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Leaky Gut and Fatty Liver
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in pediatric and adult populations living in industrialized countries. NAFLD encompasses steatosis and nonalcoholic steatohepatitis (NASH), and it is characterized by perivenular and lobular inflammation. Progression to fibrosis and cirrhosis are the primary complications of NAFLD. Based on a recent meta-analysis, one in four people in Europe, the United States, and Asia have NAFLD.
The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.
2. Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in pediatric and adult populations living in industrialized countries. NAFLD encompasses steatosis and nonalcoholic steatohepatitis (NASH), and it is characterized by perivenular and lobular inflammation. Progression to fibrosis and cirrhosis are the primary complications of NAFLD . Based on a recent meta-analysis, one in four people in Europe, the United States, and Asia have NAFLD . The “multiple parallel hit” hypothesis may explain the pathogenesis and progression of NAFLD. Especially in recent years, there has been increasing interest in gut–liver axis dysfunction (dysbiosis, bacterial overgrowth, and changes in intestinal permeability) associated with the progression of NAFLD; therefore, gut–liver axis dysfunction is considered important as a possible alternative therapeutic target for patients who are unable to benefit from lifestyle changes, healthy eating, and promotion of physical activity . In NASH, chronic inflammation is triggered by hepatocyte fat accumulation, followed by exposure to inflammatory cytokines, insulin resistance, oxidative stress, lipotoxicity mainly from free fatty acids (FFAs), and gut-derived endotoxins. Here, we focused on gut-derived endotoxins and reviewed the most recent data regarding the gut–liver axis and its role in the pathogenesis and progression of NAFLD. We also reviewed experimental studies in animal models and preliminary results from several randomized clinical trials (RCTs). The objectives of our review were to (1) appraise the pathophysiology of the gut–liver axis focusing on endotoxins and (2) delineate novel therapeutic perspectives via intestinal permeability.
3. The Inflammatory State
The entry is from 10.3390/ijms22158161
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