.reuteri→ISC/Wnt”axis.To highlight key methodological considerations that may affect causal inference and analytical rigor in the proposed“WMP→L.reuteri→ISC/Wnt”pathway.This letter critically appraises the study’s design,endpoints,and analyses against current best practices in mucositis biology,microbiome causality testing,Wnt/β-catenin pathway validation,and preclinical statistics,and synthesizes concrete,literature-grounded remedies.Six issues with potential impact on interpretation were identified:(1)Reliance on serum cytokines/lipopolysaccharide to infer local mucosal inflammation,with limited tissue-level indices(e.g.,myeloperoxidase,interleukin-1β,immune-cell infiltration);(2)Absence of necessity/sufficiency tests to verify microbiota mediation(e.g.,L.reuteri depletion,WMP-donor fecal microbiota transplantation,probiotic add-back);(3)Pathway evidence tiering-Wnt/β-catenin activation not confirmed byβ-catenin nuclear translocation or downstream targets(Axin2,c-Myc,cyclin D1),and Lgr5 quantification/specificity insufficient;(4)Statistical design under-specified(power justification,blinded assessment,control of multiple comparisons)and potential cage effects unmodeled;(5)Limited dose-response and safety profiling for WMP/L.reuteri;and(6)Constrained generalizability(single sex/strain/age,lack of ABX-only controls,single time-point).The reported benefits of WMP and L.reuteri in chemotherapy-induced mucositis are promising,but stronger causal and analytical foundations are needed.Incorporating tissue-level inflammation readouts,microbiota loss-/gain-offunction designs,definitive Wnt/β-catenin activation assays,rigorous statistical practices(including mixed-effects models for cage clustering and multiplicity control),dose-response/safety evaluation,and broader experimental scope(sex/age/strain,ABX-only controls,time-course)will yield more robust and translationally relevant conclusions.
基金Supported by National High-Level Hospital Clinical Research Funding,No.2022-PUMCH-B-022,and No.2022-PUMCH-D-002CAMS Innovation Fund for Medical Sciences,No.CIFMS 2021-1-I2M-003Undergraduate Innovation Program,No.2024dcxm025.
文摘Small intestinal villi are essential for nutrient absorption,and their impairment can lead to malabsorption.Small intestinal villous atrophy(VA)encompasses a heterogeneous group of disorders,including immune-mediated conditions(e.g.,celiac disease,autoimmune enteropathy,inborn errors of immunity),lymphoproliferative disorders(e.g.,enteropathy-associated T-cell lymphoma),infectious causes(e.g.,tropical sprue,Whipple’s disease),iatrogenic factors(e.g.,Olmesartanassociated enteropathy,graft-vs-host disease),as well as inflammatory and idiopathic types.These disorders are often rare and challenging to distinguish due to overlapping clinical,serological,endoscopic,and histopathological features.Through a systematic literature search using keywords such as small intestinal VA,malabsorption,and specific enteropathies,this review provides a comprehensive overview of diagnostic clues for VA and malabsorption.We systematically summarize the pathological characteristics of each condition to assist pathologists and clinicians in accurately identifying the underlying etiologies.Current studies still have many limitations and lack broader and deeper investigations into these diseases.Therefore,future research should focus on the development of novel diagnostic tools,predictive models,therapeutic targets,and mechanistic molecular studies to refine both diagnosis and management strategies.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
文摘BACKGROUND Endoscopic mucosa resection(EMR)is an important minimally invasive surgical method for treating early digestive tract tumors.In recent years,the crucial role of intestinal microbiota in disease occurrence and development has attracted increasing attention.However,the changes in intestinal microbiota after EMR and the effect of dietary fiber intervention on microbiota recovery remain insufficiently elucidated.AIM To investigate the effects of dietary fiber intervention on intestinal microbiota recovery in patients undergoing EMR and evaluate its potential to improve postoperative outcomes and intestinal microecological balance.METHODS This retrospective study analyzed intestinal microbiota sequencing and dietary fiber intervention in patients with EMR.Patients who underwent EMR surgery between 2020 and 2023 were selected and divided into a routine follow-up group and a dietary fiber intervention group.High-throughput 16S rRNA gene sequencing was performed to detect changes in patient intestinal microbiota,and microbiota diversity,structure,and function in different intervention groups were compared and analyzed.RESULTS A total of 86 patients with EMR were included in the study.Results showed that:(1)Intestinal microbiota diversity significantly decreased after EMR surgery,with notable changes in the proportion of Gram-negative bacilli and anaerobic bacteria;(2)The microbiota recovery rate in the dietary fiber intervention group was significantly higher than that in the control group,with a significantly higher microbiota diversity index(P<0.05);and(3)The abundance of lactobacilli and bifidobacteria in the intervention group increased substantially,and intestinal barrier-related functional gene expression was upregulated.CONCLUSION Dietary fiber intervention can effectively promote intestinal microbiota recovery in patients with EMR,improve intestinal microecological balance,and provide a new intervention strategy for clinical post-EMR patient rehabilitation.
