Modulation of Gut Microbiota by Berberine Improves Steatohepatitis in High-Fat Diet-Fed BALB/C Mice

Abstract

Background: Dysbiosis of the gut microbiota underlies non-alcoholic steatohepatitis (NASH). Ingredient of Chinese herbal medicine, berberine, has been proved to regulate the gut microbiota without systemic side effects. Therefore, we explored its effects on NASH induced by high-fat diet (HFD).

Methods: BALB/c mice were randomized into three groups, including: control, model, and berberine treatment. With the exception of the control group with the standard diet, the model, and the treatment groups were treated by HFD. Mice from treatment group were further subjected to berberine (200 mg/kg/d) gavage since the 5th week. At the end of the 13th week, gut bacteria, liver endotoxin receptor, and inflammation cytokines were assessed by real-time PCR. NASH and its predisposing factors were evaluated biochemically and pathologically.

Results: Compared to their decreases in the model group, berberine administration restored the relative level of Bifidobacteria (2.16 ± 0.63 vs. 0.50 ± 0.08, P < 0.01) and the ratio of Bacteroidetes/ Firmicutes (0.76 ± 0.26 vs. 0.39 ± 0.11, P < 0.01), respectively, in the treatment groups. Microbiota restoration led to significant reductions in body weight, serum levels of lipids, glucose, insulin, and homeostasis model assessment of insulin resistance. Improvements were also observed in the serum transaminase activity and nonalcoholic fatty liver disease activity score, which demonstrated the attenuation of NASH. Mechanically, expression levels of CD14, IL-1, IL-6 and TNF-α were statistically down-regulated (treatment group vs model group, P < 0.01).

Conclusions: Berberine alleviates NASH and its predisposing factors. Normalization of gut microbiota might underlie its effect.