The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and ...The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.展开更多
Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic...Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.展开更多
The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver ho...The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.展开更多
To evaluate the risk of transmission of carbapenem-resistant Enterobacteriaceae(CRE) and their related superbugs during gastrointestinal(GI) endoscopy. Reports of outbreaks linked to GI endoscopes contami-nated with d...To evaluate the risk of transmission of carbapenem-resistant Enterobacteriaceae(CRE) and their related superbugs during gastrointestinal(GI) endoscopy. Reports of outbreaks linked to GI endoscopes contami-nated with different types of infectious agents, includ-ing CRE and their related superbugs, were reviewed. Published during the past 30 years, both prior to and since CRE's emergence, these reports were obtained by searching the peer-reviewed medical literature(via the United States National Library of Medicine's "MEDLINE" database); the Food and Drug Administration's Manu-facturer and User Facility Device Experience database, or "MAUDE"; and the Internet(via Google's search engine). This review focused on an outbreak of CRE in 2013 following the GI endoscopic procedure known as endoscopic retrograde cholangiopancreatography, or ERCP, performed at "Hospital X" located in the sub-urbs of Chicago(IL; United States). Part of the largest outbreak of CRE in United States history, the infection and colonization of 10 and 28 of this hospital's patients, respectively, received considerable media attention and was also investigated by the Centers for Disease Con-trol and Prevention(CDC), which published a report about this outbreak in Morbidity and Mortality WeeklyReport(MMWR), in 2014. This report, along with the results of an independent inspection of Hospital X's in-fection control practices following this CRE outbreak, were also reviewed. While this article focuses primar-ily on the prevention of transmissions of CRE and their related superbugs in the GI endoscopic setting, some of its discussion and recommendations may also apply to other healthcare settings, to other types of flexible endoscopes, and to other types of transmissible infec-tious agents. This review found that GI endoscopy is an important risk factor for the transmission of CRE and their related superbugs, having been recently as-sociated with patient morbidity and mortality following ERCP. The CDC reported in MMWR that the type of GI endoscope, know展开更多
Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosi...Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis.Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis.The increasing knowledge of structural,immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades.Therefore,early identification of patients at the highest risk for developing infections and infectionrelated complications is required to tailor the currently available measures of surveillance,prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis.展开更多
基金Supported by(in part)FARB-ex 60%2012 of the University of Salerno grant to Vajro P
文摘The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy.
文摘Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.
文摘The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.
基金Supported by An educational grant provided by FUJIFILM Medical Systems,USA,Inc.,Endoscopy Division(Wayne,NJUnited States)
文摘To evaluate the risk of transmission of carbapenem-resistant Enterobacteriaceae(CRE) and their related superbugs during gastrointestinal(GI) endoscopy. Reports of outbreaks linked to GI endoscopes contami-nated with different types of infectious agents, includ-ing CRE and their related superbugs, were reviewed. Published during the past 30 years, both prior to and since CRE's emergence, these reports were obtained by searching the peer-reviewed medical literature(via the United States National Library of Medicine's "MEDLINE" database); the Food and Drug Administration's Manu-facturer and User Facility Device Experience database, or "MAUDE"; and the Internet(via Google's search engine). This review focused on an outbreak of CRE in 2013 following the GI endoscopic procedure known as endoscopic retrograde cholangiopancreatography, or ERCP, performed at "Hospital X" located in the sub-urbs of Chicago(IL; United States). Part of the largest outbreak of CRE in United States history, the infection and colonization of 10 and 28 of this hospital's patients, respectively, received considerable media attention and was also investigated by the Centers for Disease Con-trol and Prevention(CDC), which published a report about this outbreak in Morbidity and Mortality WeeklyReport(MMWR), in 2014. This report, along with the results of an independent inspection of Hospital X's in-fection control practices following this CRE outbreak, were also reviewed. While this article focuses primar-ily on the prevention of transmissions of CRE and their related superbugs in the GI endoscopic setting, some of its discussion and recommendations may also apply to other healthcare settings, to other types of flexible endoscopes, and to other types of transmissible infec-tious agents. This review found that GI endoscopy is an important risk factor for the transmission of CRE and their related superbugs, having been recently as-sociated with patient morbidity and mortality following ERCP. The CDC reported in MMWR that the type of GI endoscope, know
基金Supported by The Federal Ministry of Education and Research(BMBF)Germany(FKZ:01 E0 1002)to Bruns T
文摘Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis.Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis.The increasing knowledge of structural,immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades.Therefore,early identification of patients at the highest risk for developing infections and infectionrelated complications is required to tailor the currently available measures of surveillance,prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis.
