Probiotics are a kind of living microorganisms added into food or drug,which are beneficial to our health.Probiotics can regulate the balance of microecosystem in intestine.Recently,people have paid more attention to ...Probiotics are a kind of living microorganisms added into food or drug,which are beneficial to our health.Probiotics can regulate the balance of microecosystem in intestine.Recently,people have paid more attention to the effect on the intestinal microecology.This article mainly made a review on the mechanism and application of probiotics.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
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
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
OBJECTIVE:To explore the treatment efficacy of integrated Chinese medicine(Chaihu Shugan San,柴胡疏肝散,CSS)and western therapy in the treatment of adhesive intestinal obstruction(AIO),to provide new ideas for the man...OBJECTIVE:To explore the treatment efficacy of integrated Chinese medicine(Chaihu Shugan San,柴胡疏肝散,CSS)and western therapy in the treatment of adhesive intestinal obstruction(AIO),to provide new ideas for the management of the disease.METHODS:In our single-blind randomized controlled study,120 patients with AIO who were hospitalized in The Affiliated Hospital of China West Normal University Nan Chong Gaoping District People's Hospital from January 2021 to June 2022 and met the inclusion criteria were categorized into the treatment group and the control group.Patients from the control group were administered basic Western Medicine therapy,whereas patients from the treatment group were administered basic Western Medicine therapy plus CSS by gastric tube injection.Subsequently,the time to first anal exhaustion and defecation,time to relief of abdominal distension and pain,days of hospitalization,Traditional Chinese Medicine(TCM)symptom scores,interleukin-6(IL-6),C-reactive protein(CRP)and procalcitonin(PCT)levels in the 2 groups were recorded and compared.RESULTS:The comparison of clinical efficacy of the treatment group were better than the control group.The TCM symptom score was considerably lower in the treatment group;the inflammation indicators CRP,IL-6,and PCT also decreased statistically when comparing the control group.Furthermore,there were significantly reduced in the time to first exhaustion,time to first defecation,time to relief of abdominal pain and distension,and days of hospitalization in the treatment group versus the control group.CONCLUSION:CSS could suppress the inflammatory reaction,reduce days of hospitalization,relieve clinical symptoms in AIO patients with reliable efficacy and high safety and is worthy of clinical application.展开更多
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clost...Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.展开更多
The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to...The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.展开更多
BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD al...BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier 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
Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(EC...Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(ECM)genes and microRNAs(miRNAs)in IIRI have garnered widespread attention.This review aims to systematically summarize the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI.First,we review the molecular mechanisms of IIRI,focusing on the dual role of the ECM in tissue injury and repair processes.The expression changes and functions of ECM components such as collagen,elastin,and matrix metalloproteinases during IIRI progression are deeply analyzed.Second,we systematically summarize the regulatory roles of miRNAs in IIRI,particularly the mechanisms and functions of miRNAs such as miR-125b and miR-200a in regulating inflammation,apoptosis,and ECM remodeling.Additionally,this review discusses potential diagnostic biomarkers and treatment strategies based on ECM genes and miRNAs.We extensively evaluate the prospects of miRNA-targeted therapy and ECM component modulation in preventing and treating IIRI,emphasizing the clinical translational potential of these emerging therapies.In conclusion,the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI provides new directions for further research,necessitating additional clinical and basic studies to validate and expand these findings for improving clinical outcomes in IIRI patients.展开更多
Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying m...Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.展开更多
