The Molecular and Mechanistic Insights Based on Gut-Liver Axis: Nutritional Target for Non-Alcoholic Fatty Liver Disease (NAFLD) Improvement

Abstract

Non-alcoholic fatty liver disease (NAFLD) is recognized as the most frequent classification of liver disease around the globe. Along with the sequencing technologies, gut microbiota has been regarded as a vital factor for the maintenance of human and animal health and the mediation of multiple diseases. The modulation of gut microbiota as a mechanism affecting the pathogenesis of NAFLD is becoming a growing area of concern. Recent advances in the communication between gut and hepatic tissue pave novel ways to better explain the molecular mechanisms regarding the pathological physiology of NAFLD. In this review, we recapitulate the current knowledge of the mechanisms correlated with the development and progression of NAFLD regulated by the gut microbiome and gut-liver axis, which may provide crucial therapeutic strategies for NAFLD. These mechanisms predominantly involve: (1) the alteration in gut microbiome profile; (2) the effects of components and metabolites from gut bacteria (e.g., lipopolysaccharides (LPS), trimethylamine-N-oxide (TMAO), and N,N,N-trimethyl-5-aminovaleric acid (TMAVA)); and (3) the impairment of intestinal barrier function and bile acid homeostasis. In particular, the prevention and therapy of NAFLD assisted by nutritional strategies are highlighted, including probiotics, functional oligosaccharides, dietary fibers, ω-3 polyunsaturated fatty acids, functional amino acids (L-tryptophan and L-glutamine), carotenoids, and polyphenols, based on the targets excavated from the gut-liver axis.

Keywords: barrier function; gut microbiota; gut–liver axis; liver disease; nutrition.

Figure 1

Non-alcoholic fatty liver disease (NAFLD) induced by unbalanced diet and its nutritional improvement strategies based on the gut–liver axis. Long-term high-saturated fat or high-fructose diet leads to an imbalanced intestinal flora, which in turn elicits an impaired gut barrier function and increased permeability, followed by bacterial translocation (BT), and additional bacterial components and metabolites (e.g., lipopolysaccharides (LPS), trimethylamine (TMA), N,N,N-trimethyl-5-aminovaleric acid (TMAVA), and endogenous ethanol (EE)) entering into the liver through the portal vein. NAFLD patients exhibit abnormal bile acids (BAs) metabolism and its related signaling pathways. These factors together accelerate the occurrence and progression of NAFLD. By contrast, an appropriate consumption of probiotics, functional oligosaccharides, dietary fibers, ω-3 polyunsaturated fatty acids (ω-3 PUFAs), functional amino acids (L-tryptophan and L-glutamine), carotenoids, and polyphenols, contributes (1) to the maintenance of the homeostasis of the intestinal flora and BAs, (2) to the enhancement of the intestinal barrier integrity, and (3) to the production of salutary metabolites (e.g., short chain fatty acids (SCFAs), indoles, and urolithins), thereby supporting a healthy liver.