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 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
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
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
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
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
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
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
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
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: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
Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing cli...Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.展开更多
Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites ...Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.Results In this study,we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score,and elevated levels of lipopolysaccharide(LPS)and D-lactate(D-LA)compared to healthy piglets.Subsequently,we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets.Diarrheal piglets demonstrated intestinal microbiota dysbiosis,characterized pri-marily by a higher Firmicutes to Bacteroidota ratio,a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri,and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron.Functional pro-filing of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes(KEGG)data was performed,and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diar-rhea.Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets.Furthermore,we explored the effects of dietary indole-3-aldehyde(IAld),a key tryptophan metabolite,on intestinal development and gut barrier function in weaned piglets.Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell(ISC)expansion in piglets.The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.Conclusions These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intesti-nal development by promoting ISC expansion in weaned piglets.展开更多
The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectiona...The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectional endoscopies. Insuspected mid-lower gastrointestinal bleeding (MLGIB) the diagnostic yield ofcolonoscopy is poor and may cause a delay in detecting small bowel disease. Acrucial aspect of small bowel capsule endoscope performance is the timing of theprocedure, the interval between the bleeding episode and capsule ingestion isinversely related to the diagnostic yield as confirmed by a recent meta-analysis.Currently the ongoing advances achieved by video CE in particular to evaluateboth small bowel and colon in a single test using double headed capsules, raisesquestions regarding the position of pan intestinal capsule in the current algorithmto investigate patients presenting with suspected MLGIB ahead of colonoscopy.Early evidence suggests pan intestinal capsule could fit well as a diagnostic“filter” test in this cohort of patients, thereby reserving invasive conventionalcolonoscopy or device assisted enteroscopy as therapeutics options only. The recentdevelopment of magnetically controlled CE and a blood sensing capsule pushthe boundaries of CE even further in patients presenting with suspected gastrointestinalbleeding. This review will discuss the current available evidence andfuture directions of CE in suspected MLGIB.展开更多
2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-...2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche ...BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.展开更多
BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are ra...BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.展开更多
BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recover...BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recovery of gastrointestinal function in children.AIM To compare and analyze the effects of different postoperative feeding methods on gastrointestinal function reconstruction in newborns with CIA.METHODS Twenty-six children diagnosed with neonatal CIA,treated with minimally invasive surgery at Shijiazhuang Maternal and Child Health Hospital between January 2021 and May 2024,were selected for this single-center prospective randomized controlled study.They were divided into two groups using envelope randomization:Enteral nutrition(EN)group(n=13)and parenteral nutrition(PN)group(n=13).Baseline and clinical characteristics were collected,and recovery time of bowel sounds and time to first defecation were used as evaluation indices for gastrointestinal functional reconstruction.Differences between the groups were analyzed using t-test,χ2 test,and Fisher’s exact test.Spearman’s correlation tests and linear regression models were employed to analyze factors influencing time to first defecation.RESULTS The time to bowel sound recovery(51.54 vs 65.85,P=0.013)and first defecation(58.15 vs 76.62,P<0.001)was shorter in the EN group compared to the PN group.Clinical improvements in the EN group,including discharge weight(P=0.044),hospital stay(P=0.027),white blood cell count(P=0.023),albumin content(P=0.013),and direct bilirubin content(P=0.018),were also better than those in the PN group.No substantial differences in postoperative complications were found between the groups.Correlation analysis indicated that abdominal infection and operation time may relate to time to first defecation.Linear regression analysis demonstrated a considerable association between EN feeding and shorter time to first defecation.Abdominal infection and an operation time>2 hours may be risk factors for prolonged time to first defecation.CONCLUSION EN substantially promotes the recovery of gastrointestinal function after CIA in neonates and can improve clinical outcomes in children.Future research should explore optimal EN practices to enhance clinical application and child health.展开更多
BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has ne...BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has never been reported.CASE SUMMARY A 42-year-old female with a benign neurilemmoma of the duodenum underwent PD.Her superior mesenteric vein(SMV)was injured during surgery and required reconstruction.She experienced SMV thrombosis and bowel gangrene requiring massive bowel resection.Consequently,she developed short gut syndrome and an enterocutaneous fistula,leading to prolonged hospitalization for wound care and total parenteral nutrition(TPN)support.She was referred to our hospital for ITx evaluation.Upon arrival,she had cholestasis due to IF-associated liver disease.After gastrointestinal(GI)reconstruction to restore GI continuity,she was eligible for multi-visceral transplantation(MVTx).The anticipated allograft included the stomach,small intestine,liver,pancreas,and duodenum.She found a suitable donor after two years of waiting.The MVTx procedure was straightforward with signs of immediate function.Enteral feeding was initiated on postoperative day(POD)7.TPN weaning was achieved on POD 28,and the patient was discharged on POD 69.Two years post-MVTx,she is healthy with excellent graft function.To our knowledge,this is the first case report on MVTx as the treatment for fatal post-PD complications and also the first reported case of ITx in Southeast Asia.CONCLUSION Post-PD IF is rare and lethal.Intestinal and MVTx might be a rescue treatment for IF after GI surgery in eligible patients.展开更多
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 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.
