Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health a...Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.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
The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in de...The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn's ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thin- ner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn's ileitis and UC may enablethe luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.展开更多
AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with...AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract.METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed.RESULTS: The two groups featured similar demographic and clinical data. Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers. Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases. No deaths were reported following infections. CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions.展开更多
基金This study was supported by grants from the National Basic Research Program of China （973 Program, 2013CB531401）, the Major Science and Technology Program of Zhejiang Province （2014C03039）, and the Natural Science Foundation of Zhejiang Province （R16H260001）. We acknowledge Doctors Chunlei Chen, Bo Li, Jing Guo, Ding Shi, Qiongling Bao, Silan Gu, Yanfei Chen, Kai Zhou, Qixiang Luo, Ruiqi Tang, and Xiangyang Jiang for the literature search and the preparation for the manuscript. We also thank the reviewers for their thoughtful and helpful comments.
文摘Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.
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 Robert Bosch Foundation Stuttgart Germany and the Emmy Noether program (Wehkamp J) of the Deutsche Forschungsgemeinschaft (DFG)
文摘The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn's ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thin- ner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn's ileitis and UC may enablethe luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system.
文摘AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract.METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed.RESULTS: The two groups featured similar demographic and clinical data. Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers. Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases. No deaths were reported following infections. CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions.
