Administration Of Gut Bacteria Expressing N-Acyl Phosphatidylethanolamine Reduces Steatohepatitis In Ldlr-/- Mice Fed A Western Diet

Background: The rise in obesity in the United States has led to a concomitant rise in prevalence of non-alcoholic fatty liver disease (NAFLD). The four stages of NAFLD include accumulation of triglyceride (hepatosteatosis), development of chronic inflammation (non-alcoholic steatohepatitis, NASH), fibrosis, and finally cirrhosis. Unlike wildtype C57BL6 mice, low density lipoprotein receptor (LDLR) -/- mouse fed a diet enriched in fat and cholesterol (Western Diet) progress to NASH and fibrotic stages of NAFLD. We showed that incorporating engineered bacteria expressing N-acyl phosphatidylethanolamine (NAPE) into the gut microbiota can inhibit development of obesity. NAPE is a precursor of N-acylethanolamines, which are bioactive lipids with anti-inflammatory functions. Here, we test the hypothesis that administering these NAPE-expressing bacteria inhibits development of NASH and fibrosis. Methods: NAPE-expressing E. coli Nissle 1917 (pNAPE-EcN, n=10), control Nissle 1917 (pEcN, n=10), or vehicle (veh, n=10) were given via drinking water to LDLR -/- mice fed a Western diet for 12 weeks. LDLR -/- mice fed a low fat diet (LFD) (n=10) were included for comparison. Results: pNAPE-EcN reduced adiposity by 26% compared with pEcN and veh (P Conclusions: Our results demonstrate that incorporating therapeutically modified bacteria into the gut microbiota has potential to inhibit the development of NAFLD.