Abstract
ObjectiveExperimental evidence revealed that obesity-associated non-alcoholic fatty liver disease (NAFLD) is linked to changes in intestinal permeability and translocation of bacterial products to the liver. Hitherto, no reliable therapy is available except for weight reduction. Within this study, we examined the possible effect of the probiotic bacterial strain Lactobacillus rhamnosus GG (LGG) as protective agent against experimental NAFLD in a mouse model.MethodsExperimental NAFLD was induced by a high-fructose diet over eight weeks in C57BL/J6 mice. Fructose was administered via the drinking water containing 30% fructose with or without LGG at a concentration resulting in approximately 5×107 colony forming units/g body weight. Mice were examined for changes in small intestinal microbiota, gut barrier function, lipopolysaccharide (LPS) concentrations in the portal vein, liver inflammation and fat accumulation in the liver.ResultsLGG increased beneficial bacteria in the distal small intestine. Moreover, LGG reduced duodenal IκB protein levels and restored the duodenal tight junction protein concentration. Portal LPS (P≤0.05) was reduced and tended to attenuate TNF-α, IL-8R and IL-1β mRNA expression in the liver feeding a high-fructose diet supplemented with LGG. Furthermore liver fat accumulation and portal alanine-aminotransferase concentrations (P≤0.05) were attenuated in mice fed the high-fructose diet and LGG.ConclusionsWe show for the first time that LGG protects mice from NAFLD induced by a high-fructose diet. The underlying mechanisms of protection likely involve an increase of beneficial bacteria, restoration of gut barrier function and subsequent attenuation of liver inflammation and steatosis.
Highlights
Over the last decades, progress was made in understanding the relationship between non-alcoholic fatty liver disease (NAFLD) and the intestinal microbiota [1,2,3]
We investigated the role of the probiotic Lactobacillus rhamnosus GG (LGG) on the development of NAFLD in mice fed a control diet or a highfructose diet regarding total caloric intake from food and fructose intake
We found an increased expression of carbohydrate-responsive element-binding protein (ChREBP), acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) feeding the fructose rich diet that was significantly reduced after LGG supplementation (Fig. 2A,B,C)
Summary
Progress was made in understanding the relationship between non-alcoholic fatty liver disease (NAFLD) and the intestinal microbiota [1,2,3]. Two major risk factors for NAFLD have been clearly identified - obesity and diabetes - both associated with changes in the intestinal microbiota [4], and with small intestinal bacterial overgrowth [5]. Understanding how the microbiota contributes to the pathology of diet-induced NAFLD remains a major challenge [8]. Patients with NAFLD are characterized by a high prevalence of obesity ranging from 30% to 100% [11]. About 20% of patients with steatosis develop a non-alcoholic steatohepatitis that may lead to severe hepatic and systemic diseases as well as increased mortality [13]
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