Adult ; Female ; Gases ; Humans ; Intestine, Small ; metabolism ; microbiology ; physiology ; Liver Cirrhosis ; metabolism ; microbiology ; Male ; Middle Aged

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.
Antigens, CD14/metabolism ; Bacterial Translocation ; Gastrointestinal Tract/*microbiology ; Humans ; Hypertension, Portal/metabolism/*pathology ; Liver/metabolism/*microbiology ; Liver Cirrhosis/metabolism/*pathology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Toll-Like Receptors/metabolism

OBJECTIVESTo investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism.

METHODSSpecific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin, intestinal bacterial count, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied.

RESULTSIschemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in I/R group compared to those in the sham group. Intestinal Bifidobacterium and Lactobacillus decreased and intestinal Enterobacteria and Enterococci, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.

CONCLUSIONI/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function, which contributes to endotoxemia and bacterial translocation to kidney.

Animals ; Bacterial Translocation ; Endotoxins ; blood ; Intestinal Mucosa ; microbiology ; Intestine, Small ; microbiology ; Liver ; blood supply ; injuries ; metabolism ; microbiology ; Male ; Malondialdehyde ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; metabolism ; microbiology ; Superoxide Dismutase ; metabolism

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver dysfunction and a significant global health problem with substantial rise in prevalence over the last decades. It is becoming increasingly clear that NALFD is not only predominantly a hepatic manifestation of metabolic syndrome, but also involves extra-hepatic organs and regulatory pathways. Therapeutic options are limited for the treatment of NAFLD. Accordingly, a better understanding of the pathogenesis of NAFLD is critical for gaining new insight into the regulatory network of NAFLD and for identifying new targets for the prevention and treatment of NAFLD. In this review, we emphasize on the current understanding of the inter-organ crosstalk between the liver and peripheral organs that contributing to the pathogenesis of NAFLD.
Adipose Tissue ; pathology ; Animals ; Extracellular Vesicles ; metabolism ; Humans ; Hypothalamus ; metabolism ; Intestines ; microbiology ; pathology ; Non-alcoholic Fatty Liver Disease ; etiology ; metabolism ; microbiology ; pathology

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.
Animals ; Bile Acids and Salts ; metabolism ; Choline ; metabolism ; Dietary Supplements ; Energy Metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Intestines ; microbiology ; Non-alcoholic Fatty Liver Disease ; microbiology ; therapy

Despite septic arthritis is increasingly being reported in elderly patients with diabetes or alcoholism, reported cases of spontaneous bacterial arthritis in cirrhotic patients are extremely rare. We present the first reported case of K. pneumoniae septic arthritis and spontaneous bacterial peritonitis in a cirrhotic patient with hepatocellular carcinoma. K. pneumoniae, one of the most common causative organisms of spontaneous bacterial peritonitis in cirrhotic patients, was isolated from both the blood and the joint fluid, which suggests that the route of infection was hematogenous. After the treatment with cefotaxime and closed tube drainage, the condition of the patient was improved, and subsequently, the joint fluid became sterile and the blood cultures were proved negative. Therefore, this case provides further evidence for the mode of infection being bacteremia in cirrhotic patients and suggests that the enteric bacteremia in cirrhotics may cause infection in different organ systems.
Aged ; Animals ; Arthritis, Infectious/blood/*diagnosis/*microbiology ; *Carcinoma, Hepatocellular/pathology ; Fatal Outcome ; Female ; Humans ; Joints/chemistry/microbiology ; Klebsiella pneumoniae/*metabolism ; Liver Cirrhosis/*microbiology ; *Liver Neoplasms/pathology ; *Peritonitis/blood/microbiology/physiopathology

Brain and the gastrointestinal (GI) tract are intimately connected to form a bidirectional neurohumoral communication system. The communication between gut and brain, knows as the gut-brain axis, is so well established that the functional status of gut is always related to the condition of brain. The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract. However, recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes. These recent findings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis. To elucidate the role of gut microbiota in the gut-brain axis, precise identification of the composition of microbes constituting gut microbiota is an essential step. However, identification of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the difficulties in culture of gut microbes. Current methods for identification of microbes constituting gut microbiota are dependent on omics analysis methods by using advanced high tech equipment. Here, we review the association of gut microbiota with the gut-brain axis, including the pros and cons of the current high throughput methods for identification of microbes constituting gut microbiota to elucidate the role of gut microbiota in the gut-brain axis.
Brain ; metabolism ; Central Nervous System ; metabolism ; Gastrointestinal Tract ; metabolism ; microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Liver ; metabolism ; Metabolic Diseases ; metabolism ; pathology ; Metagenome ; Receptors, G-Protein-Coupled ; metabolism

OBJECTIVETo investigate if glutamine (Gln) reduces intestinal bacterial translocation in acute hepatic failure (AHF) in rats and its mechanisms.

