In NALFD as well as in cirrhosis, increased intestinal permeability has been demonstrated and linked with increased inflow of bacterial products into the liver via pathological bacterial translocation. In liver cirrhosis contributing factors include reduced bile flow, diminished levels of antimicrobial peptides and changes in expression and function of tight junction proteins in the intestine.
Humans have nearly 10 trillion intestinal bacteria. This microbiome on the one hand plays a key role for metabolism and energy harvest which relates to obesity and NAFLD and on the otehr side represents the largest reservoir of antigens and bacterial products which pre-disposes to hepatic inflammation/injury mediated by increased bacterial translocation from the gut to the liver. Quantitative and qualitative alterations have been reported in the intestinal microbiome in NAFLD and also cirrhosis. In advanced cirrhosis, bacterial translocation constitutes the pathophysiological hallmark of bacterial infections such as spontaneous bacterial peritonitis, which are a major determinant of mortality. The available evidence also indicates a role for gut microbiota in the etiology of NAFLD and especially in the progression to its more advanced state. Furthermore, the absorbed toxins produced by the altered intestinal microbiome can have significant adverse effects on the liver in patients with chronic liver disease. The concept for the CARBALIVE project is outlined in the figure above.