Gut microbiota and Toll-like receptors set the stage for cytokine-mediated failure of antibacterial responses in the fibrotic liver

The gut–liver axis is increasingly recognised as a key contributor to chronic liver disease. A failing gut barrier contributes to increased bacterial translocation, which results in an elevated risk of bacterial infection and a chronic inflammatory state that may promote the progression of chronic liver disease and the development of long-term complications such as fibrosis and HCC.1 2 The most important clinical consequence of increased translocation is acute bacterial infection, a common cause of hospital admissions and a major contributor to morbidity and mortality in patients with cirrhosis. Moreover, bacterial infections can lead to acute decompensation, often triggering acute-on-chronic liver injury.3 On top of a leaky gut, patients with liver cirrhosis have severe defects in the innate immune system, affecting macrophages, neutrophils and the complement system.4 The liver itself represents an important immunological organ and is the first target of gut-derived...
Source: Gut - Category: Gastroenterology Authors: Tags: Commentary Source Type: research

Related Links:

AbstractPurpose of ReviewCurrent research into the pathogenesis of cirrhosis is largely dominated by investigations of hepatocellular injury and fibrogenesis, mostly in short-term experimental models. Cirrhosis in the human evolves for decades with histologic features that are very different from the models studied, dominated by hepatic vein obstruction and congestion. This is a clue that the mechanisms operating in the human are different from those in most animal models.Recent FindingsThis paper presents an updated “vascular hypothesis” with previously unpublished observations that provide a more complete und...
Source: Current Hepatitis Reports - Category: Infectious Diseases Source Type: research
AbstractHigh levels of antimicrobial drug resistance deleteriously affecting the outcome of treatment with antibacterial agents are causing increasing concern worldwide. This is particularly worrying in patients with cirrhosis with a depressed immune system and heightened susceptibility to infection. Antibiotics have to be started early before results of microbiological culture are available. Current guidelines for the empirical choice of antibiotics in this situation are not very helpful, and embracing antimicrobial stewardship including rapid de-escalation of therapy are not sufficiently emphasised. Multi-drug resistant ...
Source: Hepatology International - Category: Infectious Diseases Source Type: research
CONCLUSIONS: Different hepatic diseases owned different intestinal bacterial characters. Microbiota can improve or aggravate three kinds of liver diseases through several mechanisms. However, the depletion of these bacteria is needed to verify their role in liver disease. PMID: 31558417 [PubMed - as supplied by publisher]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
Abstract 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 patient...
Source: World Journal of Gastroenterology - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Authors: Zaccherini G, Bernardi M Abstract Low serum albumin is common in cirrhosis and is associated with a reduced survival. Moreover, in this setting, the native isoform of albumin can be severely reduced due to several posttranscriptional changes that impair the non-oncotic properties of the molecule. Due to its oncotic power, albumin acts as a powerful plasma expander. As such, it can antagonize the consequences of effective hypovolemia deriving from the systemic hemodynamics abnormalities that characterize advanced cirrhosis. Indeed, the current established indications to the use of albumin in this context pe...
Source: Acta Gastro-Enterologica Belgica - Category: Gastroenterology Tags: Acta Gastroenterol Belg Source Type: research
The gut-liver-axis presents the pathophysiological hallmark for initiation and/or perpetuation of multiple liver diseases[1] and has been proposed to be fueled by pathological bacterial translocation (PBT) from the gut[2]. In liver cirrhosis, PBT from the gut into the liver and systemic circulation is one of the causes of bacterial infections and the augmented pro-inflammatory response to gut-derived products[2,3]. In fact, failure to control invading bacteria and bacterial products in concert with host susceptibility determines remote organ injury in liver cirrhosis.
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
AbstractThe rapidity of the increase in the global burden of liver disease covered in this review with estimates worldwide of 2 million deaths from cirrhosis and with no signs of effective controls being introduced for two of the main causes, namely, excess alcohol consumption and obesity, is of great concern. The 25% prevalence of non-alcoholic fatty liver disease in many population groups and the recent description of primary hepatocellular cancer (HCC) in obese subjects without underlying severe fibrosis/cirrhosis also raises many questions. In addition, covered in this review are more encouraging areas including techni...
Source: Hepatology International - Category: Infectious Diseases Source Type: research
Conclusion Massive SI and immune cell paralysis associated with ACLF represent the extreme severity of CAID in response to an infectious or sterile challenge. The severe immune disturbance plays a pivotal role in the pathogenesis of the distinctive features of ACLF: organ failure and bacterial infection susceptibility. Excessive SI in ACLF results from the massive activation and dysfunction of an innate immune system challenged by increased PAMPs and DAMPs. SI leads to cell and tissue immunopathology contributing to hepatic and extrahepatic organ failure. Concomitantly, the course of ACLF is associated with a disproportio...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Ali Mahzari1, Songpei Li1, Xiu Zhou1,2, Dongli Li2, Sherouk Fouda1, Majid Alhomrani1, Wala Alzahrani1, Stephen R. Robinson1 and Ji-Ming Ye1,2* 1Lipid Biology and Metabolic Disease Laboratory, School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia 2School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China The present study investigated the effects of matrine on non-alcoholic steatohepatitis (NASH) in mice induced by a methionine choline-deficient (MCD) diet and the mechanism involved. The study was performed in C57B/6J mice fed a MCD diet for 6 weeks to induce NAS...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion: In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future. Introduction Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third cause of cancer-related deaths (Jemal et al., 2011). Chronic inflammation, caused by chemical, biological and physical factors, is found to be related to certain human cancers. The effe...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
More News: Allergy & Immunology | Cirrhosis | Hospitals | Liver | Liver Disease | Translocation | Urology & Nephrology