The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by ...The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.展开更多
Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of acti...Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.展开更多
[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural ...[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.展开更多
With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal m...With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic disease with recurrent intestinal inflammation.Although the exact etiology of IBD remains unknown,the accepted hypothesis of the pathogenesis to date is that abno...BACKGROUND Inflammatory bowel disease(IBD)is a chronic disease with recurrent intestinal inflammation.Although the exact etiology of IBD remains unknown,the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors.The role of the gut microbiota,particularly the bidirectional interaction between the brain and gut microbiota,has gradually attracted more attention.AIM To investigate the potential effect of spinal anesthesia on dextran sodium sulfate(DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.METHODS A DSS-induced colitis mice model was established.Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation(FMT)to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.RESULTS We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms,including reduced body weight loss,decreased disease activity index score,improved intestinal permeability and colonic morphology,decreased inflammatory response,and enhanced intestinal barrier functions.Moreover,spinal anesthesia significantly increased the abundance of Bacteroidetes,which was suppressed in the gut microbiota of colitis mice.Interestingly,cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes.We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS,which might affect the gut microbiota.CONCLUSION These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota,which highlights a novel approach for the treatment of IBD.展开更多
The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus re...The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.展开更多
AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-b...AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.展开更多
Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a se...Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.展开更多
In some species of growing mammals glutamine is an essential amino acid that,if inadequate in the diet,is needed for normal growth and development.It is thus sometimes considered to be a conditionally essential amino ...In some species of growing mammals glutamine is an essential amino acid that,if inadequate in the diet,is needed for normal growth and development.It is thus sometimes considered to be a conditionally essential amino acid in some species.A review of studies that have measured L-glutamine concentrations([glutamine])in horses demonstrates that plasma[glutamine]has routinely been reported to be much lower(~330μmol/L)than in other mammals(>600μmol/L).Plasma[glutamine]represents the balance between intestinal transport into the blood after hepatic first pass,tissue synthesis and cellular extraction.The hypothesis is proposed that sustained low plasma[glutamine]represents a chronic state of sub-optimal glutamine intake and glutamine synthesis that does not meet the requirements for optimum health.While this may be without serious consequence in feral and sedentary horses,there is evidence that provision of supplemental dietary glutamine ameliorates a number of health consequences,particularly in horses with elevated metabolic demands.The present review provides evidence that glutamine is very important(and perhaps essential)for intestinal epithelial cells in mammals including horses,that horses with low plasma[glutamine]represents a sub-optimal state of well-being,and that horses supplemented with glutamine exhibit physiological and health benefits.展开更多
OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer(Lti)cells,a subset of group 3 innate lymphoid cells(ILC3s).OX40L expression in subsets of intestinal ILC3s and the ...OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer(Lti)cells,a subset of group 3 innate lymphoid cells(ILC3s).OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown.Here,we showed intestinal ILC3s marked as an OX40L high population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1–/–mice.All ILC3 subsets expressed OX40L,and NCR–ILC3s were the most abundant source of OX40L.The expression of OX40L in ILC3s could be upregulated during inflammation.In addition to tumor necrosis factor(TNF)-like cytokine 1A(TL1A),which has been known as a trigger for OX40L,we found that Poly(I:C)representing viral stimulus promoted OX40L expression in ILC3s via a cell-autonomous manner.Furthermore,we demonstrated that IL-7-STAT5 signaling sustained OX40L expression by ILC3s.Intestinal regulatory T cells(Tregs),most of which expressed OX40,had defective expansion in chimeric mice,in which ILC3s were specifically deficient for OX40L expression.Consistently,co-localization of Tregs and ILC3s was found in the cryptopatches of the intestine,which suggests the close interaction between ILC3s and Tregs.Our study has unveiled the crosstalk between Tregs and ILC3s in mucosal tissues through OX40–OX40L signaling,which is crucial for the homeostasis of intestinal Tregs.展开更多
Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorgani...Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases.As an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections.In turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic bacteria.As a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies.This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms.The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.展开更多
Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berb...Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.展开更多
Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function ...Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.展开更多
Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the r...Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.展开更多
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)the Science and Technology Projects of Xiamen Science and Technology Bureau(3502Z20183034)。
文摘The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.