[Objective]To explore the protective effect of selenomethionine(Se-Met)on oxidative stress and intestinal barrier damage in mice infected with porcine deltacoronavirus(PDCoV)and the potential regulatory mechanism.[Met...[Objective]To explore the protective effect of selenomethionine(Se-Met)on oxidative stress and intestinal barrier damage in mice infected with porcine deltacoronavirus(PDCoV)and the potential regulatory mechanism.[Methods]Forty female C57 mice were randomly grouped as follows:control,Se-Met(0.3 mg/kg Se),PDCoV,and Se-Met+PDCoV(0.3 mg/kg Se).After being fed with or without Se-Met for 23 days,the mice in the PDCoV group and the Se-Met+PDCoV group were administrated with 300μL suspension of PDCoV HNZK-02-P5 strain(1×10^(6)TCID50)by gavage,while those in the other two groups were administered with the same volume of Dulbecco’s Modified Eagle Medium(DMEM).All the mice were observed daily for clinical signs,food intake,and body weight changes until day 28.At five days post-inoculation(dpi),intestinal tissues were collected and PDCoV titers were determined.Hematoxylin staining and eosin staining were used to monitor pathological changes in intestinal tissues.Oxidative stress-related indicators such as malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)were investigated.The level of ROS in the jejunum tissue was measured via a 2′,7′-dichlorofluorescein diacetate(DCFH-DA)probe.Immunofluorescence was used to analyze the changes of small intestinal tight junction proteins(ZO-1 and Occludin).The mRNA levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,and IL-10),intestinal tight junction proteins(ZO-1 and Occludin),and the Nrf2 signaling pathway-associated factors(Nrf2,HO-1,and NQO1)were determined by RT-qPCR.Western blotting was employed to assess the protein levels of factors related to the Nrf2 signaling pathway.[Results]The results of body weight,food intake,pathological examination,and viral RNA titers in different intestinal tissues revealed that Se-Met might increase the body weight,decrease viral titers in intestinal tissues,and attenuate PDCoV-induced structural damage of intestinal villi in PDCoV-infected mice.Se-Met attenuated PDCoV-induced inflammation by lowering the mRNA levels of major inflammatory cytokines,such as IL-1β,IL-6,and TNFαin the jejunum.Se-Met ameliorated PDCoV-induced intestinal mucosal barrier damage by up-regulating the mRNA levels of ZO-1 and Occludin in the jejunum.Se-Met ameliorated PDCoV-induced oxidative stress by decreasing the levels of ROS and MDA and increasing the levels of GSH-PX and SOD in the jejunum.Se-Met inhibited PDCoV-induced oxidative stress by activating the Nrf2 signaling pathway.[Conclusion]Se-Met may attenuate the intestinal injury in mice infected with PDCoV by activating the Nrf2 signaling pathway,which provides a theoretical basis for the prevention and treatment of PDCoV infection.展开更多
Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoti...Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoting susceptibility to lung diseases.The development and progression of lung cancer,as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites,which influence immunological and inflammatory responses.During abnormal proliferation,non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways.Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP,carbon,and nitrogen sources,respectively,providing optimal conditions for tumor cell proliferation,invasion,and immune escape.This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer,and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence,development,and immunotherapy of non-small cell lung cancer,in order to provide new ideas for precision treatment of lung cancer patients.展开更多
Lithopedion is a rare clinical situation characterised by the calcification of a foetus that has died during an ectopic pregnancy, usually in the abdominal cavity. It occurs in 1.5 to 2% of ectopic pregnancies. It can...Lithopedion is a rare clinical situation characterised by the calcification of a foetus that has died during an ectopic pregnancy, usually in the abdominal cavity. It occurs in 1.5 to 2% of ectopic pregnancies. It can be asymptomatic for several years. However, various complications can occur that lead to diagnosis. The authors report a case of lithopedion complicated by acute intestinal obstruction in a 24-year-old woman in her first pregnancy. This complication occurred after 12 months of amenorrhoea. A mass containing a calcified foetus was removed by laparotomy.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
Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent im...Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.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
Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The...Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The pathogenesis of IBD is closely related to host genetic susceptibility,disorders of the intestinal flora,damage to the intestinal mucosal barrier,and abnormal intestinal mucosal immunity.On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD,the influence of genetics on the intestinal barrier and intestinal microbiota;the metagenomics,metatranscriptomics,and metabolomics of the intestinal microbiota involved in IBD;and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.展开更多
文摘Probiotics are a kind of living microorganisms added into food or drug,which are beneficial to our health.Probiotics can regulate the balance of microecosystem in intestine.Recently,people have paid more attention to the effect on the intestinal microecology.This article mainly made a review on the mechanism and application of probiotics.
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.