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.
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.
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 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Supported by Guangdong Provincial Medical Research Fund General Program,No.B2025209Guangzhou Science and Technology Program Project,No.2025A03J3269.
文摘Intestinal transplantation(ITx)has emerged as a pivotal life-saving intervention for patients with irreversible intestinal failure unresponsive to conventional medical and nutritional therapies.Despite its growing clinical acceptance,ITx remains among the most immunologically complex and technically demanding procedures in the field of solid organ transplantation.This review comprehensively summarizes the historical evolution,clinical indications,and advancements in surgical techniques,with emphasis on innovations in vascular anastomosis,multivisceral transplantation,and ex vivo preservation.Special attention is given to the unique immunological challenges of ITx,including bidirectional immune responses-host-vs-graft and graft-vs-host disease-immune-microbiota interactions,and the distinct roles of key immune cells.Pediatric and adult recipients exhibit divergent etiologies,immune responses,and complication profiles,necessitating individualized approaches.Although novel immunotherapeutic strategies and bioengineering innovations have improved short-term outcomes,chronic rejection,graft dysfunction,and immunosuppressive toxicity remain significant barriers.Looking ahead,future directions should prioritize precision immunomodulation,microbiome-targeted therapies,and integrated platforms for gene editing,3D bioprinting,and immune monitoring.Through multidisciplinary collaboration and translational research,ITx is poised to evolve from a high-risk salvage therapy into a personalized,sustainable solution that enhances long-term survival and patient quality of life.
基金National Natural Science Foundation of China(32372830 and 31972528).
文摘Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbio-sis.However,it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.Results In this study,we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score,and elevated levels of lipopolysaccharide(LPS)and D-lactate(D-LA)compared to healthy piglets.Subsequently,we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets.Diarrheal piglets demonstrated intestinal microbiota dysbiosis,characterized pri-marily by a higher Firmicutes to Bacteroidota ratio,a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri,and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron.Functional pro-filing of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes(KEGG)data was performed,and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diar-rhea.Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets.Furthermore,we explored the effects of dietary indole-3-aldehyde(IAld),a key tryptophan metabolite,on intestinal development and gut barrier function in weaned piglets.Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell(ISC)expansion in piglets.The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.Conclusions These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intesti-nal development by promoting ISC expansion in weaned piglets.
文摘The role of small bowel capsule endoscopy (CE) in suspected small bowel bleedingis well established and current European and other international guidelinesposition it as the first line test after negative bidirectional endoscopies. Insuspected mid-lower gastrointestinal bleeding (MLGIB) the diagnostic yield ofcolonoscopy is poor and may cause a delay in detecting small bowel disease. Acrucial aspect of small bowel capsule endoscope performance is the timing of theprocedure, the interval between the bleeding episode and capsule ingestion isinversely related to the diagnostic yield as confirmed by a recent meta-analysis.Currently the ongoing advances achieved by video CE in particular to evaluateboth small bowel and colon in a single test using double headed capsules, raisesquestions regarding the position of pan intestinal capsule in the current algorithmto investigate patients presenting with suspected MLGIB ahead of colonoscopy.Early evidence suggests pan intestinal capsule could fit well as a diagnostic“filter” test in this cohort of patients, thereby reserving invasive conventionalcolonoscopy or device assisted enteroscopy as therapeutics options only. The recentdevelopment of magnetically controlled CE and a blood sensing capsule pushthe boundaries of CE even further in patients presenting with suspected gastrointestinalbleeding. This review will discuss the current available evidence andfuture directions of CE in suspected MLGIB.
