The Gordian Knot of dysbiosis, obesity and NAFLD.

The development of obesity and NAFLD is known to be determined by host genetics, diet and lack of exercise. In addition, the gut microbiota has been identified to influence the development of both obesity and NAFLD. Evidence for the role of the gut microbiota has been shown by preclinical studies of transfer of gut microbiota from lean and obese individuals, with the recipient developing the metabolic features of the donor. Many bidirectional interactions of the gut microbiota, including with food, bile and the intestinal epithelium, have been identified. These interactions might contribute to the distinct steps in the progression from lean to obese states, and to steatosis, steatohepatitis and eventually fibrosis. The predominant steps are efficient caloric extraction from the diet, intestinal epithelial damage and greater entry of bacterial components into the portal circulation. These steps result in activation of the innate immune system, liver inflammation and fibrosis. Fortunately, therapeutic interventions might not require a full understanding of these complex interactions. Although antibiotics are too unselective in their action, probiotics have shown efficacy in reversing obesity and NASH in experimental systems, and are under investigation in humans.