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Nanchong City Science and Technology Plan Project:the Application of Tongli Shugan Liqi Method in the Treatment of Adhesive Intestinal Obstruction and its Effect on Inflammatory Indicators Interleukin-6,C-reactive protein and Procalcitonin(21YFZJ0108)。
文摘OBJECTIVE:To explore the treatment efficacy of integrated Chinese medicine(Chaihu Shugan San,柴胡疏肝散,CSS)and western therapy in the treatment of adhesive intestinal obstruction(AIO),to provide new ideas for the management of the disease.METHODS:In our single-blind randomized controlled study,120 patients with AIO who were hospitalized in The Affiliated Hospital of China West Normal University Nan Chong Gaoping District People's Hospital from January 2021 to June 2022 and met the inclusion criteria were categorized into the treatment group and the control group.Patients from the control group were administered basic Western Medicine therapy,whereas patients from the treatment group were administered basic Western Medicine therapy plus CSS by gastric tube injection.Subsequently,the time to first anal exhaustion and defecation,time to relief of abdominal distension and pain,days of hospitalization,Traditional Chinese Medicine(TCM)symptom scores,interleukin-6(IL-6),C-reactive protein(CRP)and procalcitonin(PCT)levels in the 2 groups were recorded and compared.RESULTS:The comparison of clinical efficacy of the treatment group were better than the control group.The TCM symptom score was considerably lower in the treatment group;the inflammation indicators CRP,IL-6,and PCT also decreased statistically when comparing the control group.Furthermore,there were significantly reduced in the time to first exhaustion,time to first defecation,time to relief of abdominal pain and distension,and days of hospitalization in the treatment group versus the control group.CONCLUSION:CSS could suppress the inflammatory reaction,reduce days of hospitalization,relieve clinical symptoms in AIO patients with reliable efficacy and high safety and is worthy of clinical application.
基金supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金supported by China Agriculture Research System Program(Project No.CARS-41-G04)。
文摘Background Necrotic enteritis(NE)in broiler chickens leads to significant economic losses in poultry production.This study examined the inhibitory effects of usnic acid and tannic acid on coccidia,sporozoite,and Clostridium perfringens and assessed their influence on growth performance and intestinal health in NE-challenged broilers through in vitro and in vivo experiments.Methods The in vitro experiment included 5 treatment groups:the negative control(NC),2μmol/L diclazuril(DZ),30μmol/L usnic acid(UA),90μmol/L tannic acid(TA),and 15μmol/L usnic acid^(+)45μmol/L tannic acid(UTA)groups.The in vivo experiment involved 320 broilers divided into four groups:PC(NE-challenged),SA(500 mg/kg salinomycin premix^(+)NE-challenged),UA(300 mg/kg usnic acid^(+)NE-challenged),and UTA(300 mg/kg usnic acid^(+)500 mg/kg tannic acid^(+)NE-challenged)groups.Results In the in vitro study,the UA,TA,and UTA treatments significantly increased apoptosis in coccidian oocysts and sporozoites,lowered the mitochondrial membrane potential(P<0.05),and disrupted the oocyst structure compared with those in the NC group.UA and TA had inhibitory effects on C.perfringens,with the strongest inhibition observed in the UTA group.The in vivo results demonstrated that the SA group presented significantly improved growth performance on d 13,21,and 28(P<0.05),whereas the UA and UTA groups presented improvements on d 13 and 21(P<0.05).The SA,UA,and UTA treatments reduced the intestinal lesion scores by d 28 and the fecal coccidian oocyst counts from d 19 to 21(P<0.05).Compared with the PC group,the UA and UTA groups presented lower intestinal sIgA levels and CD8^(+)cell percentages(P<0.05),with a trend toward a reduced CD3^(+)cell percentage(P=0.069).The SA,UA,and UTA treatments significantly reduced the serum diamine oxidase activity,crypt depth,and plateletderived growth factor levels in the intestinal mucosa while increasing the villus height to crypt depth ratio and number of goblet cells(P<0.05).The UTA treatment also significantly increased the acetate and butyrate concentrations in the cecum(P<0.05).With respect to the gut microbiota,significant changes inβdiversity in the ileum and cecum were observed in the SA,UA,and UTA groups,indicating that the microbial community compositions differed among the groups.Romboutsia dominated the SA group,Bacillales dominated the UA group,and Lactobacillales and Lachnospirales dominated the UTA group in the ileal microbiota.In the cecal microbiota,Lactobacillus,Butyricicoccus,and Blautia abundances were significantly elevated in the UTA group(P<0.05).Conclusion Usnic acid and tannic acid induce apoptosis in coccidia and sporozoites by lowering the mitochondrial membrane potential.Both usnic acid alone and in combination with tannic acid alleviate NE-induced adverse effects in broilers by modulating intestinal immunity,altering the microbial composition,and improving intestinal barrier function.Compared with usnic acid alone,the combination of usnic acid and tannic acid had superior effects,providing a promising basis for the development of effective feed additive combinations.