基金supported by College Student Innovation and Entrepreneurship Training(202110069122)Tianjin Key R&D Plan-Key Projects Supported by Science and Technology(19YFZCSN00010)Tianjin Agricultural Science and Technology Achievements Transformation and Promotion Project(202101120)。
文摘Green tea and its bioactive components possess many health-promoting and disease-preventing benefits,especially anti-inflammatory,antioxidant,anticancer,and metabolic modulation effects with multi-target modes of action.In contrast,the effects and mechanisms of tea and its components on the immune system are rarely reviewed.The study aimed to review the most potent compounds in tea that affect the immune systems and mechanisms associated with it.As a result of in vitro studies,animal models,and human trials,researchers have found that green tea extracts and compounds have the possibility of modulating the innate immune system,adaptive immune system,and intestinal immune system.In immune-related diseases,tea polyphenols are the most significant compounds that modify immune functions,though other compounds are being investigated and cannot be ruled out.The review provides a new perspective on how the immune-regulatory effects of tea and its components are exerted on immune systems,as well as how they affect the emergence and treatment of diseases.
基金National Natural Science Foundation of China(31602099)Key Laboratory of Prevention and Control Agents for Animal Bacteriosis(Ministry of Agriculture)(KLPCAAB-2018-06)the Engineering Research Center of Ecology and Agricultural Use of Wetland,Ministry of Education(KF201913)。
文摘[Objectives]The aim of this study was to investigate the effects of APS-sEPS(a polysaccharide compound of Astragalus polysaccharides and sulfated Epimedium polysaccharide)on intestinal mucosal immunity and structural morphology.[Methods]Firstly,the diarrhea model was established using the optimal dose of magnesium sulfate in mice.Then,the diarrhea mice were randomly divided into three groups and given either physiological saline(diarrhea model group)or injected with APS-sEPS or APS.The normal mice were selected as a control group.After administration,the duodenum,jejunum and ileum were processed microtome section,and observed for describing the small intestine morphology,villus height and crypt depth.The tissue homogenates of the duodenum,jejunum and ileum were gathered to detect the changes of sIgA,IL-4 and IL-10.[Results]The results indicated that APS-sEPS could effectively relieve diarrhea in mice.In the APS-sEPS group,the villus heights of duodenum,jejunum and ileum were increased and the depth of crypt was reduced.The contents of IL-4,IL-10 and sIgA in jejunum and ileum in APS-sEPS group were significantly higher than that in the control group(P<0.05).[Conclusions]These results indicated that APS-sEPS promoted the recovery of intestinal morphological structure and enhanced the mucosa immunity of the small intestine.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)the National Natural Science Foundation(31872904)。
文摘With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.
基金Supported by the Zhejiang Provincial Natural Science Foundation,No.LY19H030011,No.LQ20C010005,and No.LQ19H030009Key Project of Province and Ministry Foundation,No.WKJZJ2124。
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic disease with recurrent intestinal inflammation.Although the exact etiology of IBD remains unknown,the accepted hypothesis of the pathogenesis to date is that abnormal immune responses to the gut microbiota are caused by environmental factors.The role of the gut microbiota,particularly the bidirectional interaction between the brain and gut microbiota,has gradually attracted more attention.AIM To investigate the potential effect of spinal anesthesia on dextran sodium sulfate(DSS)-induced colitis mice and to detect whether alterations in the gut microbiota would be crucial for IBD.METHODS A DSS-induced colitis mice model was established.Spinal anesthesia was administered on colitis mice in combination with the methods of cohousing and fecal microbiota transplantation(FMT)to explore the role of spinal anesthesia in IBD and identify the potential mechanisms involved.RESULTS We demonstrated that spinal anesthesia had protective effects against DSS-induced colitis by alleviating clinical symptoms,including reduced body weight loss,decreased disease activity index score,improved intestinal permeability and colonic morphology,decreased inflammatory response,and enhanced intestinal barrier functions.Moreover,spinal anesthesia significantly increased the abundance of Bacteroidetes,which was suppressed in the gut microbiota of colitis mice.Interestingly,cohousing with spinal anesthetic mice and FMT from spinal anesthetic mice can also alleviate DSS-induced colitis by upregulating the abundance of Bacteroidetes.We further showed that spinal anesthesia can reduce the increase in noradrenaline levels induced by DSS,which might affect the gut microbiota.CONCLUSION These data suggest that microbiota dysbiosis may contribute to IBD and provide evidence supporting the protective effects of spinal anesthesia on IBD by modulating the gut microbiota,which highlights a novel approach for the treatment of IBD.
基金supported by the National Key Research and Development Program of China (2018YFA0903200)the National Natural Science Foundation of China (81790633 and 30901190)+1 种基金the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2019-I2M-5-045)the Public Welfare Technology Research Program of Zhejiang Province (LGF18H310004)
文摘The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.
