Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice

PLoS One. 2014 Jan 27;9(1):e80169. doi: 10.1371/journal.pone.0080169. eCollection 2014.


Objective: Experimental 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.

Methods: Experimental 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 5×10(7) 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.

Results: LGG 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.

Conclusions: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / metabolism
  • Analysis of Variance
  • Animals
  • Caco-2 Cells
  • DNA Primers / genetics
  • Dextrans / metabolism
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / prevention & control*
  • Fructose / administration & dosage
  • Fructose / adverse effects
  • Humans
  • Immunohistochemistry
  • Intestine, Small / metabolism
  • Lactobacillus rhamnosus*
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease
  • Permeability
  • Probiotics / pharmacology*
  • Probiotics / therapeutic use
  • Real-Time Polymerase Chain Reaction


  • DNA Primers
  • Dextrans
  • Fructose
  • Alanine Transaminase

Grant support

This work was supported by grants from the Competence Network of Obesity, group ‘Obesity and GI tract’, funded by the Federal Ministry of Education and Research (FKZ: 01GI0843) to S. C. Bischoff and the Institute Danone research grant 2010 to Y. Ritze. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.