METHODSAcute hepatic failure model in rat was established by intraperitoneal injection of galatosamine. The rats were randomly divided into 4 groups: the normal control group (A), prevention and treatment group (B), treatment group (C), and model group (D). The rats in groups A and D were fed with normal saline. Two days before intraperitoneal injection, the rats in group B were fed with Gln and those in group C were fed with Gln 24 hours after injection. After 4 days of treatment, the rats were sacrificed and pathological scores of liver were assessed. The percentage of intestinal bacterial transloaction and bacteria in mesenteric lymph nodes (MLN) were measured. The villus height, crypt depth of ileum mucosa were analyzed. The levels of serum diamine oxidase (DAO) were measured.

RESULTSThe liver pathological scores of groups B and C were significantly lower than those of group D. The frequency of the bacteria found in MLN was significantly lower in group B compared with group D. The levels of DAO in blood were significantly lower in groups B and C than that of group D, and the level was significantly lower in group B than in group C. The villus height and crypt depth of the mucosa were significantly greater in group B and group C than in group D, and greater in group B than in group C.

CONCLUSIONThe results of the present study show that Gln can reduce the occurrence of the intestinal bacterial translocation in AHF in rats by improving the function of intestinal barrier.

Animals ; Bacterial Physiological Phenomena ; Bacterial Translocation ; Glutamine ; metabolism ; Intestines ; metabolism ; microbiology ; Liver Failure, Acute ; complications ; microbiology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Alcoholic liver disease is a leading cause of morbidity and liver-related death worldwide. Intestinal bacterial overgrowth and dysbiosis induced by ethanol ingestion play an important role in the pathogenesis of alcoholic liver disease. After exposure to alcohol in the lumen, enteric bacteria alter their metabolism and thereby disturb intestinal homeostasis. Disruption of the mucosal barrier results in the translocation of microbial products that contribute to liver disease by inducing hepatic inflammation. In this review, we will discuss the effects of alcohol on the intestinal microbiome, and in particular, its effects on bacterial metabolism, bacterial translocation and ecological balance. A better understanding of the interactions among alcohol, the host and the microbiome will reveal new targets for therapy and lead to new treatments.
Bacterial Translocation/physiology ; Central Nervous System Depressants/metabolism ; Ethanol/metabolism ; Humans ; Intestines/*microbiology ; Lipopolysaccharides/physiology ; Liver Diseases, Alcoholic/*microbiology ; Microbiota/*physiology ; Permeability

OBJECTIVETo investigate the effects of lactulose on intestinal bacterial overgrowth (IBO), bacterial translocation (BT), intestinal transit and permeability in cirrhotic rats.

METHODSBT in all animals was assessed by bacterial culture of mesenteric lymph node (MLN), liver and spleen, and IBO was assessed by a jejunal bacterial count of the specific organism. Intestinal permeability was determined by the 24-hour urinary (99m)Tc-diethylenetriamine pentaacetatic acid ((99m)Tc-DTPA) excretion, and intestinal transit was determined by measuring the distribution of (51)Cr in the intestine.

RESULTSBT and IBO were found in 48% and 80% of the cirrhotic rats, respectively, while not in the control rats. Cirrhotic rats with IBO had significantly higher levels of intestinal endotoxin higher rates of bacterial translocation, shorter intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT were closely associated with IBO and injury of the intestinal barrier. Compared with the placebo group, lactulose-treated rats had lower rates of BT and IBO, which were closely associated with increased intestinal transit and improved intestinal permeability by lactulose.

CONCLUSIONSOur study indicate that endotoxin and bacterial translocation in cirrhotic rats may attribute to IBO and increased intestinal permeability. Lactulose that accelerates intestinal transit and improves intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.

Animals ; Bacterial Translocation ; drug effects ; Endotoxins ; analysis ; Gastrointestinal Agents ; pharmacology ; Intestines ; metabolism ; microbiology ; Lactulose ; pharmacology ; Liver Cirrhosis, Experimental ; metabolism ; microbiology ; Male ; Rats ; Rats, Sprague-Dawley