The role of intestinal microbiota in the pathogenesis of NAFLD: starting points for intervention

In recent years, close links between intestinal microbiota and host metabolismhave been recognized. Intestinal bacteria can participate in the extraction ofcalories from food, and circulation of bacterial products, in particular lipopolysaccharides(LPS), is responsible for the “metabolic endotoxemia”, whichcontributes to insulin resistance and its complications, such as non-alcoholicfatty liver disease (NAFLD). Indeed, qualitative and quantitative intestinal dysbioticchanges have been clearly documented in NAFLD patients, and severalmechanisms by which the intestinal microbiota can directly promote liver fatdeposition, inflammation and fibrosis have also been described. Consistently,although with some differences concerning type and proportion of results,experimental and clinical studies are quite concordant in demonstrating beneficialeffects of probiotic and/or prebiotic therapy in NAFLD. Although somephysiopathological bases have been produced, major doubts still remain concerninghow and when to intervene. Indeed, most of the available works wereperformed with mixtures of probiotics and/or prebiotics, and a baseline assessmentof dysbiosis aimed at selecting the best candidates for treatmentand predicting response has not been performed in any of the clinical studiesin NAFLD. While future research is expected to solve these issues, the particularlyfavorable safety profile suggests that probiotic/prebiotic therapy couldalready be “tested” in NAFLD patients on an individual basis, at least once allthe measures recommended by the latest guidelines have failed.