Gut-liver Axis and Microbiota in NAFLD: Insight Pathophysiology for Novel Therapeutic Target

Abstract

There is increasing evidence for a correlation between intestinal microbiota, bacterial translocation and hepatic steatosis. Intestinal microbiota affects nutrient absorption and energy homeostasis. Altered intestinal permeability may favor the passage of bacteriaderived compounds into systemic circulation, causing a systemic inflammatory state, characteristic of the metabolic syndrome. The interaction between intestinal permeability and luminal bacteria is involved in the pathogenesis and evolution of non-alcoholic liver disease. Microbiota pharmacological modulation could be a promising tool for a new therapeutical approach to non-alcoholic fatty liver disease.

A composite model including visfatin, tissue polypeptide-specific antigen, hyaluronic acid , and hematological variables for the diagnosis of moderate-to-severe fibrosis in nonalcoholic fatty liver disease: a preliminary study

“…14,15 It has been postulated that gut microflora participates in the pathogenesis of obesity and NAFLD by damaging the intestinal mucosal barrier. 16 Moreover, some bacterial species produce small amounts of alcohol entering the portal venous system. Intercellular tight junctions are the key structures regulating paracellular trafficking of macromolecules, and zonulin is one of the physiological mediators of this process.…”

LPS Regulates Apolipoprotein E and A<i>β</i> Interactionswith Effects on Acute Phase Proteins and Amyloidosis

“…Monitoring dietary fat intake to reduce LPS has become important to metabolic diseases and neurodegenerative diseases such as Parkinson's disease [26] [38]- [41]. In obese mice altered inflammatory responses were found with LPS administration when compared with control mice with intestinal microbiota and NAFLD closely linked with connections to the systemic inflammation and the metabolic syndrome [42]- [45]. LPS effects on the release of alpha-synuclein [4] from cells in the periphery link the endotoxin to peripheral alpha-synuclein homeostasis (Figure 2) and to cholesterol metabolism with relevance to PD and AD [4].…”

Nonalcoholic fatty liver disease as trigger of cardiovascular and metabolic complication in metabolic syndrome

“…SNPs have been found in genes encoding for: the manganese superoxide dismutase (SOD2) regulating mitochondrial import and anti-oxidant activity [18]; the transcription factor Kruppel-like factor 6 (KLF6) regulating metabolism in hepatocytes and fibro genesis in hepatic stellate cells [19]; and the lipin-1 regulating the flux of free fatty acids between the adipose tissue and the liver whose expression is deregulated during steatosis [22]. Finally, there is a growing awareness that phenotypic expression of some genetic variants may be age-related.…”

“…Such multiple pathogenesis factors may include oxidative damage, unregulated hepatocyte apoptosis, activation of the profibrogenic transforming growth factor (TGF)-beta pathway, deregulation of multiple adipokines and hepatic stellate cell activation [21]. An increased intestinal permeability in NAFLD patients may alter the gut-liver balance contributing to the activation of the inflammatory cascade in the liver, thus enhancing the progression of the disease to NASH [22,23].…”

“…NAFLD is associated with increased intestinal permeability (IP), and overgrowth of small bowel bacteria (SIBO) [22,24]. In in vitro and animal models of NAFLD, increased IP, and alterations of gut microbiota have been shown to increase the exposure of the liver to gut-derived bacterial products [such as lipopolysaccharides (LPS)], which may cause low-grade endotoxemia in the portal system [24].…”