Intestinal immune homeostasis plays a critical role in the pathogenesis of food allergy.However,the association between intestinal microenvironment factors and food allergy severity is not well studied.In this study,w...Intestinal immune homeostasis plays a critical role in the pathogenesis of food allergy.However,the association between intestinal microenvironment factors and food allergy severity is not well studied.In this study,we established a gluten allergy(GA)BALB/c mouse model and revealed the intestinal luminal factor-mediated alterations in phenotypes and endotypes of GA,combined with untargeted metabolomic profiling of the colonic contents.Our results showed that gluten sensitization induced severe allergic responses in BALB/c mice,characterized by exacerbated clinical allergic and diarrheal symptoms,increased histamine,elevated gluten-specific immunoglobulin(Ig)E and IgG2a levels,and increased mast cell degranulation.In response to GA,T-cell balance was disrupted,with aberrant production of interleukin(IL)-4,interferon(IFN)-γ,IL-10,and IL-2 in the spleen.GA led to a disrupted intestinal microenvironment homeostasis,including increased pH and water content,impaired intestinal antioxidant capacity and epithelial barrier function,decreased short-chain fatty acid production,and microbial dysbiosis,which was strongly correlated with GA severity.By metabolomic profiling,we found 29 differential expressed metabolites(DEMs)associated with GA,with 9 down-regulated and 20 up-regulated.A total of 11 out of all DEMs were classified into dipeptides,and 10 of them were up-regulated in the GA mice.Pathway enrichment analysis showed that most of the DEMs were enriched into the bile secretion metabolic route.展开更多
Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflamm...Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflammation,as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously.In this study,a novel drug delivery system based on a metal polyphenol network(MPN)was constructed via metal coordination between epigallocatechin gallate(EGCG)and Fe^(3+).Curcumin(Cur),an active polyphenolic compound,with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN.The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical(O_(2)•-)as well as hydroxyl radical(⋅OH).By hitchhiking yeast microcapsule(YM),Cur-MPN was then encapsulated into YM to obtain CM@YM.Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon.When administered orally,CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS,reducing pro-inflammatory cytokines,and regulating the polarization of macrophages to M1,thus restoring barrier function and maintaining intestinal homeostasis.Importantly,CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids(SCFA)(such as acetic acid,propionic acid,and butyric acid).Collectively,with excellent biocompatibility,our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.展开更多
BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no s...BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.展开更多
The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maint...The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function—key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.展开更多
The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known a...The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.展开更多
Cholestatic liver disease(CSLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)are both associated with abnormal bile acid(BA)metabolism and have a steadily increasing incidence and prevalence world...Cholestatic liver disease(CSLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)are both associated with abnormal bile acid(BA)metabolism and have a steadily increasing incidence and prevalence worldwide.BAs are amphiphilic cholesterol metabolites that are pivotal in the regulation of their own biosynthesis as well as gut microbiota,indirectly affecting both host immunity and metabolic homeostasis.Conversely,the composition and function of BAs,including their reabsorption and excretion,are regulated by gut microbiota.Thus,regulating gut microbiota or targeting BA metabolic pathways is expected to provide novel strategies for the treatment of liver diseases.The present review focuses on elucidating the critical roles of the gut microbiota-BA axis in CSLD and MASLD and its potential as a therapeutic target.First,we clarify the roles of gut microbiota,BAs,and BA receptors,mainly farnesoid X receptor(FXR)and G protein-coupled BA receptor 1(TGR5),in the modulation of hepatic glucose,lipid,and amino acid metabolism and intestinal barrier function,which effectively maintains the balance of the host immunoinflammatory response,as well as different cell death pathways.We also summarize recent preclinical and clinical studies involving the gut microbiota-BA axis.Subsequently,we emphasize the indirect regulation of BA metabolism by targeting gut microbiota through dietary interventions,fecal microbiota transplantation(FMT),and bacteriophage therapy and direct regulation of BA signaling by targeting secondary BAs,BA receptor agonists(fibroblast growth factor[FGF]19/21),and inhibitors of BA transporters(apical sodium-dependent BA transporter[ASBT],sodium taurocholate co-transporting polypeptide[NTCP]).Finally,we summarize and discuss mainly nanoparticle-based therapeutic strategies for modulating BA metabolism and the composition and function of the gut microbiota.Therefore,this review provides new insights to better understand the gut microbiota-BA axis in the context of treating CSLD and MASLD.展开更多
Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several as...Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.展开更多
基金financially supported by the State Key Research and Development Plan(2019YFC1605000).
