The Synbiotic Combination of Akkermansia muciniphila and Quercetin Ameliorates Early Obesity and NAFLD through Gut Microbiota Reshaping and Bile Acid Metabolism Modulation

Abstract

Gut microbiota plays a key role in obesity and non-alcoholic fatty liver disease (NAFLD), so synbiotics could be a therapeutic alternative. We aim to evaluate a nutritional intervention together with the administration of the bacteria <i>Akkermansia muciniphila</i> and the antioxidant quercetin in an in vivo model of early obesity and NAFLD. 21-day-old rats were fed with control or high-fat diet for six weeks. Then, all animals received control diet supplemented with/without quercetin and/or <i>A. muciniphila</i> for three weeks. Gut microbiota, NAFLD-related parameters, circulating bile acids (BAs) and liver gene expression were analyzed. The colonization with <i>A. muciniphila</i> was associated with less body fat, while synbiotic treatment caused a steatosis remission, linked to hepatic lipogenesis modulation. The synbiotic promoted higher abundance of <i>Cyanobacteria</i> and <i>Oscillospira</i>, and lower levels of <i>Actinobacteria</i>, <i>Lactococcus</i>, <i>Lactobacillus</i> and <i>Roseburia</i>. Moreover, it favored elevated unconjugated hydrophilic BAs plasma levels and enhanced hepatic expression of BA synthesis and transport genes. <i>A. muciniphila</i> correlated with circulating BAs and liver lipid and BA metabolism genes, suggesting a role of this bacterium in BA signaling. Beneficial effects of <i>A. muciniphila</i> and quercetin combination are driven by gut microbiota modulation, the shift in BAs and the gut-liver bile flow enhancement.