基金supported by the fund for the Project of the National Key Research and Development Program of China(2024YFD1300203)Project support was provided by the Fund opened from Key Laboratory of Fujian Universities Preventive Veterinary Medicine and Biotechnology,Longyan University(grant No.2021KF01)the Cyanine Project of Yangzhou University(2020)。
文摘The intestinal tract,a complex organ responsible for nutrient absorption and digestion,relies heavily on a balanced gut microbiome to maintain its integrity.Disruptions to this delicate microbial ecosystem can lead to intestinal inflammation,a hallmark of inflammatory bowel disease(IBD).While the role of the gut microbiome in IBD is increasingly recognized,the underlying mechanisms,particularly those involving endoplasmic reticulum(ER)stress,autophagy,and cell death,remain incompletely understood.ER stress,a cellular response to various stressors,can trigger inflammation and cell death.Autophagy,a cellular degradation process,can either alleviate or exacerbate ER stress-induced inflammation,depending on the specific context.The gut microbiome can influence both ER stress and autophagy pathways,further complicating the interplay between these processes.This review delves into the intricate relationship between ER stress,autophagy,and the gut microbiome in the context of intestinal inflammation.By exploring the molecular mechanisms underlying these interactions,we aim to provide a comprehensive theoretical framework for developing novel therapeutic strategies for IBD.A deeper understanding of the ER stress-autophagy axis,the gut microbial-ER stress axis,and the gut microbial-autophagy axis may pave the way for targeted interventions to restore intestinal health and mitigate the impact of IBD.
基金Supported by the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars,No.2022B1515020003the National Natural Science Foundation of China,No.82174369,No.82405397,No.82374442,and No.81973847+2 种基金Postdoctoral Fellowship Program of CPSF No.GZC20233247National Key Clinical Disciplineand the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases,No.2020B1111170004.
文摘BACKGROUND The development of slow transit constipation(STC)is associated with intestinal barrier damage.Huangqi decoction(HQD)is effective in treating STC,but me-chanisms are unclear.AIM To investigate whether HQD alleviates STC by downregulating the nuclear factorκB(NF-κB)signaling pathway and restoring intestinal barrier function.METHODS KM mice were divided into control,model,and HQD treatment groups.Fresh colonic tissues were collected for single-cell RNA sequencing and spatial tra-nscriptome sequencing.The expressions of claudin-1,mucin 2,and NF-κB P65 proteins were detected by immunohistochemistry.In vitro experiments evaluated the effects of HQD on the LS174T cell line.RESULTS HQD improved intestinal motility,restored mucosal epithelium function and morphology.Single-cell RNA sequencing and spatial transcriptome sequencing data showed a reduction in goblet cells,decreased mucin 2 secretion,and activated apoptotic pathways in STC mice.The population of intestinal stem cells was reduced,and proliferation along with Wnt/β-catenin pathways were inhibited.STC also altered the distribution of intestinal cell states,increasing immune-associated Enterocyte_C3.Aberrant NF-κB pathway activation was noted across various cell types.After HQD treatment,NF-κB pathway activity was down-regulated,while cell proliferation pathways were up-regulated,alongside an increase in Enterocyte_C1 related to material transport.Immunocytochemical,Western blot,and immunohistochemistry analyses confirmed NF-κB pathway activation in goblet cells of STC mice,with HQD inhibiting this aberrant activation.CONCLUSION STC involves intestinal mucosal barrier damage.HQD may treat STC by suppressing NF-κB signaling in epithelial cells,restoring intestinal epithelial cell function,and promoting mucosal barrier 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.