文摘Intestinal immune homeostasis plays a critical role in the pathogenesis of food allergy.However,the association between intestinal microenvironment factors and food allergy severity is not well studied.In this study,we established a gluten allergy(GA)BALB/c mouse model and revealed the intestinal luminal factor-mediated alterations in phenotypes and endotypes of GA,combined with untargeted metabolomic profiling of the colonic contents.Our results showed that gluten sensitization induced severe allergic responses in BALB/c mice,characterized by exacerbated clinical allergic and diarrheal symptoms,increased histamine,elevated gluten-specific immunoglobulin(Ig)E and IgG2a levels,and increased mast cell degranulation.In response to GA,T-cell balance was disrupted,with aberrant production of interleukin(IL)-4,interferon(IFN)-γ,IL-10,and IL-2 in the spleen.GA led to a disrupted intestinal microenvironment homeostasis,including increased pH and water content,impaired intestinal antioxidant capacity and epithelial barrier function,decreased short-chain fatty acid production,and microbial dysbiosis,which was strongly correlated with GA severity.By metabolomic profiling,we found 29 differential expressed metabolites(DEMs)associated with GA,with 9 down-regulated and 20 up-regulated.A total of 11 out of all DEMs were classified into dipeptides,and 10 of them were up-regulated in the GA mice.Pathway enrichment analysis showed that most of the DEMs were enriched into the bile secretion metabolic route.
基金supported by the National Natural Science Foundation of China(Nos.52103183,32360176)the Shaanxi Province Key Research and Development Program(No.2023-YBSF-072)+3 种基金the Natural Science Basic Research Program of Shaanxi(Nos.2021JQ-382,2024JC-YBMS-664)the Fundamental Research Funds for the Central Universities,China(No.xtr052023008)the Innovation Team of Xi’an Medical University(No.2021TD15)the Young Talent Support Plan of Xi’an Jiaotong University,China(No.YX6J001).
文摘Ulcerative colitis(UC)is characterized by chronic inflammatory processes of the intestinal tract of unknown origin.Current treatments lack understanding on how to effectively alleviate oxidative stress,relieve inflammation,as well as modulate gut microbiota for maintaining intestinal homeostasis synchronously.In this study,a novel drug delivery system based on a metal polyphenol network(MPN)was constructed via metal coordination between epigallocatechin gallate(EGCG)and Fe^(3+).Curcumin(Cur),an active polyphenolic compound,with distinguished anti-inflammatory activity was assembled and encapsulated into MPN to generate Cur-MPN.The obtained Cur-MPN could serve as a robust reactive oxygen species modulator by efficiently scavenging superoxide radical(O_(2)•-)as well as hydroxyl radical(⋅OH).By hitchhiking yeast microcapsule(YM),Cur-MPN was then encapsulated into YM to obtain CM@YM.Our findings demonstrated that CM@YM was able to protect Cur-MPN to withstand the harsh gastrointestinal environment and enhance the targeting and retention abilities of the inflamed colon.When administered orally,CM@YM could alleviate DSS-induced colitis with protective and therapeutic effects by scavenging ROS,reducing pro-inflammatory cytokines,and regulating the polarization of macrophages to M1,thus restoring barrier function and maintaining intestinal homeostasis.Importantly,CM@YM also modulated the gut microbiome to a favorable state by improving bacterial diversity and transforming the compositional structure to an anti-inflammatory phenotype as well as increasing the content of short-chain fatty acids(SCFA)(such as acetic acid,propionic acid,and butyric acid).Collectively,with excellent biocompatibility,our findings indicate that synergistically regulating intestinal microenvironment will be a promising approach for UC.
文摘BACKGROUND Clostridium difficile(C.difficile)infection(CDI)is a rare clinical disease caused by changes in the intestinal microenvironment,which has a variety of causes and a poor prognosis,and for which there is no standardized clinical treatment.CASE SUMMARY A patient experienced recurrent difficulty in bowel movements over the past decade.Recently,symptoms worsened within the last ten days,leading to a clinic visit due to constipation.The patient was subsequently referred to our depart-ment.Preoperatively,the patient was diagnosed with obstructed colon accom-panied by gallstones.Empirical antibiotics were administered both before and after surgery to prevent infection.On the fourth day post-surgery,symptoms of CDI emerged.Stool cultures confirmed the presence of C.difficile DNA.Treatment involved a combination of vancomycin and linezolid,resulting in the patient's successful recovery upon discharge.However,the patient failed to adhere to the prescribed medication after discharge and was discovered deceased during a follow-up two months later.CONCLUSION CDI is the leading cause of nosocomial post-operative care,with limited clinical cases and poor patient prognosis,and comprehensive clinical treatment guidelines are still lacking.This infection can be triggered by a variety of factors,including intestinal hypoxia,inappropriate antibiotic use,and bile acid circulation disorders.In patients with chronic bowel disease and related etiologies,prompt preoperative attention to possible CDI and preoperative bowel preparation is critical.Adequate and prolonged medication should be maintained in the treatment of CDI to prevent recurrence of the disease.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.82370532 and 82341219).
