Non-alcoholic fatty liver disease (NAFLD) and its advanced stage, non-alcoholic steatohepatitis (NASH), are the most common causes of chronic liver disease in the United States. NASH features the metabolic syndrome, inflammation, and fibrosis. Probiotics exhibit immunoregulatory and anti-inflammatory activity. We tested the hypothesis that probiotic VSL#3 may ameliorate the methionine-choline-defficient (MCD) diet-induced mouse model of NASH. MCD diet resulted in NASH in C57Bl6 mice compared to methionine-choline supplemented (MCS) diet feeding evidenced by liver steatosis, increased triglycerides, inflammatory cell accumulation, increased TNFα, and fibrosis. VSL#3 failed to prevent MCD-induced liver steatosis or inflammation. MCD diet, even in the presence of VSL#3, induced upregulation of serum endotoxin and expression the TLR4 signaling components, including CD14 and MD2, MyD88 adaptor, and NF-κB activation. In contrast, VSL#3 treatment ameliorated MCD diet-induced liver fibrosis resulting in diminished accumulation of collagen and α-SMA. We identified increased expression of liver PPARs and decreased expression of pro-collagen and matrix metalloproteinases in mice fed MCD+VSL#3 compared to MCD diet alone. MCD diet triggered up-regulation of TGFβ, a known pro-fibrotic agent. In the presence of VSL#3 the MCD diet-induced expression of TGFβ was maintained, however, the expression of Bambi, a TGFβ pseudoreceptor with negative regulatory function, was increased. In summary, our data indicate that VSL#3 modulates liver fibrosis but does not protect from inflammation and steatosis in NASH. The mechanisms of VSL#3-mediated protection from MCD diet-induced liver fibrosis likely include modulation of collagen expression and impaired TGFβ signaling owed to modulation of TGFβ signaling.

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Following publication of the above article, the authors noticed that the first author's name was presented incorrectly. The author's name should have appeared as MF Rubin de Celis. The publisher regrets the error.

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