基金Supported by Health Science and Technology Programme of Zhejiang Province,No.2022KY1391.
文摘Intestinal ischemia-reperfusion injury(IIRI)is a complex and severe pathophysiological process characterized by oxidative stress,inflammation,and apoptosis.In recent years,the critical roles of extracellular matrix(ECM)genes and microRNAs(miRNAs)in IIRI have garnered widespread attention.This review aims to systematically summarize the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI.First,we review the molecular mechanisms of IIRI,focusing on the dual role of the ECM in tissue injury and repair processes.The expression changes and functions of ECM components such as collagen,elastin,and matrix metalloproteinases during IIRI progression are deeply analyzed.Second,we systematically summarize the regulatory roles of miRNAs in IIRI,particularly the mechanisms and functions of miRNAs such as miR-125b and miR-200a in regulating inflammation,apoptosis,and ECM remodeling.Additionally,this review discusses potential diagnostic biomarkers and treatment strategies based on ECM genes and miRNAs.We extensively evaluate the prospects of miRNA-targeted therapy and ECM component modulation in preventing and treating IIRI,emphasizing the clinical translational potential of these emerging therapies.In conclusion,the diagnostic and therapeutic potential of ECM gene sets and miRNA regulatory networks in IIRI provides new directions for further research,necessitating additional clinical and basic studies to validate and expand these findings for improving clinical outcomes in IIRI patients.
文摘Chemotherapy-induced intestinal mucositis(IM)is a prevalent complication affecting up to 80%of cancer patients undergoing treatment.Current therapies focus on symptomatic relief rather than addressing the underlying mechanism.Recent advances in integrative medicine highlight the potential of traditional Chinese medicine formulations as alternatives or adjuncts to existing therapies.In this context,this editorial discusses the recent results of a study published by Qiu et al,which investigates the multifaceted potential of modified Pulsatilla decoction(PD),a formulation of PD with licorice(Glycyrrhiza uralensis)and Ejiao(Colla corii asini),on 5-fluorouracil-induced IM in mice to alleviate clinical symptoms including diarrhea,weight loss,and intestinal damage.A series of histological,biochemical,bioinformatic,and microbiological assays evaluated body weight,diarrhea scores,inflammatory cytokine profiles,oxidative stress modulation,and microbiota composition.The findings indicated a reduction in diarrhea and oxidative stress,as well as an improvement in body weight and intestinal histopathology.Furthermore,the modified PD suppressed the TLR4/MyD88/nuclear factor kappa-B inflammatory pathway and down-regulated key proinflammatory cytokines.Moreover,the study underscores the role of gut microbiota in IM pathogenesis.Modified PD treatment reshaped microbial diversity by promoting beneficial genera such as Bacteroides acidifaciens while suppressing pathogenic species like Salmonella.These findings suggest that the therapeutic effects of the modified PD extend beyond inflammation modulation to encompass microbiome reprogramming and mucosal barrier repair.Although the study provides significant insights,several limitations still prevail.The broader implications of modified PD in gastrointestinal disorders and integrative oncology need further exploration.
