lipoteichoic-acid and Liver-Diseases

Gut microbiota and the mammalian host share a symbiotic relationship, in which the host provides a suitable ecosystem for the gut bacteria to digest indigestible nutrients and produce useful metabolites. Although gut microbiota primarily reside in and influence the intestine, they also regulate liver function via absorption and subsequent transfer of microbial components and metabolites through the portal vein to the liver. Due to this transfer, the liver may be continuously exposed to gut-derived metabolites and components. For example, short-chain fatty acids (SCFA) produced by gut microbiota, through the fermentation of dietary fiber, can suppress inflammation via regulatory T cell induction through SCFA-induced epigenetic mechanisms. Additionally, secondary bile acids (BA), such as deoxycholic acid, produced by gut bacteria through the 7α-dehydroxylation of primary BAs, are thought to induce DNA damage and contribute to the remodeling of tumor microenvironments. Other substances that are also thought to influence liver function include lipopolysaccharides (components of the outer membrane of gram-negative bacteria) and lipoteichoic acid (cell wall component of Gram-positive bacteria), which are ligands of innate immune receptors, Toll-like receptor-4, and Toll-like receptor-2, respectively, through which inflammatory signaling is elicited. In this review, we focus on the role of gut microbiota in the liver microenvironment, describing the anatomy of the gut-liver axis, the role of gut microbial metabolites, and the relationships that exist between gut microbiota and liver diseases, including liver cancer.

Topics: Bile Acids and Salts; Carcinoma, Hepatocellular; Cellular Senescence; Choline; DNA Damage; Ethanol; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gram-Positive Bacteria; Hepatitis, Alcoholic; Humans; Lipopolysaccharides; Liver; Liver Diseases; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Symbiosis; Teichoic Acids; Tumor Microenvironment

Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.

Topics: Animals; Complement Activation; Escherichia coli; Hemodynamics; Interleukin-1; Leukocytes, Mononuclear; Lipopolysaccharides; Liver Diseases; Necrosis; Rabbits; Shock; Staphylococcus epidermidis; Teichoic Acids; Tumor Necrosis Factor-alpha

Regimens of intravenous injections of saline-washed Lactobacillus fermentum elicited hypersensitivity reactions in rabbits. Pathological investigation revealed evidence consistent with induction of aggregate anaphylaxis, characterised by acute cor pulmonale. Additional evidence of similar tissue injury was observed in livers of rabbits which had received several intravenous injections of L. fermentum. Deposition of immune complexes in kidney glomeruli was demonstrated in only 1 out of 11 animals. Skin testing experiments revealed that lipoteichoic acid was involved in type I and type II antibody-mediated hypersensitive states. The involvement of bacterial cell surface components and extracellular products in such reactions implies a potential role in host tissue injury.

Topics: Animals; Hypersensitivity; Kidney Glomerulus; Lactobacillus; Lipopolysaccharides; Liver Diseases; Lung Diseases; Male; Phosphatidic Acids; Rabbits; Teichoic Acids; Vasculitis