The Influence of Gut Microbial Metabolism on the Development and Progression of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of excess fat in the liver parenchyma in the absence of excess alcohol consumption and overt inflammation. It has also been described as the hepatic manifestation of metabolic syndrome (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). The incidence of NAFLD has been reported to be 43-60% in diabetics, ~90% in patients with hyperlipidemia and 91% in morbidly obese patients (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015, Machado M, Marques-Vidal P, Cortez-Pinto H, J Hepatol, 45:600-606, 2006, Vernon G, Baranova A, Younossi ZM, Aliment Pharmacol Ther, 34:274-285, 2011). The risk factors that have been associated with the development of NAFLD include male gender, increasing age, obesity, insulin resistance, diabetes and hyperlipidemia (Attar BM, Van Thiel DH, Sci World J, 2013:481893, 2013, Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A, Forum Nutr, 5:1544-1460, 2013). All of these risk factors have been linked to alterations of the gut microbiota, ie., gut dysbiosis (He X, Ji G, Jia W, Li H, Int J Mol Sci, 17:300, 2016). However, it must be pointed out that the prevalence of NAFLD in normal weight individuals without metabolic risk factors is ~16% (Than NN, Newsome PN, Atherosclerosis. 239:192-202, 2015). This fact has led some investigators to hypothesize that the gut microbiota can impact lipid metabolism in the liver independently of obesity-related metabolic factors (Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold g, et al., Gut, 65:330 339, 2016) (Le Roy T, Llopis M, Lepage P, Bruneau A, Rabot S, Bevilacqua C, et al., Gut, 62:1787-1794, 2013). In this chapter, we will explore the effect of the gut microbiota on hepatic lipid metabolism and how this affects the development of NAFLD.