Dr. Bray Links

Thursday, December 3, 2015

Gut microbiota and host metabolism in liver cirrhosis

The gut microbiota has the capacity to produce a diverse range of compounds that play a major role in regulating the activity of distal organs and the liver is strategically positioned downstream of the gut. Gut microbiota linked compounds such as short chain fatty acids, bile acids, choline metabolites, indole derivatives, vitamins, polyamines, lipids, neurotransmitters and neuroactive compounds, and hypothalamic-pituitary-adrenal axis hormones have many biological functions. This review focuses on the gut microbiota and host metabolism in liver cirrhosis. Dysbiosis in liver cirrhosis causes serious complications, such as bacteremia and hepatic encephalopathy, accompanied by small intestinal bacterial overgrowth and increased intestinal permeability. Gut dysbiosis in cirrhosis and intervention with probiotics and synbiotics in a clinical setting is reviewed and evaluated. Recent studies have revealed the relationship between gut microbiota and host metabolism in chronic metabolic liver disease, especially, non-alcoholic fatty liver disease, alcoholic liver disease, and with the gut microbiota metabolic interactions in dysbiosis related metabolic diseases such as diabetes and obesity. Recently, our understanding of the relationship between the gut and liver and how this regulates systemic metabolic changes in liver cirrhosis has increased. The serum lipid levels of phospholipids, free fatty acids, polyunsaturated fatty acids, especially, eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid have significant correlations with specific fecal flora in liver cirrhosis. Many clinical and experimental reports support the relationship between fatty acid metabolism and gut-microbiota. Various blood metabolome such as cytokines, amino acids, and vitamins are correlated with gut microbiota in probiotics-treated liver cirrhosis patients. The future evaluation of the gut-microbiota-liver metabolic network and the intervention of these relationships using probiotics, synbiotics, and prebiotics, with sufficient nutrition could aid the development of treatments and prevention for liver cirrhosis patients.

An increasing amount of recent evidence has demonstrated that several diseases, such as irritable bowel syndrome, inflammatory bowel disease, diabetes, allergy, cancer, obesity, autism and liver disease, are related to alterations in intestinal microbiota (known as dysbiosis). Gut-derived complications in liver cirrhosis such as small intestinal bacterial overgrowth and increased intestinal permeability (leaky gut), resulting in bacterial or endotoxin translocation-related systemic disorders such as spontaneous bacterial peritonitis, hyperdynamic state, portal hypertension, hepatorenal syndrome, hepatic encephalopathy, and multiple organ failure, have been reported in clinical settings. Different etiologies of liver cirrhosis, including viral hepatitis, alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD), have different gut microbiota and mechanisms of developing liver fibrosis. Furthermore, each disease has a different hepatic metabolism, suggesting further development in this research area. However, there have been few reports of correlations between gut microbiota and host metabolism in cirrhotic patients. This review will discuss (1) the relationship between gut microbiota and host metabolism in general; (2) the results of intervention for liver cirrhosis by probiotics; and (3) gut-microbiota and host metabolism in cirrhosis and the use of systems biology as a tool for analysis.


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