基金financially supported by the National Key Research and Development Program of China(2022YFF1100402)National Center of Technology Innovation for Dairy(2022-Open subject-11)+1 种基金Young Elite Scientist Sponsorship Program by CAST(YESS20200271)the National Natural Science Foundation of China(32101919)。
文摘2'-Fucosyllactose(2'-FL)shows the potential to support intestinal health as a natural prebiotic that bridges the gap between infant formula feeding and breastfeeding.However,the effect and mechanism of 2'-FL in improving intestinal permeability are not clear.In this study,we constructed human microbiota-associated(HMA)mouse models by colonizing healthy infant feces in mice with antibiotic-depleted intestinal microbiota.The protective effect of 2'-FL on the intestinal permeability was explored using the HMA mouse models,and the combination of metagenomics was used to analyze the possible mechanisms by which the microorganisms reduced the intestinal permeability.The results showed that 2'-FL decreased the concentration of markers of intestinal permeability(enterotoxin and diamine oxidase(DAO))and increased the expression levels of tight junctions(occludin and claudin).Metagenomics revealed the enrichment of Bifidobacterium and increased the expression of glycoside hydrolases(GHs),including GH31,GH28,and GH5.In conclusion,2'-FL strengthened intestinal permeability function by improving microbiota composition to control the translocation of harmful substance.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
文摘BACKGROUND Rotavirus(RV),a primary cause of diarrhea-related mortality in 2021,has been shown to damage intestinal epithelial cells while upregulating intestinal stem cells(ISCs)activities.ISCs within the crypt niche drive the continuous self-renewal of intestinal epithelium,preserving its barrier functions.Paneth cells secrete antimicrobial peptide and signaling molecules within the intestine crypt,thereby playing a crucial role in intestinal immune defense and providing ISCs functional support.However,the regulatory function of Paneth cells under pathological conditions,such as RV infection,remains unclear.AIM To determine the impact of RV infection on Paneth cells and how Paneth cells regulate ISCs during intestinal injury repair.METHODS We constructed a reference genome for the RV enteric cytopathogenic human orphan virus strain and reanalyzed published single-cell RNA sequencing data to investigate Paneth cell responses to RV-induced intestinal injury.We derived Paneth-ISC communication networks using CellChat,tracked ISC differentiation with pseudotime analysis,and validated our findings in leucine-rich repeat-containing G protein-coupled receptor 5-enhanced green fluorescent protein-internal ribosomal entry site-Cre recombinase estrogen receptor variant 2 mice and organoids via immunofluorescence,flow cytometry,and reverse transcription quantitative polymerase chain reaction.RESULTS We found that RV directly infects Paneth cells,leading to a reduction in mature Paneth cells and an increase in kallikrein 1-high immature Paneth cells.Paneth-ISC communication was significantly enhanced.In particular,the bone morphogenic protein 7(BMP7)-activin A receptor type 2B/BMP receptor type 1A-Smad pathway was upregulated post-infection,suggesting that Paneth cells suppress excessive ISC proliferation.Functional validation confirmed activation of this pathway.CONCLUSION Paneth cells regulate ISC proliferation during RV infection by activating BMP7 signaling,limiting excessive stem cell expansion and preserving crypt homeostasis for effective epithelial repair.
文摘BACKGROUND Small intestinal bacterial overgrowth(SIBO)is suspected and excluded frequently in functional gastrointestinal(GI)disorders.Children presenting with various esophago-gastro-duodenal(upper GI)symptoms are rarely subjected to investig-ations for SIBO.AIM To estimate the frequency of SIBO in children having functional upper GI sym-ptoms(as cases)and to compare the result of the SIBO status to that of the con-trols.METHODS Children aged 6 to 18 who presented with upper GI symptoms were selected for the study.All children were subjected to upper GI endoscopy before being advised of any proton pump inhibitors(PPIs).Children with normal endoscopy were assigned as cases,and children having any endoscopic lesion were design-ated as controls.Both groups were subjected to a glucose-hydrogen breath test by Bedfont Gastrolyser.RESULTS A total of 129 consecutive children who were naive to PPIs and had normal ba-seline investigations were included in the study.Among them,67 patients had endoscopic lesions and served as the control group,with six cases being excluded due to the presence of Helicobacter pylori in gastric biopsies.Sixty-two children with normal endoscopy results formed the case group.In the case group,35 children(59%)tested positive for hydrogen breath tests,compared to 13 children(21%)in the control group.The calculated odds ratio was 5.38(95%confidence interval:2.41-12.0),which was statistically significant.Further analysis of symptoms revealed that nausea,halitosis,foul-smelling eructation,and epigastric fullness were positive predictors of SIBO.CONCLUSION It is worthwhile to investigate and treat SIBO in all children presenting with upper GI symptoms that are not explained by endoscopy findings.