文摘[Objective]To explore the protective effect of selenomethionine(Se-Met)on oxidative stress and intestinal barrier damage in mice infected with porcine deltacoronavirus(PDCoV)and the potential regulatory mechanism.[Methods]Forty female C57 mice were randomly grouped as follows:control,Se-Met(0.3 mg/kg Se),PDCoV,and Se-Met+PDCoV(0.3 mg/kg Se).After being fed with or without Se-Met for 23 days,the mice in the PDCoV group and the Se-Met+PDCoV group were administrated with 300μL suspension of PDCoV HNZK-02-P5 strain(1×10^(6)TCID50)by gavage,while those in the other two groups were administered with the same volume of Dulbecco’s Modified Eagle Medium(DMEM).All the mice were observed daily for clinical signs,food intake,and body weight changes until day 28.At five days post-inoculation(dpi),intestinal tissues were collected and PDCoV titers were determined.Hematoxylin staining and eosin staining were used to monitor pathological changes in intestinal tissues.Oxidative stress-related indicators such as malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-PX)were investigated.The level of ROS in the jejunum tissue was measured via a 2′,7′-dichlorofluorescein diacetate(DCFH-DA)probe.Immunofluorescence was used to analyze the changes of small intestinal tight junction proteins(ZO-1 and Occludin).The mRNA levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,and IL-10),intestinal tight junction proteins(ZO-1 and Occludin),and the Nrf2 signaling pathway-associated factors(Nrf2,HO-1,and NQO1)were determined by RT-qPCR.Western blotting was employed to assess the protein levels of factors related to the Nrf2 signaling pathway.[Results]The results of body weight,food intake,pathological examination,and viral RNA titers in different intestinal tissues revealed that Se-Met might increase the body weight,decrease viral titers in intestinal tissues,and attenuate PDCoV-induced structural damage of intestinal villi in PDCoV-infected mice.Se-Met attenuated PDCoV-induced inflammation by lowering the mRNA levels of major inflammatory cytokines,such as IL-1β,IL-6,and TNFαin the jejunum.Se-Met ameliorated PDCoV-induced intestinal mucosal barrier damage by up-regulating the mRNA levels of ZO-1 and Occludin in the jejunum.Se-Met ameliorated PDCoV-induced oxidative stress by decreasing the levels of ROS and MDA and increasing the levels of GSH-PX and SOD in the jejunum.Se-Met inhibited PDCoV-induced oxidative stress by activating the Nrf2 signaling pathway.[Conclusion]Se-Met may attenuate the intestinal injury in mice infected with PDCoV by activating the Nrf2 signaling pathway,which provides a theoretical basis for the prevention and treatment of PDCoV infection.
基金supported by the Scientific Research Fund Project of Education Department of Yunnan Province,China(No.2024Y386).
文摘Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoting susceptibility to lung diseases.The development and progression of lung cancer,as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites,which influence immunological and inflammatory responses.During abnormal proliferation,non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways.Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP,carbon,and nitrogen sources,respectively,providing optimal conditions for tumor cell proliferation,invasion,and immune escape.This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer,and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence,development,and immunotherapy of non-small cell lung cancer,in order to provide new ideas for precision treatment of lung cancer patients.
文摘Lithopedion is a rare clinical situation characterised by the calcification of a foetus that has died during an ectopic pregnancy, usually in the abdominal cavity. It occurs in 1.5 to 2% of ectopic pregnancies. It can be asymptomatic for several years. However, various complications can occur that lead to diagnosis. The authors report a case of lithopedion complicated by acute intestinal obstruction in a 24-year-old woman in her first pregnancy. This complication occurred after 12 months of amenorrhoea. A mass containing a calcified foetus was removed by laparotomy.
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supported by the Hunan Provincial Science and Technology Major Special Fund(2021SK1020)the Natural Science Foundation of Hunan Province(2023JJ30948)+1 种基金the Health Commission of Hunan Province(202203014687)the International Medical Exchange Cardiovascular Multidisciplinary Integrated Thinking Research Foundation(Z-2016-23-2101-20),China.
