What are the key points in the association between the gut microbiome and nonalcoholic fatty liver disease?

Abstract

Approximately 25% of the adult population inWestern countries has fatty liver disease, in the absence of excessive alcohol consumption, a condition known as nonalcoholic fatty liver disease (NAFLD). NAFLD is the result of triglyceride accumulation in the hepatocyte and is considered to be the hepatic component of the metabolic syndrome [1]. It is closely related to obesity, insulin resistance and type 2 diabetes mellitus, representing one of the leading causes of chronic liver disease worldwide and the third leading cause of hepatocellular carcinoma. The term NAFLD encompasses different states of disease activity, ranging from steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma [1]. The humanmicrobiome consists of the genetic context of bacteria, archaea, viruses and eukaryotic microbes that reside throughout the human body. However, practically the gut microbiome refers to the > 1014 bacteria inhabiting the human intestine. Healthy adults harbor more than 1000 species of bacteria, among which Bacteroidetes and Firmicutes are the most prevalent [2]. These microorganisms, which are implicated in various metabolic activities, protect against pathogens and educate the innate system, thus contributing to health or disease, as characterized by homeostasis or dysbiosis, respectively [3]. The liver and the gut are metabolically interconnected. Therefore, any dysfunction in the gut-liver axis, such as increased intestine permeability and dysbiosis are associated with NAFLD. NAFLD has been documented to be transmissible after fecal transplantation of the gut microbiome into recipient mice. Also, many animal and human studies have demonstrated the presence of gut dysbiosis in NAFLD. However, findings are conflicting regarding the observed differences in bacterial taxonomic composition amongst various studies. These discrepancies may be due to differences in the: 1) design of the study; 2) studied ethnic groups; 3) studied geographical areas (Asia, Europe, North America); 4) age of patients, i.e. adults versus children; 5) sample size; 6) laboratory methodologies analyzing gut microbiome as well as 7) the