Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant f...Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.展开更多
AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly dist...AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.展开更多
AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into thre...AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into three groups： normal control （NC） group, partially hepatectomized （PH） group and a sham-operated （SO） group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation （ 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h）. NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin （ET） and diamine oxidase （DAO） levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells （KCs） in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS： Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation （r = 0.757, P 〈 0.05） between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum （La） particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION： The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,展开更多
Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal...Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.展开更多
Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Intestinal defense system includi...Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Intestinal defense system including microbial barrier, immunologic barrier, mechanical barrier, chemical barrier, plays an important role in the maintenance of intestinal function. Under normal circumstances, the intestinal barrier can prevent intestinal bacteria through the intestinal wall from spreading to the body. Severe infection, trauma, shock, cirrhosis, malnutrition, immune suppression conditions, intestinal bacteria and endotoxin translocation, can lead to multiple organ dysfunction. The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. In patients with cirrhosis, primary and intestinal flora imbalance, intestinal bacterial overgrowth, intestinal mucosal barrier dysfunction, endotoxemia is associated with weakened immunity.展开更多
Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role...Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role in reducing inflammation.In addition,the gut has long been hypothesized to be the“motor”of critical illness,driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation.展开更多
Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this stud...Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels ...A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.展开更多
INTRODUCTION Previous clinical and experimental studies haveindicated that an early endotoxemia occurred after amajor burn.It is unlikely that burn wound sepsis isthe source of circulating endotoxin in less than 12hou...INTRODUCTION Previous clinical and experimental studies haveindicated that an early endotoxemia occurred after amajor burn.It is unlikely that burn wound sepsis isthe source of circulating endotoxin in less than 12hour after burn.Increasing evidence demonstratesthat the bacteria and endotoxin in thegastrointestinal tract can pass through the gutbarrier into blood circulation to form enterogenicendotoxemia following burn.However。展开更多
文摘Diabetes mellitus(DM)is a complicated,globally expanding disease that is influenced by hereditary and environmental variables.Changes in modern society’s food choices,physical inactivity,and obesity are significant factors in the development of type 2 DM(T2DM).The association between changes in intestinal flora and numerous disorders,including obesity,diabetes,and cardiovascular diseases,has been studied in recent years.The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients’intestinal flora,as well as their therapeutic choices.Also included is a summary of the antidiabetic benefits of natural compounds demonstrated by studies.The short-chain fatty acids theory,the bile acid theory,and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM.Due to an intestinal flora imbalance,abnormalities in shortchain fatty acids and secondary bile acids have been found in diabetic patients.Additionally,metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation.The agenda for diabetes treatment includes the use of short-chain fatty acids,probiotics,prebiotics in the diet,fecal bacteria transplantation,and antibiotics.Animal studies have proven the antidiabetic benefits of numerous bioactive substances,including Flavonoids,Alkaloids,Saponin,and Allicin.However,further research is required to contribute to the treatment of diabetes.
基金Supported by Beijing Municipal Science & Technology Commission Major Scitech Program,No.H020920050130
文摘AIM： To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotoxemia and to elucidate the potential mechanism of this dysfunction. METHODS： Male Wistar rats were randomly distributed into two groups： control group and lipopolysaccharide （LPS） group. Endotoxemia was induced by a single caudal venous injection of LPS. Animals were sacrificed in batches 2, 6, 12 and 24 h after LPS infusion. The number of microfold （M）-cells, dendritic cells （DCs）, CD4＋ T cells, CD8＋ T cells, regulatory T （Tr） cells and IgA＋ B cells in the intestinal mucosa were counted after immunohistochemical staining. Apoptotic lymphocytes were counted after TUNEL staining. The levels of interleukin （IL）-4, interferon （IFN）-γ, and forkhead box P3 （Foxp3） in mucosal homogenates were measured by ELISA. The secretory IgA （sIgA） content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS： This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury. The number of M-cells, DCs, CD8~ T cells, and IgA~ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased significantly. The number of CD4＋ T cells increased in the early stages and then slightly decreased by 24 h. The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period. The level of IFN-T increased slightly in the early stages and then decreased markedly by the 24 h time point. Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION： Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia. The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunode- ficiency.
