The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established ...The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established as well as potential pathogens. Furthermore, it influences the motility and perfusion of the intestinal wall, stimu- lates the intestinal immune system and therefore also the so-called common mucosal immune system, reducing bacterial translocation and producing vitamins. Immune homeostasis at mucosal level results from a controlled response to intestinal luminal antigens. In liver cirrhosis, there are many changes in its function, mostly an increase in bacterial overgrowth and translocation. In this review, probiotics and their indications in hepatology are generally discussed. According to recent knowledge, these preparations are indicated in clinical practice only for cases of hepatic encephalopathy. Probiotics are able to decrease the permeability of the intestinal wall, and decrease bacterial translocation and endotoxemia in animal models as well as in clinical studies, which is extremely important in the prevention of complications of liver cirrhosis and infection after liver transplantation. Probiotics could limit oxidative and inflammatory liver damage and, in some situations, improve the histological state, and thus non-alcoholic steatohepatitis could be considered as another possible indication.展开更多
Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy...Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.展开更多
Inflammasomes and their product interleukin 18(IL-18)play important roles in gut microbiota monitoring and homeostasis,and their loss of function could lead to microbiota dysbiosis and accelerate disease progression.H...Inflammasomes and their product interleukin 18(IL-18)play important roles in gut microbiota monitoring and homeostasis,and their loss of function could lead to microbiota dysbiosis and accelerate disease progression.However,the impacts of the resulting microbiota dysbiosis on the mucosal immune system are largely unknown.Here,we show that dysbiotic microbiota from Il18^(-/-)mice induced immune cell loss in the small intestine(SI)in an inflammasome-independent manner.Cohousing experiments revealed that the immunotoxic phenotype of these microbiota was transferable to wild type(WT)mice and induced immune cell death through the receptor-interacting protein kinase 3(RIP3)-mixed lineage kinase domain like pseudokinase(MLKL)pathway.Analysis of microbiota composition identified two types of bacteria at the genus level,Ureaplasma and Parasutterella,that accumulated in Il18^(-/-)mice and negatively mediated changes in immune cells in the SI.Furthermore,dysbiosis in Il18^(-/-)mice also contributed to increased susceptibility to Listeria infection.Collectively,our results demonstrate that IL-18 is essential to microbiota homeostasis and that dysbiotic microbiota could significantly shape the landscape of the immune system.展开更多
文摘The paper provides a basic review of intestinal microflora and its importance in liver diseases. The intestinal microflora has many important functions, above all to maintain the microbial barrier against established as well as potential pathogens. Furthermore, it influences the motility and perfusion of the intestinal wall, stimu- lates the intestinal immune system and therefore also the so-called common mucosal immune system, reducing bacterial translocation and producing vitamins. Immune homeostasis at mucosal level results from a controlled response to intestinal luminal antigens. In liver cirrhosis, there are many changes in its function, mostly an increase in bacterial overgrowth and translocation. In this review, probiotics and their indications in hepatology are generally discussed. According to recent knowledge, these preparations are indicated in clinical practice only for cases of hepatic encephalopathy. Probiotics are able to decrease the permeability of the intestinal wall, and decrease bacterial translocation and endotoxemia in animal models as well as in clinical studies, which is extremely important in the prevention of complications of liver cirrhosis and infection after liver transplantation. Probiotics could limit oxidative and inflammatory liver damage and, in some situations, improve the histological state, and thus non-alcoholic steatohepatitis could be considered as another possible indication.
文摘Inflammatory bowel disease （IBD） arises from disruption of immune tolerance to the gut commensal microbiota, leading to chronic intestinal inflammation and mucosal damage in genetically predisposed hosts. In healthy individuals the intestinal microbiota have a symbiotic relationship with the host organism and possess important and unique functions, including a metabolic function （i.e. digestion of dietary compounds and xenobiotics, fermentation of undigestible carbohydrates with production of short chain fatty acids）, a mucosal barrier function （i.e. by inhibiting pathogen invasion and strengthening epithelial barrier integrity）, and an immune modula- tory function （i.e. mucosal immune system priming and maintenance of intestinal epithelium homeostasis）. A fine balance regulates the mechanism that allows co- existence of mammals with their commensal bacteria. In IBD this mechanism of immune tolerance is impaired because of several potential causative factors. The gut microbiota composition and activity of IBD patients are abnormal, with a decreased prevalence of dominant members of the human commensal microbiota （i.e. Clostridium IXa and IV groups, Bacteroides, bifldobacteria） and a concomitant increase in detrimental bacteria （i.e. sulphate-reducing bacteria, Escherichia coll. The observed dysbiosis is concomitant with defectiveinnate immunity and bacterial killing （i.e. reduced mucosal defensins and IgA, malfunctioning phagocytosis） and overaggressive adaptive immune response （due to ineffective regulatory T cells and antigen presenting cells）, which are considered the basis of IBD pathogen- esis. However, we still do not know how the interplay between these parameters causes the disease. Studies looking at gut microbial composition, epithelial integrity and mucosal immune markers in genotyped IBD populations are therefore warranted to shed light on this obscure pathogenesis.
基金supported by the National Key Research and Development Program of China(2020YFA0509101)the National Natural Science Foundation of China(91742202,81722022,and 81821001)the Young Talent Support Program and Fundamental Research Funds for the Central Universities and the University Synergy Innovation Program of Anhui Province(GXXT-2019-026)。
文摘Inflammasomes and their product interleukin 18(IL-18)play important roles in gut microbiota monitoring and homeostasis,and their loss of function could lead to microbiota dysbiosis and accelerate disease progression.However,the impacts of the resulting microbiota dysbiosis on the mucosal immune system are largely unknown.Here,we show that dysbiotic microbiota from Il18^(-/-)mice induced immune cell loss in the small intestine(SI)in an inflammasome-independent manner.Cohousing experiments revealed that the immunotoxic phenotype of these microbiota was transferable to wild type(WT)mice and induced immune cell death through the receptor-interacting protein kinase 3(RIP3)-mixed lineage kinase domain like pseudokinase(MLKL)pathway.Analysis of microbiota composition identified two types of bacteria at the genus level,Ureaplasma and Parasutterella,that accumulated in Il18^(-/-)mice and negatively mediated changes in immune cells in the SI.Furthermore,dysbiosis in Il18^(-/-)mice also contributed to increased susceptibility to Listeria infection.Collectively,our results demonstrate that IL-18 is essential to microbiota homeostasis and that dysbiotic microbiota could significantly shape the landscape of the immune system.