基金Supported by A grant from Nestec Ltd,Vevey,Switzerland
文摘AIM:To investigate whether probiotic bacteria,given perioperatively,might adhere to the colonic mucosa, reduce concentration of pathogens in stools,and modulate the local immune function. METHODS:A randomized,double-blind clinical trial was carried out in 31 subjects undergoing elective colorectal resection for cancer.Patients were allocated to receive either a placebo(group A,n=10),or a dose of 10 7 of a mixture of Bifidobacterium longum(BB536) and Lactobacillus johnsonii(La1)(group B,n=11),or the same mixture at a concentration of 10 9 (group C,n=10).Probiotics,or a placebo,were given orally 2 doses/d for 3 d before operation.The same treatment continued postoperatively from day two to day four. Stools were collected before treatment,during surgery (day 0)and 5 d after operation.During the operation, colonic mucosa samples were harvested to evaluate bacterial adherence and to assess the phenotype of dendritic cells(DCs)and lymphocyte subsets by surface antigen expression(flow cytometry).The presence of BB536 and La1 was evaluated by the random amplified polymorphism DNA method with specific polymerase chain reaction probes. RESULTS:The three groups were balanced for baseline and surgical parameters.BB536 was never found at any time-points studied.At day 0,La1 was present in 6/10(60%)patients in either stools or by biopsy in group C,in 3/11(27.2%)in group B,and none in the placebo group(P=0.02,C vs A).There was a linear correlation between dose given and number of adher- ent La1(P=0.01).The rate of mucosal colonization by enterobacteriacae was 30%(3/10)in C,81.8%(9/11) in B and 70%(7/10)in A(P=0.03,C vs B).The Enterobacteriacae count in stools was 2.4(log10 scale) in C,4.6 in B,and 4.5 in A(P=0.07,C vs A and B). The same trend was observed for colonizing enterococ- ci.La1 was not found at day+5.We observed greater expression of CD3,CD4,CD8,and naive and memory lymphocyte subsets in group C than in group A with a dose response trend(C>B>A).Treatment didnot affect DC phenotype or activation,but after ex vivo stimulation with lipopolysaccharides,groups C and B had a lower proliferation rate compared to group A (P=0.04).Moreover,dendritic phenotypes CD83-123, CD83-HLADR,and CD83-11c(markers of activation) were significantly less expressed in patients colonized with La1(P=0.03 vs not colonized). CONCLUSION:La1,but not BB536,adheres to the colonic mucosa,and affects intestinal microbiota byreducing the concentration of pathogens and modulates local immunity.
基金supported by the grants from the Sichuan Science and Technology Program,China(No.2023NSFSC0614,2022YFS0624)grant from Science and Technology Program of Luzhou,China(No.21CGZHPT0001,2022-YJY-127)+1 种基金grant from Southwest Medical University,China(No.2021ZKZD017)grant from The Open Research Project Program of the State Key Laboratory of Quality Research in Chinese Medicine(University of Macao),China(SKL-QRCM-OP21006).
文摘Ulcerative colitis(UC)is one of types of inflammatory bowel disease with high recurrence.Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC.Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC.Many Chinese herbal medicines including some of single herb,herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity.Some clinical trials have shown promising results.This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity.The existing clinical trials are also summarized.
文摘In some species of growing mammals glutamine is an essential amino acid that,if inadequate in the diet,is needed for normal growth and development.It is thus sometimes considered to be a conditionally essential amino acid in some species.A review of studies that have measured L-glutamine concentrations([glutamine])in horses demonstrates that plasma[glutamine]has routinely been reported to be much lower(~330μmol/L)than in other mammals(>600μmol/L).Plasma[glutamine]represents the balance between intestinal transport into the blood after hepatic first pass,tissue synthesis and cellular extraction.The hypothesis is proposed that sustained low plasma[glutamine]represents a chronic state of sub-optimal glutamine intake and glutamine synthesis that does not meet the requirements for optimum health.While this may be without serious consequence in feral and sedentary horses,there is evidence that provision of supplemental dietary glutamine ameliorates a number of health consequences,particularly in horses with elevated metabolic demands.The present review provides evidence that glutamine is very important(and perhaps essential)for intestinal epithelial cells in mammals including horses,that horses with low plasma[glutamine]represents a sub-optimal state of well-being,and that horses supplemented with glutamine exhibit physiological and health benefits.
基金This study was supported by grants 2015CB943400 and 2014CB943300 from the Ministry of Science and Technology of Chinagrant XDB19000000 from the“Strategic priority research program of the Chinese Academy of Sciences”+1 种基金grants 91542102 and 31570887 from the National Natural Science Foundation of ChinaChina's Youth 1000 Talent Program to Q.J.
