title: 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.
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China, Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China. leimingxu@yahoo.com.cn.
authors.forename: Lei-Ming
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China, Department of Pediatric Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. fattyliver2004@126.com.
authors.forename: Jian-Gao
authors.initials: JG
authors.lastname: Fan
mesh_terms: D000818:Animals; D001599:Berberine / Q000008:administration & dosage*; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D041981:Gastrointestinal Tract / Q000382:microbiology; D007333:Insulin Resistance; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000382:microbiology; D011971:Receptors, Immunologic / Q000378:metabolism
chemical_list: D016207:Cytokines; D011971:Receptors, Immunologic; C048071:endotoxin receptor; D001599:Berberine