Oral antibiotics treatment attenuates dietary induced non-alcoholic fatty liver disease
To date the role of the alterations of intestinal microbiota in the development of intestinal barrier function in settings of non-alcoholic fatty liver disease (NAFLD) has not been fully understood. Here, we assessed the effect of antibiotics on the development of NAFLD and their impact on intestinal barrier dysfunction. Male C57BL/6J mice were either pair-fed a liquid control diet (C) or fat- and fructose-rich diet (FFr) +/- antibiotics (AB, ampicillin/ vancomycin/ metronidazole/ gentamycin) for 7 weeks. Fasting blood glucose was determined and markers of liver damage, inflammation, intestinal barrier function, and microbiota composition were assessed. The development of hepatic steatosis with early signs of inflammation found in FFr-fed mice was significantly abolished in FFr-fed mice concomitantly treated with antibiotics. Also, while prevalence of bacteria in faeces was not detectable and toll-like receptor 4 (TLR4) ligand levels in portal plasma were at the level of controls in FFr-fed mice treated with AB, impairments of intestinal barrier function like an increased permeation of xylose and inducible nitric oxide synthase (iNOS) protein levels were prevalent to similar extent in both FFr-fed groups. Exposure of everted small intestinal tissues sacs of naïve mice to fructose resulted in a significant increase in tissue permeability and loss of tight junction proteins, being not affected by the presence of AB, whereas the concomitant treatment of tissue sacs with the NOS inhibitor aminoguanidine attenuated these alterations. Taken together, our data suggest that intestinal barrier dysfunction in diet-induced NAFLD in mice may not be predominantly dependent on changes in intestinal microbiota but rather that fructose-induced alterations of intestinal NO-homeostasis might be critical herein.