Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice.
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.
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Yvonne
Y
Ritze
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Gyöngyi
G
Bárdos
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Anke
A
Claus
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Veronika
V
Ehrmann
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany ; Department of Nutritional Science, Friedrich-Schiller-University, Jena, Germany.
Ina
I
Bergheim
MVZ Institute of Microecology, Herborn, Germany.
Andreas
A
Schwiertz
Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
Stephan C
SC
Bischoff
D000410:Alanine Transaminase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D018938:Caco-2 Cells; D017931:DNA Primers / Q000235:genetics; D003911:Dextrans / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D010539:Permeability; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use; D060888:Real-Time Polymerase Chain Reaction
D017931:DNA Primers; D003911:Dextrans; D005632:Fructose; D000410:Alanine Transaminase