基金a grant from the fund for key scientific and technical programs of Shanxi, No. 051094-9,Shanxi Province,China
文摘AIM： To explore the mechanism of intestinal endotoxemia （IETM） formation and its changes in partially hepatectomized （PH） rats. METHODS： One-hundred and two adult male Wistar rats were randomly divided into three groups： normal control （NC） group, partially hepatectomized （PH） group and a sham-operated （SO） group. To study the dynamic changes, rats were sacrificed before and at different time points after partial hepatectomy or the sham-operation （ 6 h, 12 h, 24 h, 36 h, 48 h, 72 h, 120 h and 168 h）. NC group was used as Oh time point in observation, namely 0 h group. For each time point indicated, six rats were used in parallel. Endotoxin （ET） and diamine oxidase （DAO） levels were determined in serum using Limulus Lysate test with chromogenic substrate and spectrophotometry. Intestinal mucosa barrier was observed under opticcal or electron microscope. The number and functional state of Kupffer cells （KCs） in the remnant regenerating liver were measured by immunohistochemical staining. RESULTS： Serum ET levels significantly increased during 6-72 h period after PH compared with NC and SO groups, and there were two peak values at 12 and 48 h while serum DAO level significantly increased at 12 and 24 h. There was positive correlation （r = 0.757, P 〈 0.05） between the levels of DAO and ET dynamic changes. The optical examination showed neutrophil margination and superficial necrosis of the villi in the intestinal mucosa during 6-24 h period after PH. The penetrated electron microscope examination showed thatthe gaps between intestinal mucosa cells were increased and the Lanthanum （La） particles were observed among the intestinal mucosa cells during 6-48 h period, The numbers of KCs in the remnant regenerating liver were significantly increased during 24-168 h period after PH, However, the activation of KCs was predominantly observed at 48 h after PH. CONCLUSION： The mechanism of IETM in PH rats might be the injury of intestinal mucosa barrier and the decrease of the absolute number of KCs as well as the depression of functional state of KCs, This observation is of potential value in patients undergoing liver resection,
文摘Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.
文摘Intestinal barrier dysfunction, facilitating translocation of bacteria and bacterial products, plays an important role in the pathophysiology of liver cirrhosis and its complications. Intestinal defense system including microbial barrier, immunologic barrier, mechanical barrier, chemical barrier, plays an important role in the maintenance of intestinal function. Under normal circumstances, the intestinal barrier can prevent intestinal bacteria through the intestinal wall from spreading to the body. Severe infection, trauma, shock, cirrhosis, malnutrition, immune suppression conditions, intestinal bacteria and endotoxin translocation, can lead to multiple organ dysfunction. The intestinal microflora is not only involved in the digestion of nutrients, but also in local immunity, forming a barrier against pathogenic microorganisms. The derangement of the gut microflora may lead to microbial translocation, defined as the passage of viable microorganisms or bacterial products from the intestinal lumen to the mesenteric lymph nodes and other extraintestinal sites. In patients with cirrhosis, primary and intestinal flora imbalance, intestinal bacterial overgrowth, intestinal mucosal barrier dysfunction, endotoxemia is associated with weakened immunity.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81873434)and the Natural Science Foundation of Hubei Province(No.2020CFA065).
文摘Objective:The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy,which is a strong predictor of mortality in patients with severe sepsis.Simvastatin plays an important role in reducing inflammation.In addition,the gut has long been hypothesized to be the“motor”of critical illness,driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation.
基金This work was supported in part by grants from the National Key Program for Fundamental Research and Development(Grant No.G1999054203)the National Natural Science Outstanding Youth Foundation of China(Grant No.30125020).
文摘Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
文摘A "leaky gut" may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin,activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis.
基金the National Natural Science Foundation of China,No.39290700.
文摘INTRODUCTION Previous clinical and experimental studies haveindicated that an early endotoxemia occurred after amajor burn.It is unlikely that burn wound sepsis isthe source of circulating endotoxin in less than 12hour after burn.Increasing evidence demonstratesthat the bacteria and endotoxin in thegastrointestinal tract can pass through the gutbarrier into blood circulation to form enterogenicendotoxemia following burn.However。
