Microbiota and gut-liver axis: their influences on obesity and obesity-related liver disease

Abstract

A specific bacterial gut microbiota profile with increased extraction of energy has recently been associated with obesity, which has been shown to be a transmissible phenotype by microbiota transplantation. At the same time, there is now increasing evidence that gut microbiota plays a role in the development of hepatic steatosis and its progression to nonalcoholic steatohepatitis. This review summarizes well known and unexpected interacting factors leading to obesity and its related hepatic diseases, including intestinal mucosal permeability and its regulation, gut microbiota and translocation of its biological products, and gut-associated lymphoid tissue. These intestinal factors dictate also the balance between tolerance and immune response, which are critical for most of the complications in near and far organs or systems. We review novel mechanisms involving the development of gut permeability and adipose tissue plasticity, for example, the cross-talk between the gut microbiota, lipopolysaccharide, high-fat diet, and the endocannabinoid system tone, which have not been fully explored. Interactions between gut microbiota and other factors (eg, inflammasome deficiency) also are reviewed as emerging but far from being completely elucidated mechanisms influencing the onset of obesity and nonalcoholic fatty liver disease.

Figure 1

Events leading to bacterial and bacterial-products translocation from gut lumen to portal circulation in presence of microvillar dysfunction/leaky gut, small intestinal bacterial overgrowth (SIBO) or gut dysbiosis, stress, fat diet. Note malfunction of Tight Junctions (TJ) as one of the critical events.

Figure 2

Some conditions where gut microbiota has been implicated outside gastrointestinal tract (7).

Figure 3

Several mechanisms by which intestinal bacteria may interact on near and far organs or systems. Gut microbiota may be implicated in the pathogenesis of obesity, diabetes and nonalcoholic fatty liver disease. Gut dysbiosis is associated with an induction of TLR-4 in NAFLD patients that causes hepatic fibrogenesis and systemic inflammation. Gut microbiota interferes with FFA oxidation and uptake via PGC1-α and FIAF changes. Gut bacteria produce isomers of CLA which reduce the expression of proinflammatory cytokines and increase intestinal content of EPA and DHA . Microbiota also converts nondigestible carbohydrates into monosaccharides determining the activation of ChREBP and SREPB-1c transcription that promote hepatic lipogenesis. Properties of bile acids which have a bacteriostatic activity are modified, as well. Modified from (19). Abbreviations: EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; ChREBP/SREBP, carbohydrate- responsive element -binding protein; SREPB-1c Sterolresponsive element-binding protein 1c; CLA, conjugated linoleic acid ; FFA, free fatty acids; FIAF, fasting-induced adipose factor; LPL, lipoprotein lipase; LPS, lipopolysaccharide; PGC1-α, peroxisomal proliferator-activated receptor coactivator 1α; T2DM, Type 2 Diabetes Mellitus; TLR-4, toll like receptor 4.