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Nutrition and Disease

Probiotics Reduce the Inflammatory Response Induced by a High-Fat Diet in the Liver of Young Rats^1,2

³ Istituto di Ricovero e Cura a Carattere Scientifico Centro Neurolesi Bonino-Pulejo, 98124 Messina, Italy ⁴ Department of Experimental Pharmacology ⁵ Department of Pediatrics, University of Naples "Federico II", 80131 Naples, Italy ⁶ Department of Pharmaceutical Sciences, University of Salerno, 84084 Salerno, Italy ⁷ Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98125 Messina, Italy

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the pediatric population. Preliminary evidence suggests a potential therapeutic utility of probiotics for this condition. Here, we tested the potential effect of the probiotic VSL#3 (a multistrain preparation composed of Streptococcus thermophilus and several species of Lactobacillus and Bifidobacteria) on oxidative and inflammatory damage induced by a high-fat diet in the liver of young rats. At weaning, young male Sprague-Dawley rats were randomly divided into 3 groups (n = 6) fed a standard, nonpurified diet (Std; 5.5% of energy from fat) or a high-fat liquid diet (HFD; 71% of energy from fat). One of the HFD groups received by gavage VSL#3 (13 x 10⁹ bacteria·kg^–1·d^–1). After 4 wk, the HFD rats had greater body weight gain, fat mass, serum aminotransferase, and liver weight than rats fed the Std diet. The HFD induced liver lipid peroxidation, tumor necrosis factor (TNF) production, protein S-nitrosylation, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 expression, and metalloproteinase (MMP) activity. Moreover, in the HFD group, PPAR expression was less than in rats fed the Std diet. In rats fed the HFD diet and treated with VSL#3, liver TNF levels, MMP-2 and MMP-9 activities, and expression of iNOS and COX-2 were significantly lower than in the HFD group. In VSL#3-treated rats, PPAR expression was greater than in the HFD group. A modulation of the nuclear factor-B pathway by VSL#3 was also demonstrated. Our data suggest that VSL#3 administration could limit oxidative and inflammatory liver damage in patients with NAFLD.

^* To whom correspondence should be addressed. E-mail: meli{at}unina.it.

Manuscript received 30 October 2008. Initial review completed 11 November 2008. Revision accepted 22 January 2009.

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