文摘BACKGROUND Congenital intestinal atresia(CIA)is a common intestinal malformation in the neonatal period,and surgery is currently the main treatment method.The choice of postoperative feeding is crucial for the recovery of gastrointestinal function in children.AIM To compare and analyze the effects of different postoperative feeding methods on gastrointestinal function reconstruction in newborns with CIA.METHODS Twenty-six children diagnosed with neonatal CIA,treated with minimally invasive surgery at Shijiazhuang Maternal and Child Health Hospital between January 2021 and May 2024,were selected for this single-center prospective randomized controlled study.They were divided into two groups using envelope randomization:Enteral nutrition(EN)group(n=13)and parenteral nutrition(PN)group(n=13).Baseline and clinical characteristics were collected,and recovery time of bowel sounds and time to first defecation were used as evaluation indices for gastrointestinal functional reconstruction.Differences between the groups were analyzed using t-test,χ2 test,and Fisher’s exact test.Spearman’s correlation tests and linear regression models were employed to analyze factors influencing time to first defecation.RESULTS The time to bowel sound recovery(51.54 vs 65.85,P=0.013)and first defecation(58.15 vs 76.62,P<0.001)was shorter in the EN group compared to the PN group.Clinical improvements in the EN group,including discharge weight(P=0.044),hospital stay(P=0.027),white blood cell count(P=0.023),albumin content(P=0.013),and direct bilirubin content(P=0.018),were also better than those in the PN group.No substantial differences in postoperative complications were found between the groups.Correlation analysis indicated that abdominal infection and operation time may relate to time to first defecation.Linear regression analysis demonstrated a considerable association between EN feeding and shorter time to first defecation.Abdominal infection and an operation time>2 hours may be risk factors for prolonged time to first defecation.CONCLUSION EN substantially promotes the recovery of gastrointestinal function after CIA in neonates and can improve clinical outcomes in children.Future research should explore optimal EN practices to enhance clinical application and child health.
文摘BACKGROUND Post-pancreaticoduodenectomy(PD)intestinal failure(IF)is rare and associated with poor outcomes.To our knowledge,the role of intestinal transplantation(ITx)as a rescue treatment for this complication has never been reported.CASE SUMMARY A 42-year-old female with a benign neurilemmoma of the duodenum underwent PD.Her superior mesenteric vein(SMV)was injured during surgery and required reconstruction.She experienced SMV thrombosis and bowel gangrene requiring massive bowel resection.Consequently,she developed short gut syndrome and an enterocutaneous fistula,leading to prolonged hospitalization for wound care and total parenteral nutrition(TPN)support.She was referred to our hospital for ITx evaluation.Upon arrival,she had cholestasis due to IF-associated liver disease.After gastrointestinal(GI)reconstruction to restore GI continuity,she was eligible for multi-visceral transplantation(MVTx).The anticipated allograft included the stomach,small intestine,liver,pancreas,and duodenum.She found a suitable donor after two years of waiting.The MVTx procedure was straightforward with signs of immediate function.Enteral feeding was initiated on postoperative day(POD)7.TPN weaning was achieved on POD 28,and the patient was discharged on POD 69.Two years post-MVTx,she is healthy with excellent graft function.To our knowledge,this is the first case report on MVTx as the treatment for fatal post-PD complications and also the first reported case of ITx in Southeast Asia.CONCLUSION Post-PD IF is rare and lethal.Intestinal and MVTx might be a rescue treatment for IF after GI surgery in eligible patients.