文摘OX40L is one of the co-stimulatory molecules that can be expressed by splenic lymphoid tissue inducer(Lti)cells,a subset of group 3 innate lymphoid cells(ILC3s).OX40L expression in subsets of intestinal ILC3s and the molecular regulation of OX40L expression in ILC3s are unknown.Here,we showed intestinal ILC3s marked as an OX40L high population among all the intestinal leukocytes and were the dominant source of OX40L in Rag1–/–mice.All ILC3 subsets expressed OX40L,and NCR–ILC3s were the most abundant source of OX40L.The expression of OX40L in ILC3s could be upregulated during inflammation.In addition to tumor necrosis factor(TNF)-like cytokine 1A(TL1A),which has been known as a trigger for OX40L,we found that Poly(I:C)representing viral stimulus promoted OX40L expression in ILC3s via a cell-autonomous manner.Furthermore,we demonstrated that IL-7-STAT5 signaling sustained OX40L expression by ILC3s.Intestinal regulatory T cells(Tregs),most of which expressed OX40,had defective expansion in chimeric mice,in which ILC3s were specifically deficient for OX40L expression.Consistently,co-localization of Tregs and ILC3s was found in the cryptopatches of the intestine,which suggests the close interaction between ILC3s and Tregs.Our study has unveiled the crosstalk between Tregs and ILC3s in mucosal tissues through OX40–OX40L signaling,which is crucial for the homeostasis of intestinal Tregs.
基金supported by the National Natural Science Foundation of China(81873098 and 81770434)the National Key Research and Development Program of China(2018YFC2000504).
文摘Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens(including bacteria,viruses,fungi,protozoa,or parasites)or their toxic products.A large number of microorganisms colonize the intestinal tract of healthy people,which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases.As an“invisible organ,”the intestinal flora is closely related to human nutrition metabolism and intestinal infections.A variety of intestinal flora participates in the nutritional metabolism of amino acids,and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections.In turn,amino acids can also regulate the composition of the intestinal flora,maintain the steady-state of the intestinal flora,protect the intestinal barrier,and inhibit colonization by pathogenic bacteria.As a model animal with a clear microbial background,germ-free(GF)animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies.This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms.The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.
基金supported by the National Natural Science Foundation of China(grant numbers 81874348,81303239)the Natural Science Foundation of Anhui Province(grant numbers 1908085J29)+3 种基金the Key Research and Development Plan of Anhui Province(grant number 201904b11020023)the Open Project of State Key Laboratory of Natural Medicines(grant number SKLNMKF202007)the Provincial Foundation for Excellent Young Talents of Colleges and Universities of Anhui Province(grant number gxyqZD2018052)the Anhui Provincial Department of Education(grant number KJ2018A0282)。
文摘Objective:To investigate the dynamic regulation of self-assembled aggregations(SAA)in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying.Methods:The effects of SAA on berberine(Ber)absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer’s patches(PPs).The expression levels of ZO-1,Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction(TJ)between intestinal epithelium cells.The expression levels of T-box-containing protein expressed in T cells,signal transducers and activators of tranion-6,retinoic acid receptor-related orphan receptor ct and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-c(IFN-c),interleukin-4(IL-4),interleukin-17(IL-17)and transforming growth factor-b(TGF-b)in PPs were evaluated by immunohistochemistry,to reflect the differentiation of T lymphocyte in PPs to helper T(Th)cell 1,Th2,Th17 and regulatory T(Treg)cell.To confirm the correlation between SAA in Coptidis Rhizoma decoction,PPs-associated immunity and intestinal epithelium permeability,SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression.Results:SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment,with the participation of PPs.The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs.The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation,inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression.Conclusion:SAA can improve the Ber absorption in small intestine,through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression.These findings might enlighten the research of traditional Chinese medicine decoction.
文摘Insects live in incredibly complex environments.The intestinal epithelium of insects is in constant contact with microorganisms,some of which are beneficial and some harmful to the host.Insect gut health and function are maintained through multidimensional mechanisms that can proficiently remove foreign pathogenic microorganisms while effectively maintaining local symbiotic microbial homeostasis.The basic immune mechanisms of the insect gut,such as the dual oxidase-reactive oxygen species(Duox-ROS)system and the immune deficiency(Imd)-signaling pathway,are involved in the maintenance of microbial homeostasis.This paper reviews the role of physical defenses,the Duox-ROS and Imd signaling pathways,the Janus kinase/signal transducers and activators of transcription signaling pathway,and intestinal symbiotic flora in the homeostatic maintenance of the insect gut microbiome.
基金supported by the grants from the National Key R&D Program of China(No.2020YFA0509200)the National Natural Science Foundation of China(Nos.82002622,81830081,31970718,and 81972203)+1 种基金the Shanghai Municipal Health Commission,Collaborative Innovation Cluster Project(No.2019CXJQ02)the Youth Project of Shanghai Municipal Health Commission(No.20194Y0096)
文摘Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.
