Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathological hepatic conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC). Due to the epidemic obesity, NAFLD is representing a global health issue and the leading cause of liver damage worldwide. The pathogenesis of NAFLD is closely related to insulin resistance (IR), adiposity and physical inactivity as well as genetic and epigenetic factors corroborate to the development and progression of hepatic steatosis and liver injury. Emerging evidence has outlined the implication of gut microbiota and gut-derived endotoxins as actively contributors to NAFLD pathophysiology probably due to the tight anatomo-functional crosstalk between the gut and the liver. Obesity, nutrition and environmental factors might alter intestinal permeability producing a favorable micro-environment for bacterial overgrowth, mucosal inflammation and translocation of both invasive pathogens and harmful byproducts, which, in turn, influence hepatic fat composition and exacerbated pro-inflammatory and fibrotic processes. To date, no therapeutic interventions are available for NAFLD prevention and management, except for modifications in lifestyle, diet and physical exercise even though they show discouraging results due to the poor compliance of patients. The premise of this review is to discuss the role of gut–liver axis in NAFLD and emphasize the beneficial effects of probiotics on gut microbiota composition as a novel attractive therapeutic strategy to introduce in clinical practice.
Highlights
The global burden of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disorders represents a major concern for public health
Upon arrival to the liver via portal vein, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs) and high levels of free fatty hepatocytes, Kupffer cells and hepatic stellate cells (HSCs) through Toll-like receptors (TLRs) cascade, acids (FFAs) activate inflammatory response in hepatocytes, Kupffer cells and hepatic stellate cells which enhances the release of cytokines and chemokines and (HSCs) through Toll-like receptors (TLRs) cascade, which enhances the release of cytokines and worsens liver damage. (B) Probiotics may restore intestinal barrier integrity, positively acting on ZO-1 chemokines and worsens liver damage. (B) Probiotics may expression, mucus thickness and commensal bacteria proportion
Lepob/ob and Lepdb/db livers chronically exposed to LPS showed a pro-inflammatory and pro-fibrotic phenotype compared to HSCs isolated from lean mice, supporting that increased intestinal permeability may participate to the development and progression of obesity-related nonalcoholic steatohepatitis (NASH) [96]
Summary
The global burden of nonalcoholic fatty liver disease (NAFLD) as the leading cause of chronic liver disorders represents a major concern for public health. Liver biopsy remains the gold standard procedure for diagnosis of NASH and no medications have been approved for the treatment of NAFLD patients except for modifications in lifestyle, nutrition and physical exercise and weight loss [16,17]. For this reason, this review aimed to focus on the relevance of gut microbiota dysregulation in the development and progression of NAFLD and its pivotal role as non-invasive biomarkers and therapeutic target in the tailored NAFLD clinical management. We will highlight the use of probiotics, emphasizing their beneficial effects on dysbiosis as a potential therapeutic approach to introduce in clinical practice
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