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金funded by North Carolina Agricultural Foundation(Raleigh,NC,USA)USDA-NIFA(Hatch#02893 and National Needs Fellowship#2019-38420-28970,Washington DC,USA)+1 种基金CJ Bio(Seoul,Korea)CTC Bio(Seoul,Korea)。
文摘Background This study investigated the effects of different non-starch polysaccharide(NSP)sources with NSP degrading enzymes(NSPases)and the influence on the mucosa-associated microbiota and intestinal immunity of nursery pigs,on growth performance and carcass traits at market weight.Methods One hundred and sixty newly weaned pigs at 7.0±0.3 kg body weight(BW)were allotted in a 2×2 factorial with NSP sources and NSPases serving as factors.The 4 dietary treatments were:DDGS,corn distillers'dried grains with solubles as source of NSP;DDGS+NSPases(DDGS+),DDGS with xylanase at 0.01%,3,000 U/kg of feed andβ-mannanase at 0.05%,400 U/kg of feed;SHWB,soybean hulls and wheat bran replacing corn DDGS as the source of NSP;SHWB with NSPases(SHWB+),SHWB with xylanase at 0.01%,3,000 U/kg of feed andβ-mannanase at 0.05%,400 U/kg of feed.Pigs were fed for 37 d and housed in groups of 4 pigs per pen.At d 37,the median body weight pig in each pen was euthanized for sampling to analyze intestinal health parameters.Remaining pigs were fed a common diet for subsequent phases to evaluate the carryover effect on growth and carcass traits.Results The SHWB decreased(P<0.05)the relative abundance of Helicobacter,tended to increase(P=0.074)the relative abundance of Lactobacillus,increased(P<0.05)immunoglobulin G(IgG)in the jejunal mucosa,tended to increase(P=0.096)the villus height(VH)in the jejunum,and tended to improve ADG(P=0.099)and feed efficiency(P=0.068)during phase 1 compared to DDGS treatment.Supplementation of NSPases increased(P<0.05)Shannon index of diversity,increased the relative abundance of Streptococcus and Acinetobacter,and tended to increase(P=0.082)dry matter digestibility.The BW of pigs fed SHWB was more uniform(P<0.05)at the end of the 120 d study.Additionally,hot carcass weight of pigs fed SHWB tended to be more uniform(P=0.089)than DDGS treatment.Conclusion Soybean hulls and wheat bran replacing DDGS in nursery diets improved uniformity of pigs at market weight,which might be attributed to beneficial modulation of the mucosa-associated microbiota and enhanced intestinal morphology during the nursery phase.Supplementation of NSPases had beneficial effects on the intestinal mucosa-associated microbiota,digestibility,and intestinal immunity in SHWB treatment,whereas no carryover effects were overserved at market weight.
