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

Abstract

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 10(9) bacteria x kg(-1) x 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 (TNFalpha) production, protein S-nitrosylation, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 expression, and metalloproteinase (MMP) activity. Moreover, in the HFD group, PPARalpha expression was less than in rats fed the Std diet. In rats fed the HFD diet and treated with VSL#3, liver TNFalpha 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, PPARalpha expression was greater than in the HFD group. A modulation of the nuclear factor-kappaB 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.

Gut microbiome and nonalcoholic fatty liver diseases

“…With several rodent NAFLD models, a probiotic mixture VSL#3 (containing Streptococcus, Bifidobacterium, and Lactobacillus) improved liver histology, reduced liver fat, and decreased serum ALT levels (70)(71)(72)(73). With the MCDD mouse model, VSL#3 reduced liver fibrosis but aggravated liver fat and serum ALT (74).…”

Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review

“…Furthermore, there is evidence that hepatic inflammation can be reduced by means of changes to the gut microbiota induced by antibiotics and probiotics. [47][48][49][50][51][52][53][54][55][56] Under high levels of oxidative stress, which is a feature usu- …”

Probiotics as an emerging therapeutic strategy to treat NAFLD: focus on molecular and biochemical mechanisms

“…Loss or reduction of PPARα expression, in KO mice or in animal fed a methionine-choline-deficient diet or a high-fat diet (HFD), both result in hepatic steatosis [39][40][41]. In nutritional NAFLD models, the administration of a potent PPARα agonist or probiotics is found to improve the hepatic steatosis.…”