Functional Interactions between Gut Microbiota Transplantation, Quercetin and High Fat Diet Determine Non-Alcoholic Fatty Liver Disease Development in Germ-Free Mice.

SCOPE: Modulation of intestinal microbiota has emerged as a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). Here we addressed whether gut microbiota modulation by quercetin and intestinal microbiota transplantation can influence NAFLD development.

METHODS AND RESULTS: Gut microbiota donor mice were selected according to their response to high fat diet (HFD) and quercetin in terms of obesity and NAFLD-related biomarkers. Germ-free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, we identified that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin resulted in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut-liver axis alteration blockage in these receivers. Gut microbiota from the HFD-responder donor predisposed to NAFLD in transplanted germ-free mice. Divergent protective and deleterious metabolic phenotypes exhibited were related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity-associated NAFLD development.

CONCLUSIONS: Our results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as protective strategy against the development of obesity-related NAFLD. This article is protected by copyright. All rights reserved.