Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging Roseburia, Streptococcus, and Rothia. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.

Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.

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