基金The National Key R&D Program of China(2023YFD2000802)provided financial contributions。
文摘Background Salmonella Typhimurium(S.Typhimurium)is a common pathogenic microorganism and poses a threat to the efficiency of poultry farms.As signaling molecules regulating the interaction between the host and gut microbiota,bile acids(BAs)play a protective role in maintaining gut homeostasis.However,the antibacterial effect of BAs on Salmonella infection in broilers has remained unexplored.Therefore,the aim of this study was to investigate the potential role of feeding BAs in protecting against S.Typhimurium infection in broilers.Methods A total of 1441-day-old Arbor Acres male broilers were randomly assigned to 4 groups,including non-challenged birds fed a basal diet(CON),S.Typhimurium-challenged birds(ST),S.Typhimurium-challenged birds treated with 0.15 g/kg antibiotic after infection(ST-ANT),and S.Typhimurium-challenged birds fed a basal diet supplemented with 350 mg/kg of BAs(ST-BA).Results BAs supplementation ameliorated weight loss induced by S.Typhimurium infection and reduced the colonization of Salmonella in the liver and small intestine in broilers(P<0.05).Compared to the ST group,broilers in ST-BA group had a higher ileal mucosal thickness and villus height,and BAs also ameliorated the increase of diamine oxidase(DAO)level in serum(P<0.05).It was observed that the mucus layer thickness and the number of villous and cryptic goblet cells(GCs)were increased in the ST-BA group,consistent with the upregulation of MUC2 gene expression in the ileal mucosa(P<0.05).Moreover,the m RNA expressions of Toll-like receptor 5(TLR5),Toll-like receptor 4(TLR4),and interleukin 1 beta(IL1b)were downregulated in the ileum by BAs treatment(P<0.05).16S rDNA sequencing analysis revealed that,compared to ST group,BAs ameliorated the decreases in Bacteroidota,Bacteroidaceae and Bacteroides abundances,which were negatively correlated with serum DAO activity,and the increases in Campylobacterota,Campylobacteraceae and Campylobacter abundances,which were negatively correlated with body weight but positively correlated with serum D-lactic acid(D-LA)levels(P<0.05).Conclusions Dietary BAs supplementation strengthens the intestinal mucosal barrier and reverses dysbiosis of gut microbiota,which eventually relieves the damage to the intestinal barrier and weight loss induced by S.Typhimurium infection in broilers.
基金Liaoning Provincial Department of Education Project-General Project(LJKMZ20221060)National Key R&D Program of China(2022YFD1600505).
文摘The intestinal mucosa is the intestinal lumen tissue that protects the intestine from invasion,maintains intestinal barrier function,and participates in the immune response.Diseases such as inflammatory enteritis and intestinal infections can cause damage to the intestinal mucosal barrier and dysfunction.The aim of this study was to investigate the improvement mechanism of malvidin-3-O-galactoside(M3G)on small intestinal mucosal barrier function.C57BL/6J male mice were given dextran sodium sulfate(DSS)for 7 days to induce enteritis,and then were fed normally with or without M3G supplementation for another 7 days.The results showed that M3G supplementation significantly improved the disease activity index(DAI)score and small intestinal tissue injury in mice with DSS induced enteritis.M3G ameliorated the small intestinal mucosal mechanical barrier function by modulating the expression of mucin 2(MUC2),zona occludens 1(ZO-1),Occludin,Claudin-1,intestinal fatty acid binding protein(iFABP),and trefoil factor 3(TFF3)in the small intestine mucosa,and the serum levels of D-lactic acid(D-LA),lipopolysaccharide(LPS),and diamine oxidase(DAO)were significantly decreased.Additionally,M3G also relieved the small intestinal immunologic barrier of mice by decreasing the immune protein levels of immunoglobulin A(IgA),immunoglobulin M(IgM),and immunoglobulin G(IgG)in serum,and secretory immunoglobulin A(SIgA)level in small intestine tissue.Furthermore,M3G inhibited the expression of Notch pathway-related proteins such as Notch1,Notch intracellular domain(NICD),delta-like ligand 4(DLL4),delta-like ligand 1(DLL1),and hairy/enhancer of split 1(Hes1).In conclusion,the results demonstrated that M3G can improve intestinal mucosal barrier function by inhibiting Notch pathway.
基金Supported by the Project of Beijing Vocational College of Agriculture(XY-YF-14-18XYYF-14-16)~~
文摘In the study, the methods of applied histology and histochemistry were used to determine intestinal villus length, crypt depth, the ratio of intestinal villus length to crypt depth, mucous membrane thickness and intestinal wall thickness of duodenum, jejunum and ileum of 42-day-old broilers, so as to study the effects of different conncentrations of homologous probiottcs on small intestinal mucosa struc- ture of the broilers. The results showed that the effect of 0.3% probiotics on small intestine mucosal structures was the best, such as the length of intestinal villus was the longest, the ratio of villus length to crypt depth was the largest, the thins of mucous membrane and intestinal wall was the thickest. These showed that 0,3% probiotics had best effect on improving and enhancing the digestion-absorption func- tion of the small intestine of the broilers.
基金Project supported by the Traditional Chinese Medicine Science of Zhejiang Province (Nos. 2003C130 and 2004C142)the Medical Sci-ence and Technology of Zhejiang Province (No. 2003B134)the Technological Development of Hangzhou (No. 2003123B19), China
文摘Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.
基金Supported by Beijing Municipal Science & Technology Commission Major Scitech Program,No.H020920050130
文摘AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.
