Genetically encoded probiotic EcN 1917 alleviates alcohol-induced acute liver injury and restore gut microbiota homeostasis

Abstract

Alcohol abuse increases the risk of acute liver injury. Escherichia coli Nissle 1917(EcN) has been comprehensively demonstrated as a safe oral probiotic. In this study, we genetically modified EcN expressing alcohol dehydrogenase gene, acetaldehyde dehydrogenase gene, NAD synthase gene, and NADH oxidase gene. Applied strains in the mouse experiment showed a 54.44% reduction in serum ethanol. EcN-treated mice also exhibited lower liver AST, ALT, MDA, TG, T-CHO, TNF-α, IL-1β and increased SOD and GSH levels versus untreated ones, indicating restored liver function alongside depressed oxidative stress, lipid peroxidation, and inflammation. Consistently, aberrant gene expression correlating with alcohol metabolism and injured liver induced by alcoholic food were restored following EcN inoculation. The efficacy EcN conferred was accompanied by the restoration of gut microbiota homeostasis. In conclusion, the engineered EcN has been shown to detoxify ethanol metabolites in liver disease models and which may be attributed to intestinal recovery.

Keywords

• Synthetic biology
• Alcohol dehydrogenase
• Aldehyde dehydrogenase
• Alcohol detoxification