文摘Objective:In addition to dyspnea and edema,gastrointestinal discomfort is common among patients with heart failure(HF).Reduced cardiac output can lead to inadequate perfusion of the intestinal mucosa and subsequent impairment of the intestinal barrier.Levosimendan,a novel inotropic agent,binds to cardiac troponin C to enhance calcium sensitivity,activates ATP-dependent potassium channels in cardiomyocytes and vascular smooth muscle cells,exerts positive inotropic and vasodilatory effects,and reduces free radical generation,thereby improving systemic hemodynamics including intestinal circulation.However,clinical evidence regarding its protective effects on the intestinal barrier in HF patients remains limited,and the underlying mechanisms require further clarification.This study aims to investigate whether levosimendan confers protective effects on the intestinal barrier in HF patients and to explore its potential mechanisms.Methods:Network pharmacology was first used to analyze potential mechanisms of levosimendan in treating intestinal barrier dysfunction among HF patients.A total of 62 hospitalized patients with acute exacerbation of HF with reduced ejection fraction(HFrEF)were enrolled based on echocardiographic left ventricular ejection fraction.According to clinical medication regimens,patients were assigned to a conventional treatment group(n=31)or a levosimendan treatment group(n=31).The conventional treatment group received standard anti-HF therapy,while the levosimendan treatment group received levosimendan in addition to standard therapy.Enzyme-linked immunosorbent assays were used to measure plasma levels and changes in the intestinal-barrier proteins zonulin,intestinal fatty acid binding protein(I-FABP),proinflammatory cytokines[interleukin(IL)-17,IL-6,and tumor necrosis factor(TNF)-α],anti-inflammatory cytokine IL-10,and N-terminal probrain natriuretic peptide(NT-proBNP).Improvements in cardiac function and gastrointestinal symptoms were evaluated using the Kansas City Cardiomyopathy Questionnaire(KCCQ)and the Gastrointestinal Symptom Rating Scale(GSRS).Results:Network pharmacology indicated that the effects of levosimendan on intestinal barrier dysfunction in HF patients may involve inflammation-related pathways such as IL-17 and TNF.Clinically,after treatment,zonulin decreased by 32.94 ng/mL in the levosimendan treatment group versus 15.05 ng/mL in the conventional treatment group(P<0.05).I-FABP decreased by 6.97 pg/mL in the levosimendan treatment group but increased by 35.16 pg/mL in the conventional treatment group(P<0.05).IL-6,IL-17,and TNF-αdecreased by 1.11 pg/mL,1.21 pg/mL,and 2.83 pg/mL,respectively,in the levosimendan treatment group,whereas they increased by 7.68 pg/mL,0.67 pg/mL,and 2.38 pg/mL in the conventional treatment group(all P<0.05).IL-10 decreased by 24.48 pg/mL in the conventional treatment group but increased by 24.98 pg/mL in the levosimendan treatment group(P<0.05).NT-proBNP increased by 7.35 pg/mL in the conventional treatment group but decreased by 4.73 pg/mL in the levosimendan treatment group(P<0.05).KCCQ scores increased by 0.36 in the conventional treatment group and 1.86 in the levosimendan treatment group,GSRS scores decreased by 1.00 in the conventional treatment group and 2.40 in the levosimendan treatment group,respectively,but the differences were not statistically significant(both P>0.05).Conclusion:Levosimendan not only improves HF and gastrointestinal symptoms in hospitalized patients with acute exacerbation of HFrEF but also reduces plasma intestinal barrier factor levels.These effects may be associated with decreased plasma proinflammatory cytokines and increased anti-inflammatory cytokines after treatment,potentially involving IL-17 and TNF signaling pathways.
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.
基金Supported by the National Natural Science Foundation of China,No.82574996Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+3 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.2025SF-YBXM-498the“Nursery Cultivation Plan”Project of Shaanxi Provincial Academy of Chinese Medicine and Shaanxi Provincial Hospital of Traditional Chinese Medicine,No.2025-04the Fifth Batch of Outstanding Clinical Talents in Traditional Chinese Medicine Project of Shaanxi Province.
文摘Inflammatory bowel disease(IBD),a chronic disorder characterized by intestinal inflammation and mucosal damage,includes mainly Crohn’s disease and ulcerative colitis.However,the cause of its onset remains unclear.The pathogenesis of IBD is closely related to host genetic susceptibility,disorders of the intestinal flora,damage to the intestinal mucosal barrier,and abnormal intestinal mucosal immunity.On the basis of the progress in research on the structure of the intestinal microbiota involved in IBD,the influence of genetics on the intestinal barrier and intestinal microbiota;the metagenomics,metatranscriptomics,and metabolomics of the intestinal microbiota involved in IBD;and treatments such as probiotics and fecal microbiota transplantation are important for the future treatment of IBD and the development of drugs for effective treatment.