文摘The small intestine is essential for digestion, nutrient absorption, immune regulation, and microbial balance. Its epithelial lining, containing specialized cells like Paneth cells and tuft cells, is crucial for maintaining intestinal homeostasis. Paneth cells produce antimicrobial peptides and growth factors that support microbial regulation and intestinal stem cells, while tuft cells act as chemosensors, detecting environmental changes and modulating immune responses. Along with immune cells such as intraepithelial lymphocytes, innate lymphoid cells, T cells, and macrophages, they form a strong defense system that protects the epithelial barrier. Disruptions in this balance contribute to chronic inflammation, microbial dysbiosis, and compromised barrier function—key features of inflammatory bowel disease, celiac disease, and metabolic syndromes. Furthermore, dysfunctions in the small intestine and immune cells are linked to systemic diseases like obesity, diabetes, and autoimmune disorders. Recent research highlights promising therapeutic strategies, including modulation of epithelial and immune cell functions, probiotics, and gene editing to restore gut health and address systemic effects. This review emphasizes the pivotal roles of small intestinal epithelia and immune cells in maintaining intestinal homeostasis, their involvement in disease development, and emerging treatments for intestinal and systemic disorders.
基金Supported by National Natural Science Foundation of China,No. 82000511 and 82170558Scientific and Technological Projects of Tianjin,No. 21JCQNJC01120+3 种基金Health Science and Technology Project of Tianjin,No. TJWJ2021QN006Scientific Research Project of Tianjin Education Commission,No. 2019KJ197Natural Science Foundation of Zhejiang Province,No. LQ23H050005Scientific Research Project of Zhejiang Provincial Education Department,No. Y202250731
文摘The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.
基金supported by the National Natural Science Foundation of China(No.82325008 and No.82450104).
文摘Cholestatic liver disease(CSLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)are both associated with abnormal bile acid(BA)metabolism and have a steadily increasing incidence and prevalence worldwide.BAs are amphiphilic cholesterol metabolites that are pivotal in the regulation of their own biosynthesis as well as gut microbiota,indirectly affecting both host immunity and metabolic homeostasis.Conversely,the composition and function of BAs,including their reabsorption and excretion,are regulated by gut microbiota.Thus,regulating gut microbiota or targeting BA metabolic pathways is expected to provide novel strategies for the treatment of liver diseases.The present review focuses on elucidating the critical roles of the gut microbiota-BA axis in CSLD and MASLD and its potential as a therapeutic target.First,we clarify the roles of gut microbiota,BAs,and BA receptors,mainly farnesoid X receptor(FXR)and G protein-coupled BA receptor 1(TGR5),in the modulation of hepatic glucose,lipid,and amino acid metabolism and intestinal barrier function,which effectively maintains the balance of the host immunoinflammatory response,as well as different cell death pathways.We also summarize recent preclinical and clinical studies involving the gut microbiota-BA axis.Subsequently,we emphasize the indirect regulation of BA metabolism by targeting gut microbiota through dietary interventions,fecal microbiota transplantation(FMT),and bacteriophage therapy and direct regulation of BA signaling by targeting secondary BAs,BA receptor agonists(fibroblast growth factor[FGF]19/21),and inhibitors of BA transporters(apical sodium-dependent BA transporter[ASBT],sodium taurocholate co-transporting polypeptide[NTCP]).Finally,we summarize and discuss mainly nanoparticle-based therapeutic strategies for modulating BA metabolism and the composition and function of the gut microbiota.Therefore,this review provides new insights to better understand the gut microbiota-BA axis in the context of treating CSLD and MASLD.
基金supported by the National Natural Science Foundation of China (Grants No.82270011 and 81960513)the Scientific Research Foundation of the Affiliated Hospital of Xuzhou Medical University (Grant No.2020KA010)+2 种基金the Priority Academic Program Development of jiangsu Higher Education Institutions (PAPD),and Postgraduate Research&Practice Innovation Program of Jiangsu Province (Grant No.KYCX22_2815)the Natural Science Foundation of Guizhou Provincial Scientific and Technology Department Grant (Grant No. (2022)626)Scientific Research Foundation of Wenzhou Institute,University of Chinese Academy of Sciences.
文摘Inflammatory bowel diseases(IBD)are a group of chronic relapsing gastrointestinal inflammatory diseases with significant global incidence.Although the pathomechanism of IBD has been extensively investigated,several aspects of its pathogenesis remain unclear.Long non-coding RNAs(lncRNAs)are transcripts with more than 200 nucleotides in length that have potential protein-coding functions.LncRNAs play important roles in biological processes such as epigenetic modification,transcriptional regulation and posttranscriptional regulation.In this review,we summarize recent advances in research on IBD-related lncRNAs from the perspective of the overall intestinal microenvironment,as well as their potential roles as immune regulators,diagnostic biomarkers and therapeutic targets or agents for IBD.
